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LFS
MCID: LFR001
MIFTS: 72

Li-Fraumeni Syndrome (LFS)

Categories: Bone diseases, Cancer diseases, Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Li-Fraumeni Syndrome

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MalaCards integrated aliases for Li-Fraumeni Syndrome:

Name: Li-Fraumeni Syndrome 56 12 74 24 52 25 58 73 36 29 13 54 6 43 15 71
Sarcoma Family Syndrome of Li and Fraumeni 56 52 25 73
Sbla Syndrome 56 12 52 25
Lfs 56 25 73
Sarcoma, Breast, Leukemia, and Adrenal Gland Syndrome 25
Sarcoma, Breast, Leukaemia and Adrenal Gland Syndrome 12
Li-Fraumeni Familiar Cancer Susceptibility Syndrome 12
Sbla Syndrome Li-Fraumeni-Like Syndrome 73
Li-Fraumeni Syndrome 1 71
Li Fraumeni Syndrome 52
Lfs1 52
Lfl 73

Characteristics:

Orphanet epidemiological data:

58
li-fraumeni syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (United Kingdom),1-9/100000 (United States); Age of onset: All ages; Age of death: any age;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
increased risk of developing multiple primary cancers
early age of onset
penetrance by age 50 is 93% in female mutation carriers and 68% in male mutation carriers
female mutation carriers have earlier age at onset compared to male mutation carriers
gestational choriocarcinoma is seen in female partners of lfs patients after parental-fetal transmission of germline tp53 mutation from male carriers


HPO:

31
li-fraumeni syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Lfs is typically considered to be a highly penetrant cancer syndrome with a 70% or higher lifetime risk of cancer in men and a 90% or higher lifetime risk of cancer in women [mai et al 2016, guha & malkin 2017]. another study reported an 80% risk of cancer by age 70, with 22% of the cancers occurring between ages 0 and15 years, 51% between ages 16 and 50 years, and 27% between ages 51 and 80 years [amadou et al 2018]....

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Cancer diseases
Anatomical: Neuronal diseases Endocrine diseases Bone diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare neurological diseases
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:3012
OMIM 56 151623
OMIM Phenotypic Series 56 PS151623
KEGG 36 H00881
MeSH 43 D016864
NCIt 49 C3476
SNOMED-CT 67 428850001
MESH via Orphanet 44 D016864
ICD10 via Orphanet 33 D48.9
UMLS via Orphanet 72 C0085390
Orphanet 58 ORPHA524
UMLS 71 C0085390 C1835398
Sources

Summaries for Li-Fraumeni Syndrome

About this section
OMIM : 56 Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. LFS is characterized by autosomal dominant inheritance and early onset of tumors, multiple tumors within an individual, and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS presents with a variety of tumor types. The most common types are soft tissue sarcomas and osteosarcomas, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Classic LFS is defined as a proband with a sarcoma before the age of 45 years and a first-degree relative with any cancer before the age of 45 years and 1 additional first- or second-degree relative in the same lineage with any cancer before the age of 45 years or a sarcoma at any age (Li et al., 1988). Li-Fraumeni-like syndrome (LFL) is defined as a proband with any childhood cancer, or a sarcoma, brain tumor, or adrenocortical tumor before the age of 45 years, plus a first- or second-degree relative in the same lineage with a typical LFS tumor at any age, and an additional first- or second-degree relative in the same lineage with any cancer before the age of 60 years (Birch et al., 1994). A less restrictive definition of LFL is 2 different LFS-related tumors in first- or second-degree relatives at any age (Eeles, 1995). Approximately 70% of LFS cases and 40% of LFL cases contain germline mutations in the p53 gene on chromosome 17p13.1 (Bachinski et al., 2005). (151623)

MalaCards based summary : Li-Fraumeni Syndrome, also known as sarcoma family syndrome of li and fraumeni, is related to li-fraumeni syndrome 1 and soft tissue sarcoma. An important gene associated with Li-Fraumeni Syndrome is TP53 (Tumor Protein P53), and among its related pathways/superpathways are MAPK signaling pathway and Cell cycle. The drugs Nicotinamide and tannic acid have been mentioned in the context of this disorder. Affiliated tissues include breast, brain and adrenal gland, and related phenotypes are lymphoma and osteosarcoma

Disease Ontology : 12 A syndrome characterized by autosomal dominant inheritance of increased risk of developing several types of cancer, including breast cancer, osteosarcomata and soft tissue sarcomata.

Genetics Home Reference : 25 Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults. The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome. A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.

NIH Rare Diseases : 52 Li-Fraumeni syndrome (LFS) is an inherited condition that is characterized by an increased risk for certain types of cancer . Affected people often develop cancer at an earlier age than expected and may be diagnosed with more than one cancer during their lifetime. LFS is primarily associated with sarcomas (cancers of muscle, bone or connective tissue ), breast cancer, brain tumors , leukemia and adrenocortical carcinoma ; however, many other types of cancer have been reported in people with this condition. It is caused by changes (mutations ) in the TP53 gene and is inherited in an autosomal dominant manner. Management may include high-risk cancer screening and/or prophylactic surgeries.

KEGG : 36 Li-Fraumeni syndrome (LFS) is a familial clustering of early onset tumors including sarcomas, breast cancers, brain tumors and adrenocortical carcinomas (ADR). Initially considered as a rare syndrome, LFS and its variants are increasingly recognized as one of the most frequent and diverse forms of predisposition to cancer. Most cases identified and characterized to date are associated with dominantly inherited germ line mutations in the tumor suppressor gene TP53 (p53). In a subset of non-p53 patients with LFS, CHEK2 has been identified as another predisposing locus. LFS is diagnosed on the basis of the confirmed clinical diagnostic criteria.

UniProtKB/Swiss-Prot : 73 Li-Fraumeni syndrome: An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.

Wikipedia : 74 Li-Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder that predisposes carriers to... more...

GeneReviews: NBK1311
Sources

Related Diseases for Li-Fraumeni Syndrome

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Diseases in the Li-Fraumeni Syndrome family:

Li-Fraumeni Syndrome 2 Li-Fraumeni Syndrome 1

Diseases related to Li-Fraumeni Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 484)
# Related Disease Score Top Affiliating Genes
1 li-fraumeni syndrome 1 35.6 WRAP53 TP53 CHEK2
2 soft tissue sarcoma 34.0 TP53 MDM2 EGFR
3 gastric cancer 33.6 TP53 RB1 PTEN MLH1 EGFR CHEK2
4 juvenile pilocytic astrocytoma 33.3 PTEN NF1 IDH1
5 glioblastoma multiforme 33.3 TP53 RB1 PTEN NF1 MDM2 IDH1
6 medulloblastoma 33.2 TP53 RB1 PTEN NF1 MDM2 IDH1
7 osteogenic sarcoma 32.3 TP53 RB1 MDM2 CHEK2 CDKN2A CDKN1A
8 rhabdomyosarcoma 32.0 TP53 RB1 PTEN MDM2 EGFR CDKN2A
9 liposarcoma 32.0 TP53 RB1 PTEN MDM2 CDKN2A
10 leiomyosarcoma 32.0 TP53 RB1 NF1 MDM2 CDKN2A
11 bilateral breast cancer 31.8 PTEN MLH1 CHEK2 CDKN2A BRCA2 BRCA1
12 leukemia 31.7 TP53 RB1 NF1 CHEK2 CDKN2A ATM
13 brain cancer 31.6 TP53 RB1 PTEN NF1 MDM2 IDH1
14 papilloma 31.6 TP53 RB1 PTEN EGFR CHEK2 CDKN2A
15 in situ carcinoma 31.6 TP53 PTEN EGFR CDKN2A BRCA2 BRCA1
16 adenocarcinoma 31.6 TP53 RB1 PTEN MLH1 MDM2 EGFR
17 myelodysplastic syndrome 31.5 TP53 PTEN NF1 MDM2 IDH1 CHEK2
18 b-cell lymphoma 31.5 TP53 RB1 MDM2 CDKN2A CDKN1A ATM
19 benign ependymoma 31.5 NF1 MDM2 EGFR
20 ductal carcinoma in situ 31.4 TP53 PTEN EGFR CDKN2A BRCA2 BRCA1
21 squamous cell papilloma 31.4 TP53 CDKN2A
22 lung cancer susceptibility 3 31.4 TP53 RB1 PTEN NF1 MDM2 IDH1
23 meningioma, familial 31.4 TP53 PTEN NF1 IDH1 EGFR CDKN2A
24 lymphoma 31.4 TP53 RB1 MDM2 EGFR CHEK2 CDKN2A
25 wilms tumor predisposition 31.3 TP53 NF1 BRCA2
26 ataxia-telangiectasia 31.3 TP53 MDM2 CHEK2 CHEK1 CDKN1A BRCA2
27 fallopian tube carcinoma 31.3 TP53 PTEN BRCA2 BRCA1
28 suppressor of tumorigenicity 3 31.3 TP53 RB1 CDKN2A CDKN1A
29 malignant peritoneal mesothelioma 31.3 EGFR CDKN2A
30 leukemia, chronic myeloid 31.3 TP53 PTEN NF1 EGFR CDKN1A
31 skin carcinoma 31.3 XPC TP53 EGFR CDKN2A
32 well-differentiated liposarcoma 31.3 TP53 MDM2 CDKN2A
33 lung benign neoplasm 31.3 TP53 RB1 EGFR CDKN2A
34 small cell carcinoma 31.3 TP53 PTEN EGFR CHEK2 CDKN2A
35 rectum adenocarcinoma 31.3 TP53 MLH1 EGFR
36 laryngeal squamous cell carcinoma 31.3 TP53 PTEN EGFR CDKN2A
37 xeroderma pigmentosum, variant type 31.2 XPC TP53 MLH1 CHEK2 CHEK1 BRCA2
38 female breast cancer 31.2 TP53 EGFR BRCA2 BRCA1 ATM
39 melanoma 31.2 TP53 RB1 PTEN MDM2 IDH1 EGFR
40 spitz nevus 31.2 TP53 CDKN2A
41 myxofibrosarcoma 31.2 TP53 MDM2 CDKN1A
42 familial retinoblastoma 31.2 TP53 RB1 NF1 MDM2 CDKN2A
43 oral cancer 31.2 TP53 EGFR CDKN2A
44 lynch syndrome 31.2 TP53 PTEN NF1 MLH1 MDM2 EGFR
45 hereditary breast ovarian cancer syndrome 31.2 TP53 PTEN NF1 MLH1 CHEK2 CDKN2A
46 bone cancer 31.2 TP53 RB1 IDH1 EGFR CDKN2A
47 kidney cancer 31.2 TP53 PTEN EGFR CDKN2A CDKN1A
48 basal cell carcinoma 31.2 TP53 PTEN EGFR CHEK2 CDKN2A CDKN1A
49 colon adenocarcinoma 31.1 TP53 PTEN MLH1 EGFR CDKN1A CAV1
50 skin melanoma 31.1 TP53 PTEN MLH1 MDM2 CDKN2A CDKN1A

Graphical network of the top 20 diseases related to Li-Fraumeni Syndrome:



Diseases related to Li-Fraumeni Syndrome
Sources

Symptoms & Phenotypes for Li-Fraumeni Syndrome

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Human phenotypes related to Li-Fraumeni Syndrome:

58 31 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 lymphoma 58 31 hallmark (90%) Occasional (29-5%) HP:0002665
2 osteosarcoma 58 31 hallmark (90%) Occasional (29-5%) HP:0002669
3 breast carcinoma 58 31 hallmark (90%) Frequent (79-30%) HP:0003002
4 neoplasm of the pancreas 58 31 hallmark (90%) Very rare (<4-1%) HP:0002894
5 neoplasm of the skin 31 hallmark (90%) HP:0008069
6 neoplasm of the colon 31 hallmark (90%) HP:0100273
7 neoplasm of the nervous system 31 hallmark (90%) HP:0004375
8 neoplasm of the adrenal cortex 31 hallmark (90%) HP:0100641
9 progressive encephalopathy 31 hallmark (90%) HP:0002448
10 melanoma 58 31 occasional (7.5%) Very rare (<4-1%) HP:0002861
11 colon cancer 58 31 Very rare (<4-1%) HP:0003003
12 adrenocortical carcinoma 58 31 Occasional (29-5%) HP:0006744
13 prostate cancer 58 31 Very rare (<4-1%) HP:0012125
14 choriocarcinoma 58 31 Very rare (<4-1%) HP:0100768
15 neoplasm of the lung 58 Very rare (<4-1%)
16 myelodysplasia 58 Very rare (<4-1%)
17 neoplasm 58 Very frequent (99-80%)
18 neoplasm of the central nervous system 58 Occasional (29-5%)
19 leukemia 58 Occasional (29-5%)
20 rhabdomyosarcoma 58 Occasional (29-5%)
21 acute leukemia 31 HP:0002488
22 astrocytoma 58 Occasional (29-5%)
23 neoplasm of the gastrointestinal tract 58 Occasional (29-5%)
24 stomach cancer 58 Occasional (29-5%)
25 neoplasm of the rectum 58 Very rare (<4-1%)
26 colorectal polyposis 58 Occasional (29-5%)
27 nephroblastoma 31 HP:0002667
28 ovarian neoplasm 58 Very rare (<4-1%)
29 acute lymphoblastic leukemia 58 Very rare (<4-1%)
30 renal neoplasm 58 Very rare (<4-1%)
31 thyroid carcinoma 58 Very rare (<4-1%)
32 testicular neoplasm 58 Very rare (<4-1%)
33 lung adenocarcinoma 31 HP:0030078
34 medulloblastoma 58 Very rare (<4-1%)
35 acute myeloid leukemia 58 Very rare (<4-1%)
36 hodgkin lymphoma 58 Very rare (<4-1%)
37 non-hodgkin lymphoma 58 Very rare (<4-1%)
38 neoplasm of head and neck 58 Very rare (<4-1%)
39 neoplasm of the larynx 58 Very rare (<4-1%)
40 soft tissue sarcoma 31 HP:0030448
41 ependymoma 58 Occasional (29-5%)
42 glioblastoma multiforme 58 Occasional (29-5%)
43 central primitive neuroectodermal tumor 58 Occasional (29-5%)
44 choroid plexus carcinoma 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

56
Neoplasia:
colon cancer
lung adenocarcinoma
prostate cancer
wilms tumor
breast cancer
more

Clinical features from OMIM:

151623

GenomeRNAi Phenotypes related to Li-Fraumeni Syndrome according to GeneCards Suite gene sharing:

26 (show top 50) (show all 64)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.77 EGFR
2 Decreased viability GR00055-A-2 10.77 EGFR
3 Decreased viability GR00221-A-1 10.77 CDKN2A CHEK1 EGFR NF1
4 Decreased viability GR00221-A-2 10.77 BRCA1 CHEK1 CHEK2 NF1
5 Decreased viability GR00221-A-3 10.77 ATM BRCA1 CDKN2A CHEK1 CHEK2
6 Decreased viability GR00221-A-4 10.77 ATM CDKN2A CHEK1 CHEK2 EGFR NF1
7 Decreased viability GR00240-S-1 10.77 CHEK1
8 Decreased viability GR00249-S 10.77 CHEK1 NF1
9 Decreased viability GR00301-A 10.77 BRCA1 CHEK1
10 Decreased viability GR00342-S-2 10.77 CHEK2
11 Decreased viability GR00381-A-1 10.77 CHEK1
12 Decreased viability GR00386-A-1 10.77 CHEK1 NF1
13 Decreased viability GR00402-S-2 10.77 CHEK1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-1 10.64 MLH1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.64 ATM
16 Increased shRNA abundance (Z-score > 2) GR00366-A-108 10.64 CDKN1A
17 Increased shRNA abundance (Z-score > 2) GR00366-A-11 10.64 ATM
18 Increased shRNA abundance (Z-score > 2) GR00366-A-114 10.64 ATM
19 Increased shRNA abundance (Z-score > 2) GR00366-A-121 10.64 CHEK1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-122 10.64 ATM CHEK1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-124 10.64 MLH1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-13 10.64 CHEK1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-137 10.64 BRCA1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-139 10.64 ATM BRCA1 CDKN1A CHEK1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-142 10.64 CDKN1A
26 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.64 CHEK1
27 Increased shRNA abundance (Z-score > 2) GR00366-A-148 10.64 CHEK1
28 Increased shRNA abundance (Z-score > 2) GR00366-A-149 10.64 ATM
29 Increased shRNA abundance (Z-score > 2) GR00366-A-151 10.64 ATM
30 Increased shRNA abundance (Z-score > 2) GR00366-A-159 10.64 ATM
31 Increased shRNA abundance (Z-score > 2) GR00366-A-160 10.64 ATM
32 Increased shRNA abundance (Z-score > 2) GR00366-A-168 10.64 BRCA1
33 Increased shRNA abundance (Z-score > 2) GR00366-A-172 10.64 RB1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.64 RB1
35 Increased shRNA abundance (Z-score > 2) GR00366-A-179 10.64 CHEK1
36 Increased shRNA abundance (Z-score > 2) GR00366-A-181 10.64 RB1
37 Increased shRNA abundance (Z-score > 2) GR00366-A-195 10.64 CHEK1 MLH1
38 Increased shRNA abundance (Z-score > 2) GR00366-A-200 10.64 MLH1
39 Increased shRNA abundance (Z-score > 2) GR00366-A-204 10.64 BRCA1
40 Increased shRNA abundance (Z-score > 2) GR00366-A-210 10.64 RB1
41 Increased shRNA abundance (Z-score > 2) GR00366-A-211 10.64 BRCA1
42 Increased shRNA abundance (Z-score > 2) GR00366-A-26 10.64 CHEK1
43 Increased shRNA abundance (Z-score > 2) GR00366-A-38 10.64 CDKN1A
44 Increased shRNA abundance (Z-score > 2) GR00366-A-39 10.64 CDKN1A
45 Increased shRNA abundance (Z-score > 2) GR00366-A-41 10.64 ATM
46 Increased shRNA abundance (Z-score > 2) GR00366-A-43 10.64 RB1
47 Increased shRNA abundance (Z-score > 2) GR00366-A-50 10.64 RB1
48 Increased shRNA abundance (Z-score > 2) GR00366-A-60 10.64 CHEK1
49 Increased shRNA abundance (Z-score > 2) GR00366-A-63 10.64 CHEK1
50 Increased shRNA abundance (Z-score > 2) GR00366-A-65 10.64 ATM

MGI Mouse Phenotypes related to Li-Fraumeni Syndrome:

45 (show all 24)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.5 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
2 homeostasis/metabolism MP:0005376 10.5 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
3 hematopoietic system MP:0005397 10.46 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
4 endocrine/exocrine gland MP:0005379 10.45 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
5 mortality/aging MP:0010768 10.43 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
6 behavior/neurological MP:0005386 10.42 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
7 growth/size/body region MP:0005378 10.41 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
8 immune system MP:0005387 10.41 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
9 embryo MP:0005380 10.4 ATM BRCA1 BRCA2 CDKN1A CDKN2A CHEK1
10 integument MP:0010771 10.4 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
11 cardiovascular system MP:0005385 10.38 ATM BRCA1 CAV1 CDKN1A CDKN2A CHEK1
12 digestive/alimentary MP:0005381 10.37 BRCA1 BRCA2 CAV1 CDKN1A CDKN2A EGFR
13 neoplasm MP:0002006 10.34 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
14 nervous system MP:0003631 10.28 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
15 adipose tissue MP:0005375 10.22 ATM BRCA1 CAV1 CDKN1A EGFR PTEN
16 limbs/digits/tail MP:0005371 10.16 BRCA1 BRCA2 CDKN1A EGFR MDM2 NF1
17 muscle MP:0005369 10.16 BRCA1 CAV1 CDKN1A CDKN2A EGFR MDM2
18 liver/biliary system MP:0005370 10.15 CAV1 CDKN1A CDKN2A EGFR MDM2 NF1
19 reproductive system MP:0005389 10.13 ATM BRCA1 BRCA2 CAV1 CDKN1A CDKN2A
20 pigmentation MP:0001186 10.02 BRCA1 CDKN2A CHEK1 EGFR MDM2 NF1
21 renal/urinary system MP:0005367 9.97 BRCA1 CAV1 CDKN1A EGFR MDM2 NF1
22 respiratory system MP:0005388 9.9 BRCA1 CAV1 CDKN1A CDKN2A EGFR IDH1
23 skeleton MP:0005390 9.73 BRCA1 BRCA2 CAV1 CDKN1A CDKN2A EGFR
24 vision/eye MP:0005391 9.28 CDKN1A CDKN2A EGFR MLH1 NF1 PTEN
Sources

Drugs & Therapeutics for Li-Fraumeni Syndrome

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Drugs for Li-Fraumeni Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 16)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nicotinamide Approved, Investigational Phase 1, Phase 2 98-92-0 936
2
tannic acid Approved Phase 1, Phase 2 1401-55-4
3
Benzocaine Approved, Investigational Phase 1, Phase 2 94-09-7, 1994-09-7 2337
4
Cetuximab Approved Phase 2 205923-56-4 56842117 2333
5
Niacin Approved, Investigational, Nutraceutical Phase 1, Phase 2 59-67-6 938
6 Vitamins Phase 1, Phase 2
7 Vitamin B Complex Phase 1, Phase 2
8 Vitamin B3 Phase 1, Phase 2
9 Nicotinic Acids Phase 1, Phase 2
10 Antineoplastic Agents, Immunological Phase 2
11
Phosphocreatine Nutraceutical Phase 1, Phase 2 67-07-2 587
12
Metformin Approved Phase 1 657-24-9 14219 4091
13 Hypoglycemic Agents Phase 1
14 Anesthetics
15 Chelating Agents Early Phase 1
16 Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate Early Phase 1

Interventional clinical trials:

(show all 18)
# Name Status NCT ID Phase Drugs
1 LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome) Unknown status NCT01464086 Phase 3
2 Exploratory Study of Nicotinamide Riboside on Mitochondrial Function in Li-Fraumeni Syndrome Completed NCT03789175 Phase 1, Phase 2
3 Phase II Trial of Cetuximab in Patients With Metastatic and/or Locally Advanced Soft Tissue and Bony Sarcomas Completed NCT00148109 Phase 2 Cetuximab;Cetuximab
4 A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome Completed NCT01981525 Phase 1 Metformin
5 Magnetic Resonance Imaging Screening In Li Fraumeni Syndrome: An Exploratory Whole Body MRI Study Completed NCT01737255
6 Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting Completed NCT02289326
7 Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer Completed NCT00040222
8 Screening With Whole Body MRI For Detection Of Primary Tumors In Children And Adults With Li-Fraumeni Syndrome (LFS) And Other Cancer Predisposition Syndromes Recruiting NCT02950987
9 Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders Recruiting NCT04367246
10 Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome Recruiting NCT01443468
11 Cardiovascular Disease Discovery Protocol Recruiting NCT01143454
12 International Pediatric Adrenocortical Tumor Registry Recruiting NCT00700414
13 Natural History and Biospecimen Acquisition Study for Children and Adults With Rare Solid Tumors Recruiting NCT03739827
14 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
15 Novel Approaches to Molecular and Clinical Surveillance in Li-Fraumeni Syndrome - Pilot Study. Enrolling by invitation NCT03176836
16 Metabolic Regulation by Tumor Suppressor p53 in Li-Fraumeni Syndrome Enrolling by invitation NCT00406445
17 AYA-RISE: Refining a Scalable, Patient- and Family-centered Intervention to Improve Cancer Risk Communication and Decision-making Among Adolescents and Young Adults With Cancer Risk Syndromes Not yet recruiting NCT04323774
18 Abbreviated MRI Protocol: Initial Experience With Dotarem® (Gadoterate Meglumine) Not yet recruiting NCT04341129 Early Phase 1 Abbreviated MRI protocol: initial experience with Dotarem® (Gadoterate Meglumine)

Search NIH Clinical Center for Li-Fraumeni Syndrome

Cochrane evidence based reviews: li-fraumeni syndrome

Sources

Genetic Tests for Li-Fraumeni Syndrome

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Genetic tests related to Li-Fraumeni Syndrome:

# Genetic test Affiliating Genes
1 Li-Fraumeni Syndrome 29
Sources

Anatomical Context for Li-Fraumeni Syndrome

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MalaCards organs/tissues related to Li-Fraumeni Syndrome:

40
Breast, Brain, Adrenal Gland, Bone, Testes, Lung, Kidney
Sources

Publications for Li-Fraumeni Syndrome

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Articles related to Li-Fraumeni Syndrome:

(show top 50) (show all 1098)
# Title Authors PMID Year
1
Germline TP53 mutations and Li-Fraumeni syndrome. 61 6 56 54
12619118 2003
2
Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family. 54 61 6 56
10484981 1999
3
Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation. 6 56 61
15977174 2005
4
Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. 6 56 61
8118819 1994
5
Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. 61 6 56
1978757 1990
6
Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. 61 24 56
27501770 2016
7
Germline mutations in the TP53 gene. 56 6
8718514 1995
8
High frequency of de novo mutations in Li-Fraumeni syndrome. 56 54 61
19556618 2009
9
Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin. 54 61 56
15381368 2004
10
Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. 61 54 6
11719428 2001
11
p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. 6 61 54
11479205 2001
12
Mechanism of functional inactivation of a Li-Fraumeni syndrome p53 that has a mutation outside of the DNA-binding domain. 54 61 6
11245491 2001
13
Exclusion of the genes CDKN2 and PTEN as causative gene defects in Li-Fraumeni syndrome. 54 56 61
10389970 1999
14
Two Li-Fraumeni syndrome families with novel germline p53 mutations: loss of the wild-type p53 allele in only 50% of tumours. 54 61 6
9569035 1998
15
Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. 6 54 61
1644930 1992
16
Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein. 61 54 6
1631137 1992
17
A germ line mutation in exon 5 of the p53 gene in an extended cancer family. 54 6 61
1933902 1991
18
p53 germline mutations in Li-Fraumeni syndrome. 61 54 6
1683921 1991
19
Increased oxidative metabolism in the Li-Fraumeni syndrome. 61 56
23484829 2013
20
Gastric cancer in individuals with Li-Fraumeni syndrome. 61 56
21552135 2011
21
Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. 56 61
18685109 2008
22
Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23. 56 61
15695383 2005
23
A novel genetic modifier of p53, mop1, results in embryonic lethality. 56 61
15181534 2004
24
Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. 61 56
14583457 2003
25
A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. 6 61
12094328 2002
26
Individual-specific liability groups in genetic linkage, with applications to kindreds with Li-Fraumeni syndrome. 61 56
11822026 2002
27
Relative frequency and morphology of cancers in carriers of germline TP53 mutations. 56 61
11498785 2001
28
Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. 6 61
10797439 2000
29
Predominance of brain tumors in an extended Li-Fraumeni (SBLA) kindred, including a case of Sturge-Weber syndrome. 56 61
10640978 2000
30
Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. 61 6
10617473 1999
31
Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors. 6 61
10486318 1999
32
Li-Fraumeni Syndrome 6 61
20301488 1999
33
Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family. 61 56
9703430 1998
34
Multiple primary cancers in families with Li-Fraumeni syndrome. 61 56
9554443 1998
35
Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. 61 56
9242456 1997
36
Tumors associated with p53 germline mutations: a synopsis of 91 families. 56 61
9006316 1997
37
Li-Fraumeni syndrome--a molecular and clinical review. 56 61
9218725 1997
38
Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. 56 61
7887414 1995
39
Two germ-line mutations affecting the same nucleotide at codon 257 of p53 gene, a rare site for mutations. 6 61
8134127 1994
40
Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. 6 61
1565143 1992
41
Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. 61 6
1565144 1992
42
Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. 61 6
2259385 1990
43
Genotype-phenotype associations among panel-based TP53+ subjects. 24 61
31105275 2019
44
Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study). 24 61
31041842 2019
45
Clinical spectrum of Li-Fraumeni syndrome/Li-Fraumeni-like syndrome in Brazilian individuals with the TP53 p.R337H mutation. 24 61
30974190 2019
46
Hematologic malignancies and Li-Fraumeni syndrome. 24 61
30709875 2019
47
Variable population prevalence estimates of germline TP53 variants: A gnomAD-based analysis. 61 24
30352134 2019
48
Earlier Colorectal Cancer Screening May Be Necessary In Patients With Li-Fraumeni Syndrome. 61 24
30243621 2019
49
Contribution of genotoxic anticancer treatments to the development of multiple primary tumours in the context of germline TP53 mutations. 24 61
30072235 2018
50
Somatic TP53 variants frequently confound germ-line testing results. 61 24
29189820 2018
Sources

Variations for Li-Fraumeni Syndrome

About this section

ClinVar genetic disease variations for Li-Fraumeni Syndrome:

6 (show top 50) (show all 1036) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TP53 NM_001126112.2(TP53):c.574C>T (p.Gln192Ter)SNV Pathogenic 406579 rs866380588 17:7578275-7578275 17:7674957-7674957
2 TP53 NM_001126112.2(TP53):c.537T>A (p.His179Gln)SNV Pathogenic 406578 rs876660821 17:7578393-7578393 17:7675075-7675075
3 TP53 NM_001126112.2(TP53):c.716del (p.Asn239fs)deletion Pathogenic 406580 rs1060501197 17:7577565-7577565 17:7674247-7674247
4 TP53 NM_001126112.2(TP53):c.321C>A (p.Tyr107Ter)SNV Pathogenic 406599 rs770776262 17:7579366-7579366 17:7676048-7676048
5 TP53 NM_001126112.2(TP53):c.448_460del (p.Thr150fs)deletion Pathogenic 406602 rs1064792930 17:7578470-7578482 17:7675152-7675164
6 TP53 NM_001126112.2(TP53):c.790del (p.Leu264fs)deletion Pathogenic 406573 rs1060501194 17:7577148-7577148 17:7673830-7673830
7 TP53 NM_001126112.2(TP53):c.1024del (p.Arg342fs)deletion Pathogenic 428885 rs1131691022 17:7574003-7574003 17:7670685-7670685
8 TP53 NM_001126112.2(TP53):c.993+1deldeletion Pathogenic 428898 rs1131691033 17:7576852-7576852 17:7673534-7673534
9 TP53 NM_001126112.2(TP53):c.323_329dup (p.Leu111fs)duplication Pathogenic 428860 rs1131691004 17:7579357-7579358 17:7676039-7676040
10 TP53 NM_001126112.2(TP53):c.334_364dup (p.Val122fs)duplication Pathogenic 430665 rs1555526495 17:7579322-7579323 17:7676004-7676005
11 TP53 NM_000546.5(TP53):c.2588dupduplication Pathogenic 437018 rs1555523630 17:7571520-7571521 17:7668202-7668203
12 TP53 NM_001126112.2(TP53):c.438G>A (p.Trp146Ter)SNV Pathogenic 428890 rs1131691026 17:7578492-7578492 17:7675174-7675174
13 TP53 NM_001126112.2(TP53):c.1015G>T (p.Glu339Ter)SNV Pathogenic 438708 rs17882252 17:7574012-7574012 17:7670694-7670694
14 TP53 NM_001126112.2(TP53):c.990_993del (p.Gln331fs)deletion Pathogenic 458579 rs1555524949 17:7576853-7576856 17:7673535-7673538
15 TP53 NM_001126112.2(TP53):c.870dup (p.Lys291fs)duplication Pathogenic 458573 rs1555525140 17:7577067-7577068 17:7673749-7673750
16 TP53 NM_001126112.2(TP53):c.112del (p.Gln38fs)deletion Pathogenic 458519 rs1555526795 17:7579575-7579575 17:7676257-7676257
17 TP53 NM_001126112.2(TP53):c.783-1G>ASNV Pathogenic 458565 rs1555525367 17:7577156-7577156 17:7673838-7673838
18 TP53 NM_001126112.2(TP53):c.715_724del (p.Asn239fs)deletion Pathogenic 458558 rs1555525518 17:7577557-7577566 17:7674239-7674248
19 TP53 NM_001126112.2(TP53):c.156dup (p.Trp53fs)duplication Pathogenic 458525 rs1555526748 17:7579530-7579531 17:7676212-7676213
20 TP53 NM_001126112.2(TP53):c.673-2A>GSNV Pathogenic 458555 rs1555525585 17:7577610-7577610 17:7674292-7674292
21 TP53 NM_001126112.2(TP53):c.372C>A (p.Cys124Ter)SNV Pathogenic 458537 rs1555526478 17:7579315-7579315 17:7675997-7675997
22 TP53 NM_001126112.2(TP53):c.848_857del (p.Arg283fs)deletion Pathogenic 458569 rs1555525170 17:7577081-7577090 17:7673763-7673772
23 TP53 NM_001126112.2(TP53):c.831T>A (p.Cys277Ter)SNV Pathogenic 492746 rs1057523347 17:7577107-7577107 17:7673789-7673789
24 TP53 NC_000017.11:g.(?_7669603)_(7676600_?)deldeletion Pathogenic 528283 17:7572921-7579918 17:7669603-7676600
25 TP53 NM_001126112.2(TP53):c.522_559+5deldeletion Pathogenic 528272 rs1555525957 17:7578366-7578408 17:7675048-7675090
26 TP53 NM_001126112.2(TP53):c.473G>T (p.Arg158Leu)SNV Pathogenic 528248 rs587782144 17:7578457-7578457 17:7675139-7675139
27 TP53 NM_001126112.2(TP53):c.295del (p.Ser99fs)deletion Pathogenic 528244 rs1555526593 17:7579392-7579392 17:7676074-7676074
28 TP53 NM_001126112.2(TP53):c.155_156del (p.Gln52fs)deletion Pathogenic 528265 rs1555526750 17:7579531-7579532 17:7676213-7676214
29 TP53 NM_001126112.2(TP53):c.844_847delinsAG (p.Arg283fs)indel Pathogenic 528267 rs1555525209 17:7577091-7577094 17:7673773-7673776
30 TP53 NM_001126112.2(TP53):c.45del (p.Gln16fs)deletion Pathogenic 528242 rs1555526997 17:7579868-7579868 17:7676550-7676550
31 TP53 NM_001126112.2(TP53):c.86del (p.Asn29fs)deletion Pathogenic 528243 rs1555526931 17:7579710-7579710 17:7676392-7676392
32 TP53 NM_001126112.2(TP53):c.993+1G>ASNV Pathogenic 528261 rs11575997 17:7576852-7576852 17:7673534-7673534
33 TP53 NM_001126112.2(TP53):c.917_919+10deldeletion Pathogenic 528253 rs1555525040 17:7577009-7577021 17:7673691-7673703
34 TP53 NC_000017.11:g.(?_7669599)_(7676604_?)deldeletion Pathogenic 583792 17:7572917-7579922 17:7669599-7676604
35 TP53 NM_001126112.2(TP53):c.517_535dup (p.His179fs)duplication Pathogenic 580994 rs1567552753 17:7578394-7578395 17:7675076-7675077
36 TP53 NM_001126112.2(TP53):c.818_819GT[1] (p.Val274fs)short repeat Pathogenic 575419 rs1567547933 17:7577117-7577118 17:7673799-7673800
37 TP53 NM_001126112.2(TP53):c.501del (p.Gln167fs)deletion Pathogenic 566517 rs1567553148 17:7578429-7578429 17:7675111-7675111
38 TP53 NM_001126112.2(TP53):c.492_493delinsCT (p.Lys164_Gln165delinsAsnTer)indel Pathogenic 579699 rs1567553215 17:7578437-7578438 17:7675119-7675120
39 TP53 NM_001126112.2(TP53):c.151G>T (p.Glu51Ter)SNV Pathogenic 568781 rs1567556930 17:7579536-7579536 17:7676218-7676218
40 TP53 NM_001126112.2(TP53):c.917_919+6deldeletion Pathogenic 570307 rs1567546716 17:7577013-7577021 17:7673695-7673703
41 TP53 NM_001126112.2(TP53):c.837_838GA[2] (p.Asp281fs)short repeat Pathogenic 570804 rs1567547661 17:7577096-7577097 17:7673778-7673779
42 TP53 NM_001126112.2(TP53):c.310C>T (p.Gln104Ter)SNV Pathogenic 566924 rs1567555934 17:7579377-7579377 17:7676059-7676059
43 TP53 NM_001126112.2(TP53):c.140del (p.Pro47fs)deletion Pathogenic 574668 rs1567557016 17:7579547-7579547 17:7676229-7676229
44 TP53 NM_001126112.2(TP53):c.1043_1051delinsG (p.Leu348_Lys351delinsTer)indel Pathogenic 576681 rs1567541951 17:7573976-7573984 17:7670658-7670666
45 TP53 NM_001126112.2(TP53):c.949del (p.Gln317fs)deletion Pathogenic 577286 rs1567546196 17:7576897-7576897 17:7673579-7673579
46 TP53 NM_001126112.2(TP53):c.702_714del (p.His233_Tyr234insTer)deletion Pathogenic 574669 rs1567549676 17:7577567-7577579 17:7674249-7674261
47 TP53 NM_001126112.2(TP53):c.817C>G (p.Arg273Gly)SNV Pathogenic 634682 rs121913343 17:7577121-7577121 17:7673803-7673803
48 TP53 NM_001126112.2(TP53):c.661G>T (p.Glu221Ter)SNV Pathogenic 634754 rs786201592 17:7578188-7578188 17:7674870-7674870
49 TP53 NM_001126112.2(TP53):c.511G>T (p.Glu171Ter)SNV Pathogenic 634771 rs587781845 17:7578419-7578419 17:7675101-7675101
50 TP53 NM_001126112.2(TP53):c.437G>A (p.Trp146Ter)SNV Pathogenic 634785 rs1206165503 17:7578493-7578493 17:7675175-7675175

UniProtKB/Swiss-Prot genetic disease variations for Li-Fraumeni Syndrome:

73 (show top 50) (show all 83)
# Symbol AA change Variation ID SNP ID
1 TP53 p.Met133Thr VAR_005875 rs28934873
2 TP53 p.Ala138Pro VAR_005881 rs28934875
3 TP53 p.Cys141Tyr VAR_005886 rs587781288
4 TP53 p.Pro151Ser VAR_005895 rs28934874
5 TP53 p.Pro151Thr VAR_005896 rs28934874
6 TP53 p.Pro152Leu VAR_005897 rs587782705
7 TP53 p.Arg158Gly VAR_005906
8 TP53 p.Arg158His VAR_005907 rs587782144
9 TP53 p.Val173Met VAR_005926 rs876660754
10 TP53 p.Arg175Gly VAR_005929 rs138729528
11 TP53 p.Arg175Leu VAR_005930 rs28934578
12 TP53 p.Arg175His VAR_005932 rs28934578
13 TP53 p.His193Arg VAR_005948 rs786201838
14 TP53 p.Arg213Gln VAR_005955 rs587778720
15 TP53 p.Tyr220Cys VAR_005957 rs121912666
16 TP53 p.Tyr234Cys VAR_005963 rs587780073
17 TP53 p.Met237Ile VAR_005965 rs587782664
18 TP53 p.Ser241Phe VAR_005969 rs28934573
19 TP53 p.Gly245Cys VAR_005972 rs28934575
20 TP53 p.Gly245Asp VAR_005973 rs121912656
21 TP53 p.Gly245Ser VAR_005974 rs28934575
22 TP53 p.Gly245Val VAR_005975 rs121912656
23 TP53 p.Met246Val VAR_005978 rs483352695
24 TP53 p.Arg248Gln VAR_005983 rs11540652
25 TP53 p.Arg248Trp VAR_005984 rs121912651
26 TP53 p.Leu252Pro VAR_005988 rs121912653
27 TP53 p.Glu258Lys VAR_005991 rs121912652
28 TP53 p.Val272Leu VAR_005992 rs121912657
29 TP53 p.Arg273Cys VAR_005993 rs121913343
30 TP53 p.Arg273Gly VAR_005994
31 TP53 p.Arg273His VAR_005995 rs28934576
32 TP53 p.Cys275Tyr VAR_005998 rs863224451
33 TP53 p.Pro278Leu VAR_006003 rs876659802
34 TP53 p.Pro278Ser VAR_006004 rs17849781
35 TP53 p.Pro278Thr VAR_006005 rs17849781
36 TP53 p.Arg282Trp VAR_006016 rs28934574
37 TP53 p.Arg283Cys VAR_006017 rs149633775
38 TP53 p.Glu285Gln VAR_006024
39 TP53 p.Glu286Ala VAR_006026 rs105751998
40 TP53 p.Pro309Ser VAR_006038 rs155552501
41 TP53 p.Gly325Val VAR_006039 rs121912659
42 TP53 p.Arg337Cys VAR_006041 rs587782529
43 TP53 p.Lys292Ile VAR_015819 rs121912663
44 TP53 p.Tyr163Cys VAR_033035 rs148924904
45 TP53 p.Arg337His VAR_035016 rs121912664
46 TP53 p.Arg213Pro VAR_036506 rs587778720
47 TP53 p.Arg273Leu VAR_036509 rs28934576
48 TP53 p.Pro82Leu VAR_044621 rs534447939
49 TP53 p.Gly105Cys VAR_044661
50 TP53 p.Lys132Glu VAR_044740 rs747342068

Cosmic variations for Li-Fraumeni Syndrome:

9 (show top 50) (show all 626)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)		 Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM87906219 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.728T>C p.M243T 17:7674235-7674235 12
2 COSM88149182 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.668C>G p.P223R 17:7674863-7674863 12
3 COSM87949760 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.871A>C p.K291Q 17:7673749-7673749 12
4 COSM87912949 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.394A>G p.K132E 17:7675218-7675218 12
5 COSM88120884 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.739A>G p.N247D 17:7674224-7674224 12
6 COSM87911460 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.961A>T p.K321* 17:7673567-7673567 12
7 COSM87900604 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.637C>T p.R213* 17:7674894-7674894 12
8 COSM87897711 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.818G>A p.R273H 17:7673802-7673802 12
9 COSM87898463 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.733G>T p.G245C 17:7674230-7674230 12
10 COSM88205650 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.611A>G p.E204G 17:7674920-7674920 12
11 COSM87898578 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.733G>A p.G245S 17:7674230-7674230 12
12 COSM87897745 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.524G>A p.R175H 17:7675088-7675088 12
13 COSM87897839 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.701A>G p.Y234C 17:7674262-7674262 12
14 COSM87898351 TP53 soft tissue,striated muscle,rhabdomyosarcoma,NS c.743G>A p.R248Q 17:7674220-7674220 12
15 COSM88094731 SOX9 soft tissue,striated muscle,rhabdomyosarcoma,NS c.76A>G p.M26V 17:72121467-72121467 12
16 COSM84133785 RICTOR soft tissue,striated muscle,rhabdomyosarcoma,NS c.2898-1G>T p.? 5:38952426-38952426 12
17 COSM97041246 PTPRT soft tissue,striated muscle,rhabdomyosarcoma,NS c.2277G>T p.Q759H 20:42248779-42248779 12
18 COSM146438832 PTPN11 soft tissue,striated muscle,rhabdomyosarcoma,NS c.214G>A p.A72T 12:112450394-112450394 12
19 COSM146438781 PTPN11 soft tissue,striated muscle,rhabdomyosarcoma,NS c.226G>C p.E76Q 12:112450406-112450406 12
20 COSM146439443 PTPN11 soft tissue,striated muscle,rhabdomyosarcoma,NS c.1520G>T p.G507V 12:112489084-112489084 12
21 COSM146438825 PTPN11 soft tissue,striated muscle,rhabdomyosarcoma,NS c.205G>A p.E69K 12:112450385-112450385 12
22 COSM90839845 PTCH1 soft tissue,striated muscle,rhabdomyosarcoma,NS c.208G>A p.A70T 9:95506593-95506593 12
23 COSM90587293 POLE soft tissue,striated muscle,rhabdomyosarcoma,NS c.5975G>C p.C1992S 12:132634215-132634215 12
24 COSM96437477 PIK3CG soft tissue,striated muscle,rhabdomyosarcoma,NS c.2638G>A p.E880K 7:106883041-106883041 12
25 COSM87132301 PIK3CA soft tissue,striated muscle,rhabdomyosarcoma,NS c.1624G>A p.E542K 3:179218294-179218294 12
26 COSM87132544 PIK3CA soft tissue,striated muscle,rhabdomyosarcoma,NS c.1636C>A p.Q546K 3:179218306-179218306 12
27 COSM87132245 PIK3CA soft tissue,striated muscle,rhabdomyosarcoma,NS c.3140A>G p.H1047R 3:179234297-179234297 12
28 COSM87138160 PIK3CA soft tissue,striated muscle,rhabdomyosarcoma,NS c.1625A>T p.E542V 3:179218295-179218295 12
29 COSM87225164 PIK3CA soft tissue,striated muscle,rhabdomyosarcoma,NS c.3023C>T p.S1008F 3:179234180-179234180 12
30 COSM87132308 PIK3CA soft tissue,striated muscle,rhabdomyosarcoma,NS c.1633G>A p.E545K 3:179218303-179218303 12
31 COSM88818803 PDGFRA soft tissue,striated muscle,rhabdomyosarcoma,NS c.3195G>C p.E1065D 4:54295197-54295197 12
32 COSM97687376 NTRK3 soft tissue,striated muscle,rhabdomyosarcoma,NS c.492C>A p.C164* 15:88137534-88137534 12
33 COSM97107326 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.181C>A p.Q61K 1:114713909-114713909 12
34 COSM97108079 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.183A>T p.Q61H 1:114713907-114713907 12
35 COSM97107379 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.35G>A p.G12D 1:114716126-114716126 12
36 COSM97107772 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.37G>C p.G13R 1:114716124-114716124 12
37 COSM97107813 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.34G>A p.G12S 1:114716127-114716127 12
38 COSM97107359 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.182A>G p.Q61R 1:114713908-114713908 12
39 COSM97107717 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.38G>T p.G13V 1:114716123-114716123 12
40 COSM97107336 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.183A>C p.Q61H 1:114713907-114713907 12
41 COSM97107724 NRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.34G>T p.G12C 1:114716127-114716127 12
42 COSM88406309 NOTCH2 soft tissue,breast,sarcoma,NS c.1145A>G p.N382S 1:119968196-119968196 12
43 COSM87643288 NOTCH1 soft tissue,striated muscle,rhabdomyosarcoma,NS c.3277T>C p.Y1093H 9:136508280-136508280 12
44 COSM93680412 NF1 soft tissue,striated muscle,rhabdomyosarcoma,NS c.7870G>C p.A2624P 17:31357269-31357269 12
45 COSM84820183 MYOD1 soft tissue,striated muscle,rhabdomyosarcoma,NS c.365T>G p.L122R 11:17720147-17720147 12
46 COSM101727756 MAP3K1 soft tissue,striated muscle,rhabdomyosarcoma,NS c.1337G>A p.C446Y 5:56871945-56871945 12
47 COSM87804028 KRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.38G>A p.G13D 12:25245347-25245347 12
48 COSM87804075 KRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.34G>T p.G12C 12:25245351-25245351 12
49 COSM87804005 KRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.35G>A p.G12D 12:25245350-25245350 12
50 COSM87804083 KRAS soft tissue,striated muscle,rhabdomyosarcoma,NS c.35G>C p.G12A 12:25245350-25245350 12

Copy number variations for Li-Fraumeni Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 116393 17 6500000 10700000 Copy number TP53 Li-fraumeni syndrome
2 117991 17 7505821 7531588 Deletion TP53 Li-fraumeni syndrome
3 118109 17 7571720 7590863 Copy number TP53 Li-fraumeni syndrome
4 162983 22 23500000 25900000 Copy number Li-fraumeni syndrome
Sources

Expression for Li-Fraumeni Syndrome

About this section
Search GEO for disease gene expression data for Li-Fraumeni Syndrome.
Sources

Pathways for Li-Fraumeni Syndrome

About this section

Pathways related to Li-Fraumeni Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Cell cycle hsa04110
3 p53 signaling pathway hsa04115
4 Apoptosis hsa04210
5 Wnt signaling pathway hsa04310
6 Pathways in cancer hsa05200

Pathways related to Li-Fraumeni Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 85)
# Super pathways Score Top Affiliating Genes
1
ERK Signaling 63
Show member pathways
 13.94 TP53 RB1 PTEN NF1 MDM2 EGFR
2
Gene Expression 65
Show member pathways
 13.9 TP53 PTEN MLH1 MDM2 EGFR CHEK2
3
Cell Cycle, Mitotic 65
Show member pathways
 13.56 WRAP53 TP53 RB1 MLH1 MDM2 CHEK2
4
DNA Double-Strand Break Repair 65
Show member pathways
 13.32 XPC TP53 MLH1 CHEK2 CHEK1 BRCA2
5
Cellular Senescence (REACTOME) 65
Show member pathways
 13.19 TP53 RB1 MDM2 CDKN2A CDKN1A ATM
6
PI3K-Akt signaling pathway 36
Show member pathways
 13.12 TP53 RB1 PTEN MDM2 EGFR CDKN1A
7
Regulation of TP53 Activity 65
Show member pathways
 13.11 TP53 PTEN MLH1 MDM2 CHEK2 CHEK1
8
Human cytomegalovirus infection 36
Show member pathways
 13.08 TP53 RB1 MDM2 EGFR CHEK1 CDKN2A
9
TCR Signaling (Qiagen) 63
Show member pathways
 13.03 XPC TP53 MLH1 CHEK2 BRCA2 BRCA1
10
Endometrial cancer 36
Show member pathways
 13.03 TP53 RB1 PTEN MLH1 MDM2 EGFR
11
Pathways in cancer 36
13.01 TP53 RB1 PTEN MLH1 MDM2 EGFR
12
Gastric cancer 36
Show member pathways
 12.92 TP53 RB1 PTEN MLH1 EGFR CDKN2A
13
Chks in Checkpoint Regulation 63
Show member pathways
 12.83 XPC TP53 RB1 MDM2 CHEK2 CHEK1
14
Downstream signaling events of B Cell Receptor (BCR) 65
Show member pathways
 12.79 TP53 PTEN MDM2 EGFR CDKN1A
15
Cell Cycle Checkpoints 65
Show member pathways
 12.78 TP53 MDM2 CHEK2 CHEK1 CDKN1A BRCA1
16
Apoptosis Modulation and Signaling 1
Show member pathways
 12.77 TP53 MDM2 CDKN2A CDKN1A ATM
17
ErbB signaling pathway 36 1
Show member pathways
 12.74 TP53 PTEN NF1 MDM2 EGFR CDKN1A
18
Mitotic G1-G1/S phases 65
Show member pathways
 12.7 TP53 RB1 MDM2 CDKN2A CDKN1A ATM
19
MicroRNAs in cancer 36
12.7 TP53 PTEN MDM2 EGFR CDKN2A CDKN1A
20
SUMOylation 65
Show member pathways
 12.66 XPC TP53 MDM2 CDKN2A BRCA1
21
Glioma 36
Show member pathways
 12.66 TP53 RB1 PTEN NF1 MDM2 EGFR
22
Apoptosis Pathway 70
Show member pathways
 12.59 TP53 MDM2 EGFR CHEK2 CHEK1 ATM
23
Cell cycle 36 1
12.53 TP53 RB1 MDM2 CHEK2 CHEK1 CDKN2A
24
Human T-cell leukemia virus 1 infection 36
12.5 TP53 RB1 PTEN CHEK2 CHEK1 CDKN2A
25
Cyclins and Cell Cycle Regulation 63
Show member pathways
 12.47 TP53 RB1 CDKN2A CDKN1A ATM
26
Translation Non-genomic (rapid) action of Androgen Receptor 22
Show member pathways
 12.47 TP53 PTEN MDM2 EGFR CDKN1A CAV1
27
Viral carcinogenesis 36
12.46 TP53 RB1 MDM2 CHEK1 CDKN2A CDKN1A
28
Shigellosis 36
12.44 TP53 MDM2 EGFR ATM
29
Development IGF-1 receptor signaling 22
Show member pathways
 12.44 TP53 PTEN MDM2 CDKN1A
30
Proteoglycans in cancer 36
12.43 TP53 MDM2 EGFR CDKN1A CAV1
31
DNA Double Strand Break Response 65
Show member pathways
 12.42 TP53 CHEK2 BRCA1 ATM
32
DNA Damage/Telomere Stress Induced Senescence 65
Show member pathways
 12.4 TP53 RB1 CDKN1A ATM
33
Cell cycle Role of SCF complex in cell cycle regulation 22
Show member pathways
 12.38 RB1 CHEK2 CHEK1 CDKN2A CDKN1A BRCA1
34
MAPK Signaling: Mitogens 64
Show member pathways
 12.36 TP53 RB1 PTEN MDM2 EGFR CDKN1A
35
p53 Signaling 63
Show member pathways
 12.36 TP53 RB1 PTEN MDM2 CHEK2 CHEK1
36
Homologous DNA Pairing and Strand Exchange 65
Show member pathways
 12.35 CHEK1 BRCA2 BRCA1 ATM
37
Transcriptional misregulation in cancer 36
12.33 TP53 MDM2 CDKN1A ATM
38
DNA Damage Response 1
Show member pathways
 12.33 TP53 RB1 PTEN MDM2 CHEK2 CHEK1
39
Colorectal Cancer Metastasis 63
12.26 TP53 MLH1 EGFR CDKN1A
40
FoxO signaling pathway 36
Show member pathways
 12.23 PTEN MDM2 EGFR CDKN1A ATM
41
Cellular senescence (KEGG) 36
12.21 TP53 RB1 PTEN MDM2 CHEK2 CHEK1
42
Direct p53 effectors 1
12.2 TP53 RB1 PTEN MLH1 MDM2 EGFR
43
DNA Damage Response (only ATM dependent) 1
12.18 TP53 PTEN MDM2 CDKN2A CDKN1A ATM
44
Senescence and Autophagy in Cancer 1
12.14 TP53 RB1 PTEN MDM2 CDKN2A CDKN1A
45
Glioblastoma Multiforme 63
12.1 TP53 RB1 PTEN NF1 MDM2 EGFR
46
Androgen receptor signaling pathway 1
12.05 RB1 PTEN MDM2 EGFR CDKN1A CAV1
47
ATM Pathway 63
Show member pathways
 12.02 TP53 MDM2 CHEK2 CHEK1 CDKN1A BRCA1
48
Retinoblastoma (RB) in Cancer 1
12.01 TP53 RB1 MDM2 CHEK1 CDKN1A
49
Small cell lung cancer 36
11.99 TP53 RB1 PTEN CDKN1A
50
BRCA1 Pathway 63
Show member pathways
 11.97 TP53 RB1 CHEK2 CHEK1 BRCA2 BRCA1
Sources

GO Terms for Li-Fraumeni Syndrome

About this section

Cellular components related to Li-Fraumeni Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.16 XPC WRAP53 TP53 RB1 PTEN NF1
2 nucleolus GO:0005730 9.98 XPC TP53 NF1 MDM2 CDKN2A CDKN1A
3 nuclear body GO:0016604 9.77 WRAP53 TP53 MDM2 CDKN1A BRCA1
4 PML body GO:0016605 9.62 TP53 RB1 PTEN CHEK2
5 condensed nuclear chromosome GO:0000794 9.58 MLH1 CHEK1 BRCA1
6 protein-containing complex GO:0032991 9.56 TP53 MDM2 EGFR CHEK1 CDKN1A CAV1
7 nucleoplasm GO:0005654 9.47 XPC WRAP53 TP53 RB1 PTEN MLH1
8 chromosome, telomeric region GO:0000781 9.46 WRAP53 CHEK2 CHEK1 ATM

Biological processes related to Li-Fraumeni Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 53)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 10.16 EGFR CHEK2 CHEK1 CDKN2A CDKN1A ATM
2 viral process GO:0016032 10.14 WRAP53 TP53 RB1 MDM2 EGFR CAV1
3 apoptotic process GO:0006915 10.13 TP53 RB1 PTEN CHEK2 CHEK1 CDKN2A
4 positive regulation of gene expression GO:0010628 10.12 TP53 PTEN MDM2 CDKN2A CAV1 BRCA1
5 positive regulation of transcription, DNA-templated GO:0045893 10.11 XPC TP53 RB1 EGFR CHEK2 CDKN2A
6 negative regulation of cell proliferation GO:0008285 10.09 TP53 RB1 PTEN NF1 CDKN2A CDKN1A
7 positive regulation of apoptotic process GO:0043065 10.08 TP53 PTEN NF1 CDKN2A ATM
8 response to drug GO:0042493 10.06 XPC TP53 PTEN MDM2 CDKN1A
9 regulation of cell proliferation GO:0042127 10.02 TP53 NF1 EGFR CHEK1 BRCA1
10 heart development GO:0007507 10.01 TP53 PTEN NF1 MDM2 CDKN1A ATM
11 protein stabilization GO:0050821 10 TP53 PTEN CHEK2 CDKN2A CDKN1A
12 regulation of cell cycle GO:0051726 9.98 TP53 RB1 PTEN CDKN1A ATM
13 cell cycle arrest GO:0007050 9.97 TP53 RB1 CDKN2A CDKN1A ATM
14 DNA repair GO:0006281 9.97 XPC WRAP53 MLH1 CHEK2 CHEK1 BRCA2
15 cell cycle GO:0007049 9.96 TP53 RB1 MLH1 CHEK2 CHEK1 CDKN2A
16 negative regulation of cell growth GO:0030308 9.95 TP53 RB1 CDKN2A CDKN1A
17 response to organic cyclic compound GO:0014070 9.94 PTEN IDH1 EGFR CDKN1A
18 regulation of signal transduction by p53 class mediator GO:1901796 9.91 TP53 MDM2 CHEK2 CHEK1 BRCA1 ATM
19 double-strand break repair GO:0006302 9.9 TP53 CHEK2 BRCA2 BRCA1
20 negative regulation of protein kinase activity GO:0006469 9.89 RB1 NF1 CDKN2A
21 double-strand break repair via homologous recombination GO:0000724 9.89 BRCA2 BRCA1 ATM
22 negative regulation of G1/S transition of mitotic cell cycle GO:2000134 9.89 RB1 PTEN CDKN2A CDKN1A
23 Ras protein signal transduction GO:0007265 9.88 TP53 RB1 NF1 CDKN2A CDKN1A
24 cellular response to drug GO:0035690 9.87 TP53 EGFR CHEK2
25 double-strand break repair via nonhomologous end joining GO:0006303 9.87 MLH1 BRCA1 ATM
26 positive regulation of neuron apoptotic process GO:0043525 9.86 TP53 NF1 ATM
27 nucleotide-excision repair GO:0006289 9.85 XPC TP53 BRCA2
28 neuron apoptotic process GO:0051402 9.85 TP53 RB1 ATM
29 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0006977 9.85 TP53 MDM2 CHEK2 CDKN1A ATM
30 cellular response to DNA damage stimulus GO:0006974 9.85 XPC WRAP53 TP53 MLH1 CHEK2 CHEK1
31 negative regulation of mitotic cell cycle GO:0045930 9.83 TP53 RB1 EGFR
32 DNA damage checkpoint GO:0000077 9.83 CHEK2 CHEK1 ATM
33 negative regulation of cyclin-dependent protein serine/threonine kinase activity GO:0045736 9.81 PTEN CDKN2A CDKN1A
34 positive regulation of DNA repair GO:0045739 9.81 WRAP53 EGFR BRCA1
35 response to gamma radiation GO:0010332 9.8 TP53 CHEK2 BRCA2
36 female gonad development GO:0008585 9.8 IDH1 BRCA2 ATM
37 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0042771 9.8 TP53 CHEK2 CDKN1A BRCA2
38 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 9.8 MLH1 CHEK2 BRCA2 BRCA1 ATM
39 response to X-ray GO:0010165 9.79 TP53 CDKN1A BRCA2
40 DNA damage induced protein phosphorylation GO:0006975 9.73 CHEK2 CHEK1 ATM
41 cellular response to gamma radiation GO:0071480 9.72 TP53 MDM2 CHEK2 CDKN1A ATM
42 amyloid fibril formation GO:1990000 9.71 MDM2 CDKN2A
43 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 9.71 TP53 EGFR
44 signal transduction involved in G2 DNA damage checkpoint GO:0072425 9.71 CHEK1 BRCA1
45 forebrain morphogenesis GO:0048853 9.7 PTEN NF1
46 meiotic telomere clustering GO:0045141 9.7 MLH1 ATM
47 negative regulation of neuroblast proliferation GO:0007406 9.69 TP53 NF1
48 cellular response to UV-C GO:0071494 9.69 TP53 MDM2
49 signal transduction by p53 class mediator GO:0072331 9.68 TP53 CDKN1A
50 chordate embryonic development GO:0043009 9.68 BRCA2 BRCA1

Molecular functions related to Li-Fraumeni Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 kinase activity GO:0016301 9.88 EGFR CHEK2 CHEK1 CDKN2A CDKN1A ATM
2 protein kinase binding GO:0019901 9.87 TP53 PTEN EGFR CHEK2 CDKN2A CDKN1A
3 protein-containing complex binding GO:0044877 9.85 XPC WRAP53 EGFR CDKN1A CAV1 ATM
4 enzyme binding GO:0019899 9.76 TP53 RB1 PTEN MLH1 MDM2 EGFR
5 identical protein binding GO:0042802 9.73 WRAP53 TP53 RB1 PTEN MDM2 IDH1
6 disordered domain specific binding GO:0097718 9.56 TP53 RB1 MDM2 CDKN2A
7 cyclin-dependent protein serine/threonine kinase inhibitor activity GO:0004861 9.43 CDKN2A CDKN1A
8 ubiquitin protein ligase binding GO:0031625 9.23 WRAP53 TP53 RB1 MDM2 EGFR CHEK2
Sources

Sources for Li-Fraumeni Syndrome

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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