HNPCC4
MCID: CLR039
MIFTS: 37

Colorectal Cancer, Hereditary Nonpolyposis, Type 4 (HNPCC4)

Categories: Cancer diseases, Gastrointestinal diseases, Genetic diseases

Aliases & Classifications for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

MalaCards integrated aliases for Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

Name: Colorectal Cancer, Hereditary Nonpolyposis, Type 4 57 13 73
Hereditary Nonpolyposis Colorectal Cancer Type 4 12 29 6 15
Hnpcc4 57 12 75
Cancer, Colorectal, Nonpolyposis, Hereditary, Type 4 40
Hereditary Non-Polyposis Colorectal Cancer 4 75

Characteristics:

HPO:

32
colorectal cancer, hereditary nonpolyposis, type 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 614337
Disease Ontology 12 DOID:0070275
MedGen 42 C1838333
MeSH 44 D003123
UMLS 73 C1838333

Summaries for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

UniProtKB/Swiss-Prot : 75 Hereditary non-polyposis colorectal cancer 4: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra- colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.

MalaCards based summary : Colorectal Cancer, Hereditary Nonpolyposis, Type 4, also known as hereditary nonpolyposis colorectal cancer type 4, is related to colorectal cancer, hereditary nonpolyposis, type 7 and spindle cell intraocular melanoma. An important gene associated with Colorectal Cancer, Hereditary Nonpolyposis, Type 4 is PMS2 (PMS1 Homolog 2, Mismatch Repair System Component), and among its related pathways/superpathways are Formation of HIV-1 elongation complex containing HIV-1 Tat and DNA Double-Strand Break Repair. Affiliated tissues include skin, colon and breast, and related phenotypes are ovarian neoplasm and endometrial carcinoma

Disease Ontology : 12 A Lynch syndrome that has material basis in heterozygous mutation in the PMS2 gene on chromosome 7p22.

Description from OMIM: 614337

Related Diseases for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Diseases in the Colorectal Cancer, Hereditary Nonpolyposis, Type 6 family:

Colorectal Cancer, Hereditary Nonpolyposis, Type 2 Colorectal Cancer, Hereditary Nonpolyposis, Type 8
Colorectal Cancer, Hereditary Nonpolyposis, Type 4 Colorectal Cancer, Hereditary Nonpolyposis, Type 5
Colorectal Cancer, Hereditary Nonpolyposis, Type 7

Diseases related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 colorectal cancer, hereditary nonpolyposis, type 7 31.5 MLH1 MSH2
2 spindle cell intraocular melanoma 10.0 MLH1 PMS2
3 adenoma 9.9 MLH1 MSH2
4 lower lip cancer 9.9 MLH1 MSH2
5 anal fistula 9.9 MLH1 MSH2
6 melanocytic nevus syndrome, congenital 9.9 MLH1 MSH2
7 childhood kidney cell carcinoma 9.9 MLH1 MSH2
8 cecum adenocarcinoma 9.9 MLH1 MSH2
9 intestinal benign neoplasm 9.9 MLH1 MSH2
10 keratoacanthoma 9.9 MLH1 MSH2
11 skin benign neoplasm 9.9 MLH1 MSH2
12 colorectal cancer, hereditary nonpolyposis, type 5 9.9 MLH1 MSH2
13 familial colorectal cancer 9.9 MLH1 MSH2
14 colorectal adenoma 9.9 MLH1 MSH2
15 colorectal adenocarcinoma 9.9 MLH1 MSH2
16 female reproductive system disease 9.9 MLH1 MSH2
17 rectal neoplasm 9.9 MLH1 MSH2
18 familial adenomatous polyposis 9.8 MLH1 MSH2
19 gastrointestinal system disease 9.8 MLH1 MSH2
20 ulcerative colitis 9.8 MLH1 MSH2
21 adamantinoma of long bones 9.8 MLH1 MSH2
22 appendix carcinoid tumor 9.7 MLH1 MSH2 PMS2
23 adenosquamous colon carcinoma 9.7 MLH1 MSH2 PMS2
24 sebaceous adenoma 9.7 MLH1 MSH2 PMS2
25 rhabdomyosarcoma 9.7 MSH2 PMS2
26 lynch syndrome i 9.7 MLH1 MSH2 PMS2
27 lynch syndrome 9.7 MLH1 MSH2 PMS2
28 sebaceous adenocarcinoma 9.7 MLH1 MSH2 PMS2
29 muir-torre syndrome 9.7 MLH1 MSH2 PMS2
30 small intestine cancer 9.7 MLH1 MSH2 PMS2
31 mismatch repair cancer syndrome 9.7 MLH1 MSH2 PMS2
32 uterine anomalies 9.7 MLH1 MSH2 PMS2
33 colonic disease 9.7 MLH1 MSH2 PMS2
34 autosomal genetic disease 9.7 MLH1 MSH2 PMS2
35 intestinal disease 9.7 MLH1 MSH2 PMS2
36 gastrointestinal system cancer 9.7 MLH1 MSH2 PMS2
37 autosomal dominant disease 9.7 MLH1 MSH2 PMS2
38 large intestine cancer 9.7 MLH1 MSH2 PMS2
39 endometrial cancer 9.7 MLH1 MSH2 PMS2
40 brain cancer 9.6 MSH2 PMS2

Graphical network of the top 20 diseases related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4:



Diseases related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Symptoms & Phenotypes for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Clinical features from OMIM:

614337

Human phenotypes related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

32
# Description HPO Frequency HPO Source Accession
1 ovarian neoplasm 32 HP:0100615
2 endometrial carcinoma 32 HP:0012114
3 hereditary nonpolyposis colorectal carcinoma 32 HP:0006716

GenomeRNAi Phenotypes related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.65 PMS2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.65 MSH2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-14 9.65 MSH2 PMS2
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.65 PMS2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.65 PMS2
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 9.65 PMS2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.65 MSH2
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-59 9.65 PMS2
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-98 9.65 PMS2
10 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.8 MLH1 MSH2 PMS2

MGI Mouse Phenotypes related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.13 MLH1 MSH2 PMS2
2 neoplasm MP:0002006 8.8 MLH1 MSH2 PMS2

Drugs & Therapeutics for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Search Clinical Trials , NIH Clinical Center for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Genetic Tests for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Genetic tests related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

# Genetic test Affiliating Genes
1 Hereditary Nonpolyposis Colorectal Cancer Type 4 29 PMS2

Anatomical Context for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

MalaCards organs/tissues related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

41
Skin, Colon, Breast, Ovary, Small Intestine, Uterus, Bone

Publications for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Variations for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

UniProtKB/Swiss-Prot genetic disease variations for Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

75
# Symbol AA change Variation ID SNP ID
1 PMS2 p.Glu705Lys VAR_012974 rs267608161
2 PMS2 p.Ser46Ile VAR_066838 rs121434629
3 PMS2 p.Ser46Asn VAR_078518 rs121434629
4 PMS2 p.Cys843Tyr VAR_078538 rs267608174

ClinVar genetic disease variations for Colorectal Cancer, Hereditary Nonpolyposis, Type 4:

6 (show top 50) (show all 338)
# Gene Variation Type Significance SNP ID Assembly Location
1 PMS2 NM_000535.6(PMS2): c.400C> T (p.Arg134Ter) single nucleotide variant Pathogenic rs63750871 GRCh37 Chromosome 7, 6042221: 6042221
2 PMS2 NM_000535.6(PMS2): c.400C> T (p.Arg134Ter) single nucleotide variant Pathogenic rs63750871 GRCh38 Chromosome 7, 6002590: 6002590
3 PMS2 NM_000535.6(PMS2): c.2404C> T (p.Arg802Ter) single nucleotide variant Pathogenic rs63751466 GRCh37 Chromosome 7, 6017260: 6017260
4 PMS2 NM_000535.6(PMS2): c.2404C> T (p.Arg802Ter) single nucleotide variant Pathogenic rs63751466 GRCh38 Chromosome 7, 5977629: 5977629
5 PMS2 NM_000535.6(PMS2): c.1021delA (p.Arg341Glyfs) deletion Pathogenic rs63750049 GRCh38 Chromosome 7, 5989923: 5989923
6 PMS2 NM_000535.6(PMS2): c.1021delA (p.Arg341Glyfs) deletion Pathogenic rs63750049 GRCh37 Chromosome 7, 6029554: 6029554
7 PMS2 NM_000535.6(PMS2): c.1882C> T (p.Arg628Ter) single nucleotide variant Pathogenic rs63750451 GRCh37 Chromosome 7, 6026514: 6026514
8 PMS2 NM_000535.6(PMS2): c.1882C> T (p.Arg628Ter) single nucleotide variant Pathogenic rs63750451 GRCh38 Chromosome 7, 5986883: 5986883
9 PMS2 NM_000535.6(PMS2): c.846delG (p.Ser283Valfs) deletion Pathogenic rs1057515571 GRCh38 Chromosome 7, 5995591: 5995591
10 PMS2 NM_000535.6(PMS2): c.846delG (p.Ser283Valfs) deletion Pathogenic rs1057515571 GRCh37 Chromosome 7, 6035222: 6035222
11 PMS2 NM_000535.6(PMS2): c.1731_1732delGCinsAGT (p.Arg578Valfs) indel Pathogenic/Likely pathogenic rs1057515572 GRCh38 Chromosome 7, 5987033: 5987034
12 PMS2 NM_000535.6(PMS2): c.1731_1732delGCinsAGT (p.Arg578Valfs) indel Pathogenic/Likely pathogenic rs1057515572 GRCh37 Chromosome 7, 6026664: 6026665
13 PMS2 NM_000535.6(PMS2): c.137G> T (p.Ser46Ile) single nucleotide variant Likely pathogenic rs121434629 GRCh37 Chromosome 7, 6045549: 6045549
14 PMS2 NM_000535.6(PMS2): c.137G> T (p.Ser46Ile) single nucleotide variant Likely pathogenic rs121434629 GRCh38 Chromosome 7, 6005918: 6005918
15 PMS2 NM_000535.6(PMS2): c.1408C> T (p.Pro470Ser) single nucleotide variant Benign rs1805321 GRCh37 Chromosome 7, 6026988: 6026988
16 PMS2 NM_000535.6(PMS2): c.1408C> T (p.Pro470Ser) single nucleotide variant Benign rs1805321 GRCh38 Chromosome 7, 5987357: 5987357
17 PMS2 NM_000535.6(PMS2): c.2007-7C> T single nucleotide variant Benign rs55954143 GRCh37 Chromosome 7, 6022629: 6022629
18 PMS2 NM_000535.6(PMS2): c.2007-7C> T single nucleotide variant Benign rs55954143 GRCh38 Chromosome 7, 5982998: 5982998
19 PMS2 NM_000535.6(PMS2): c.2253T> C (p.Phe751=) single nucleotide variant Benign rs1805325 GRCh37 Chromosome 7, 6018249: 6018249
20 PMS2 NM_000535.6(PMS2): c.2253T> C (p.Phe751=) single nucleotide variant Benign rs1805325 GRCh38 Chromosome 7, 5978618: 5978618
21 PMS2 NM_000535.6(PMS2): c.2324A> G (p.Asn775Ser) single nucleotide variant Benign rs17420802 GRCh37 Chromosome 7, 6017340: 6017340
22 PMS2 NM_000535.6(PMS2): c.2324A> G (p.Asn775Ser) single nucleotide variant Benign rs17420802 GRCh38 Chromosome 7, 5977709: 5977709
23 PMS2 NM_000535.6(PMS2): c.2570G> C (p.Gly857Ala) single nucleotide variant Benign rs1802683 GRCh37 Chromosome 7, 6013049: 6013049
24 PMS2 NM_000535.6(PMS2): c.2570G> C (p.Gly857Ala) single nucleotide variant Benign rs1802683 GRCh38 Chromosome 7, 5973418: 5973418
25 PMS2 NM_000535.6(PMS2): c.705+17A> G single nucleotide variant Benign rs62456182 GRCh37 Chromosome 7, 6038722: 6038722
26 PMS2 NM_000535.6(PMS2): c.705+17A> G single nucleotide variant Benign rs62456182 GRCh38 Chromosome 7, 5999091: 5999091
27 PMS2 NM_000535.6(PMS2): c.780C> G (p.Ser260=) single nucleotide variant Benign rs1805319 GRCh37 Chromosome 7, 6036980: 6036980
28 PMS2 NM_000535.6(PMS2): c.780C> G (p.Ser260=) single nucleotide variant Benign rs1805319 GRCh38 Chromosome 7, 5997349: 5997349
29 PMS2 NM_000535.6(PMS2): c.1437C> G (p.His479Gln) single nucleotide variant Uncertain significance rs63750685 GRCh37 Chromosome 7, 6026959: 6026959
30 PMS2 NM_000535.6(PMS2): c.1437C> G (p.His479Gln) single nucleotide variant Uncertain significance rs63750685 GRCh38 Chromosome 7, 5987328: 5987328
31 PMS2 NM_000535.6(PMS2): c.1454C> A (p.Thr485Lys) single nucleotide variant Benign rs1805323 GRCh37 Chromosome 7, 6026942: 6026942
32 PMS2 NM_000535.6(PMS2): c.1454C> A (p.Thr485Lys) single nucleotide variant Benign rs1805323 GRCh38 Chromosome 7, 5987311: 5987311
33 PMS2 NM_000535.6(PMS2): c.1531A> G (p.Thr511Ala) single nucleotide variant Benign rs2228007 GRCh37 Chromosome 7, 6026865: 6026865
34 PMS2 NM_000535.6(PMS2): c.1531A> G (p.Thr511Ala) single nucleotide variant Benign rs2228007 GRCh38 Chromosome 7, 5987234: 5987234
35 PMS2 NM_000535.6(PMS2): c.1532C> T (p.Thr511Met) single nucleotide variant Benign rs74902811 GRCh37 Chromosome 7, 6026864: 6026864
36 PMS2 NM_000535.6(PMS2): c.1532C> T (p.Thr511Met) single nucleotide variant Benign rs74902811 GRCh38 Chromosome 7, 5987233: 5987233
37 PMS2 NM_000535.6(PMS2): c.1688G> T (p.Arg563Leu) single nucleotide variant Likely benign rs63750668 GRCh37 Chromosome 7, 6026708: 6026708
38 PMS2 NM_000535.6(PMS2): c.1688G> T (p.Arg563Leu) single nucleotide variant Likely benign rs63750668 GRCh38 Chromosome 7, 5987077: 5987077
39 PMS2 NM_000535.6(PMS2): c.1711C> A (p.Leu571Ile) single nucleotide variant Likely benign rs63750055 GRCh37 Chromosome 7, 6026685: 6026685
40 PMS2 NM_000535.6(PMS2): c.1711C> A (p.Leu571Ile) single nucleotide variant Likely benign rs63750055 GRCh38 Chromosome 7, 5987054: 5987054
41 PMS2 NM_000535.6(PMS2): c.1789A> T (p.Thr597Ser) single nucleotide variant Benign rs1805318 GRCh37 Chromosome 7, 6026607: 6026607
42 PMS2 NM_000535.6(PMS2): c.1789A> T (p.Thr597Ser) single nucleotide variant Benign rs1805318 GRCh38 Chromosome 7, 5986976: 5986976
43 PMS2 NM_000535.6(PMS2): c.1866G> A (p.Met622Ile) single nucleotide variant Benign rs1805324 GRCh37 Chromosome 7, 6026530: 6026530
44 PMS2 NM_000535.6(PMS2): c.1866G> A (p.Met622Ile) single nucleotide variant Benign rs1805324 GRCh38 Chromosome 7, 5986899: 5986899
45 PMS2 NM_000535.6(PMS2): c.2149G> A (p.Val717Met) single nucleotide variant Conflicting interpretations of pathogenicity rs201671325 GRCh37 Chromosome 7, 6022480: 6022480
46 PMS2 NM_000535.6(PMS2): c.2149G> A (p.Val717Met) single nucleotide variant Conflicting interpretations of pathogenicity rs201671325 GRCh38 Chromosome 7, 5982849: 5982849
47 PMS2 NM_000535.6(PMS2): c.52A> G (p.Ile18Val) single nucleotide variant Likely benign rs63750123 GRCh37 Chromosome 7, 6045634: 6045634
48 PMS2 NM_000535.6(PMS2): c.52A> G (p.Ile18Val) single nucleotide variant Likely benign rs63750123 GRCh38 Chromosome 7, 6006003: 6006003
49 PMS2 NM_000535.6(PMS2): c.53T> C (p.Ile18Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs201343342 GRCh37 Chromosome 7, 6045633: 6045633
50 PMS2 NM_000535.6(PMS2): c.53T> C (p.Ile18Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs201343342 GRCh38 Chromosome 7, 6006002: 6006002

Expression for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Search GEO for disease gene expression data for Colorectal Cancer, Hereditary Nonpolyposis, Type 4.

Pathways for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Pathways related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4 according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.73 MLH1 MSH2 PMS2
2
Show member pathways
12.64 MLH1 MSH2 PMS2
3
Show member pathways
12.36 MLH1 MSH2 PMS2
4 12 MLH1 MSH2
5 11.71 MLH1 MSH2
6 11.45 MLH1 MSH2 PMS2
7 11.41 MLH1 PMS2
8 11.27 MLH1 MSH2
9
Show member pathways
11.12 MLH1 MSH2 PMS2
10 11.11 MLH1 MSH2
11
Show member pathways
10.97 MLH1 MSH2
12
Show member pathways
10.86 MLH1 MSH2
13 10.26 MLH1 MSH2 PMS2

GO Terms for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

Cellular components related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 MutLalpha complex GO:0032389 8.96 MLH1 PMS2
2 mismatch repair complex GO:0032300 8.8 MLH1 MSH2 PMS2

Biological processes related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.63 MLH1 MSH2 PMS2
2 DNA repair GO:0006281 9.61 MLH1 MSH2 PMS2
3 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 9.48 MLH1 MSH2
4 isotype switching GO:0045190 9.4 MLH1 MSH2
5 positive regulation of isotype switching to IgG isotypes GO:0048304 9.37 MLH1 MSH2
6 positive regulation of isotype switching to IgA isotypes GO:0048298 9.32 MLH1 MSH2
7 somatic recombination of immunoglobulin gene segments GO:0016447 9.26 MLH1 MSH2
8 somatic recombination of immunoglobulin genes involved in immune response GO:0002204 9.16 MLH1 MSH2
9 mismatch repair GO:0006298 9.13 MLH1 MSH2 PMS2
10 somatic hypermutation of immunoglobulin genes GO:0016446 8.8 MLH1 MSH2 PMS2

Molecular functions related to Colorectal Cancer, Hereditary Nonpolyposis, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.54 MLH1 MSH2 PMS2
2 ATPase activity GO:0016887 9.5 MLH1 MSH2 PMS2
3 MutSalpha complex binding GO:0032407 9.26 MLH1 PMS2
4 guanine/thymine mispair binding GO:0032137 9.16 MLH1 MSH2
5 single-stranded DNA binding GO:0003697 9.13 MLH1 MSH2 PMS2
6 mismatched DNA binding GO:0030983 8.8 MLH1 MSH2 PMS2

Sources for Colorectal Cancer, Hereditary Nonpolyposis, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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