Lynch Syndrome I (HNPCC1)

Categories: Gastrointestinal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Lynch Syndrome I

MalaCards integrated aliases for Lynch Syndrome I:

Name: Lynch Syndrome I 57 29 54 6
Colorectal Cancer, Hereditary Nonpolyposis, Type 1 57 13 70
Hnpcc1 57 12 72
Lynch Syndrome 1 12 15
Fcc1 57 12
Colorectal Cancer, Hereditary Nonpolyposis, Type 1; Hnpcc1 57
Cancer, Colorectal, Nonpolyposis, Hereditary, Type 1 39
Colorectal Cancer, Hereditary Nonpolyposis, Type 3 70
Colon Cancer, Familial Nonpolyposis, Type 1; Fcc1 57
Hereditary Nonpolyposis Colorectal Cancer Type 1 12
Hereditary Non-Polyposis Colorectal Cancer 1 72
Hereditary Non-Polyposis Colorectal Cancer 3 72
Hereditary Non-Polyposis Colon Cancer Type 2 70
Colon Cancer, Familial Nonpolyposis, Type 1 57
Familial Nonpolyposis Colon Cancer Type 1 12
Hereditary Nonpolyposis Colorectal Cancer 70
Lynch Cancer Family Syndrome 72
Lynch Syndrome Type Ii 72
Lynch Syndrome Type I 72
Lynch Syndrome 72
Hnpcc3 72
Coca1 57



57 (Updated 05-Apr-2021)
autosomal dominant


lynch syndrome i:
Inheritance autosomal dominant inheritance


External Ids:

Disease Ontology 12 DOID:0070271
OMIM® 57 120435
OMIM Phenotypic Series 57 PS120435
MeSH 44 D003123
SNOMED-CT via HPO 68 263681008 363406005
UMLS 70 C1333990 C1333991 C2936783 more

Summaries for Lynch Syndrome I

UniProtKB/Swiss-Prot : 72 Hereditary non-polyposis colorectal cancer 1: 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 : Lynch Syndrome I, also known as colorectal cancer, hereditary nonpolyposis, type 1, is related to mismatch repair cancer syndrome 1 and colorectal cancer, hereditary nonpolyposis, type 4. An important gene associated with Lynch Syndrome I is MSH2 (MutS Homolog 2), and among its related pathways/superpathways are Direct p53 effectors and Mismatch repair. The drugs Aspirin and Antibodies have been mentioned in the context of this disorder. Affiliated tissues include colon, ovary and small intestine, and related phenotypes are colon cancer and Decreased replication of vaccinia virus (VACV)

Disease Ontology : 12 A Lynch syndrome that has material basis in heterozygous mutations in the MSH2 gene on chromosome 2p21-p16.

OMIM® : 57 Hereditary nonpolyposis colorectal cancer (HNPCC) is subdivided into (1) Lynch syndrome I, or site-specific colonic cancer, and (2) Lynch syndrome II, or extracolonic cancer, particularly carcinoma of the stomach, endometrium (see 608089), biliary and pancreatic system, and urinary tract (Lynch and Lynch, 1979; Lynch et al., 1985; Mecklin and Jarvinen, 1991). HNPCC disorders show a proclivity to early onset, predominant proximal location of colon cancer, a dominant pattern of inheritance, an excess of multiple primary cancers, and significantly improved survival when compared stage for stage with the American College of Surgeons Audit Series. Lynch et al. (1991) estimated that hereditary nonpolyposis colorectal cancer accounts for about 4 to 6% of colorectal cancer. The minimum criterion of HNPCC is that colorectal carcinoma is diagnosed and histologically verified in at least 3 relatives belonging to 2 or more successive generations. Moreover, the age of onset should be less than 50 years in at least 1 patient. The Muir-Torre syndrome (MRTES; 158320) is a form of Lynch syndrome II associated with sebaceous skin tumors. (120435) (Updated 05-Apr-2021)

Wikipedia : 73 Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic... more...

Related Diseases for Lynch Syndrome I

Diseases in the Lynch Syndrome family:

Lynch Syndrome I

Diseases related to Lynch Syndrome I via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 291)
# Related Disease Score Top Affiliating Genes
1 mismatch repair cancer syndrome 1 32.5 PMS2 PMS1 MSH6 MSH2 MLH1
2 colorectal cancer, hereditary nonpolyposis, type 4 32.2 PMS2 PMS1 MLH1
3 muir-torre syndrome 32.2 PMS2 PMS1 MSH6 MSH2 MLH1 EPCAM
4 colorectal cancer, hereditary nonpolyposis, type 5 32.0 PMS2 MSH6 MSH2 MLH1
5 colorectal cancer, hereditary nonpolyposis, type 6 31.9 PMS2 PMS1 MSH6 MSH2 MLH1
6 colorectal cancer, hereditary nonpolyposis, type 2 31.8 USHBP1 MLH1 MCC CPZ AGBL5 AGBL4
7 familial adenomatous polyposis 31.2 PMS1 MSH6 MSH2 MLH1 MCC
8 colorectal adenocarcinoma 31.0 PMS2 MSH6 MSH2 MLH1
9 endometrial hyperplasia 30.9 MSH6 MSH2 MLH1
10 ascending colon cancer 30.8 MSH2 MLH1
11 transverse colon cancer 30.7 PMS2 MLH1
12 hereditary nonpolyposis colon cancer 30.7 PMS2 PMS1 MSH6 MSH2 MLH1 EPCAM
13 hereditary breast ovarian cancer syndrome 30.6 RAD51L3-RFFL RAD51D PMS2 PMS1 MSH6 MSH2
14 rectum adenocarcinoma 30.6 PMS2 MSH6 MSH2 MLH1
15 jejunal adenocarcinoma 30.5 PMS2 MSH6 MLH1
16 attenuated familial adenomatous polyposis 30.5 MSH6 MSH2
17 mismatch repair cancer syndrome 30.5 PMS2 MSH6 MSH2 MLH1
18 sebaceous adenoma 30.5 PMS2 MSH6 MSH2 MLH1
19 small intestine adenocarcinoma 30.5 PMS2 MSH6 MSH2 MLH1
20 duodenum adenocarcinoma 30.5 PMS2 MSH6 MSH2 MLH1
21 li-fraumeni syndrome 30.5 RAD51D PMS2 MSH6 MSH2 MLH1
22 duodenum cancer 30.5 PMS2 MSH6 MSH2 MLH1
23 neurofibromatosis 30.4 PMS2 MSH6 MSH2 MLH1
24 skin carcinoma 30.4 PMS2 MSH6 MSH2 MLH1 EPCAM
25 spindle cell intraocular melanoma 30.4 PMS2 MLH1
26 rectum cancer 30.4 MSH6 MSH2 MLH1
27 sebaceous adenocarcinoma 30.4 PMS2 PMS1 MSH6 MSH2 MLH1
28 lynch syndrome 30.3 RAD51L3-RFFL RAD51D PMS2 PMS1 MSH6 MSH2
29 colon adenocarcinoma 30.3 PMS2 MSH6 MLH1 EPCAM
30 jejunal cancer 30.2 PMS2 MSH6 MSH2 MLH1
31 endometrioid ovary carcinoma 30.2 MSH6 MLH1
32 juvenile polyposis syndrome 30.2 PMS2 MSH6 MSH2 MLH1
33 oligodendroglioma 30.2 PMS2 MSH6 MSH2 MLH1
34 small intestine cancer 30.1 PMS2 MSH6 MSH2 MLH1 EPCAM
35 gastric cancer, hereditary diffuse 30.0 RAD51D PMS2 MSH6 MSH2 MLH1 EPCAM
36 fanconi anemia, complementation group a 30.0 RAD51D PMS2 MSH6 MSH2 MLH1
37 cowden syndrome 29.9 RAD51D PMS2 PMS1 MSH6 MSH2 MLH1
38 ovarian cancer 11.2
39 pancreatic cancer 11.0
40 colorectal cancer, hereditary nonpolyposis, type 8 11.0
41 colorectal cancer, hereditary nonpolyposis, type 7 11.0
42 inherited cancer-predisposing syndrome 10.9
43 tumor predisposition syndrome 10.9
44 cutaneous telangiectasia and cancer syndrome, familial 10.9
45 gastric cancer 10.9
46 46,xy disorder of sexual development due to dihydrotestosterone backdoor pathway biosynthesis defect 10.9
47 colorectal cancer 10.9
48 adenoma 10.8
49 familial colorectal cancer 10.6
50 colorectal adenoma 10.6

Graphical network of the top 20 diseases related to Lynch Syndrome I:

Diseases related to Lynch Syndrome I

Symptoms & Phenotypes for Lynch Syndrome I

Human phenotypes related to Lynch Syndrome I:

# Description HPO Frequency HPO Source Accession
1 colon cancer 31 HP:0003003

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
nonpolyposis colon cancer

Clinical features from OMIM®:

120435 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Lynch Syndrome I according to GeneCards Suite gene sharing:

# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased replication of vaccinia virus (VACV) GR00362-A 8.32 CCL13

MGI Mouse Phenotypes related to Lynch Syndrome I:

# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.77 AGBL4 AGBL5 CCL13 DNAJC2 EPCAM MLH1
2 digestive/alimentary MP:0005381 9.76 CCL13 EPCAM MCC MLH1 MORC2 MSH2
3 neoplasm MP:0002006 9.17 CCL13 MCC MLH1 MSH2 MSH6 PMS1

Drugs & Therapeutics for Lynch Syndrome I

Drugs for Lynch Syndrome I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 33)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Aspirin Approved, Vet_approved Phase 3 50-78-2 2244
2 Antibodies Phase 3
3 Immunoglobulins Phase 3
4 Acetylsalicylic acid lysinate Phase 3
5 Fibrinolytic Agents Phase 3
6 Cyclooxygenase Inhibitors Phase 3
7 Antipyretics Phase 3
8 Platelet Aggregation Inhibitors Phase 3
nivolumab Approved Phase 2 946414-94-4
Aminosalicylic Acid Approved Phase 2 65-49-6 4649
11 Omega 3 Fatty Acid Phase 2
12 Cola Phase 2
13 Immunologic Factors Phase 1, Phase 2
14 Vaccines Phase 1, Phase 2
15 Antineoplastic Agents, Immunological Phase 2
16 Analgesics, Non-Narcotic Phase 2
17 Analgesics Phase 2
18 Antirheumatic Agents Phase 2
19 Anti-Inflammatory Agents Phase 2
20 Anti-Inflammatory Agents, Non-Steroidal Phase 2
21 Mesalamine Phase 2 89-57-6
22 Anti-Bacterial Agents Phase 2
23 Anti-Infective Agents Phase 2
24 Antitubercular Agents Phase 2
Naproxen Approved, Vet_approved Phase 1 22204-53-1 1302 156391
Caffeine Approved 58-08-2 2519
Atorvastatin Approved Early Phase 1 134523-00-5 60823
Sage Approved
29 Hydroxymethylglutaryl-CoA Reductase Inhibitors Early Phase 1
30 Anticholesteremic Agents Early Phase 1
31 Antimetabolites Early Phase 1
32 Lipid Regulating Agents Early Phase 1
33 Hypolipidemic Agents Early Phase 1

Interventional clinical trials:

(show all 43)
# Name Status NCT ID Phase Drugs
1 Assessment of the Effect of a Daily Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome Recruiting NCT02813824 Phase 3 Acetylsalicylic acid lysinate 300 mg;Placebo (for Aspirin 300);Acetylsalicylic acid lysinate 100 mg;Placebo 100 (for Aspirin 100)
2 PD-1 Antibody for the Prevention of Adenomatous Polyps and Second Primary Tumors in Patients With Lynch Syndrome: An Open-label, Multicenter, Randomized Controlled Clinical Trial Recruiting NCT04711434 Phase 3 PD-1 Antibody
3 A Randomised Double Blind Dose Non-inferiority Trial of a Daily Dose of 600mg Versus 300mg Versus 100mg of Enteric Coated Aspirin as a Cancer Preventive in Carriers of a Germline Pathological Mismatch Repair Gene Defect, Lynch Syndrome Not yet recruiting NCT02497820 Phase 3 Aspirin
4 Early Detection of Pre-cancer Lesions in Adults With Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Syndrome: Assessment of Coloscopy With Chromoscopy Benefit Completed NCT00224601 Phase 2
5 Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE) Recruiting NCT03831698 Phase 2 Omega-3 fatty acid ethyl esters (2 gram)
6 Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI Active, not recruiting NCT01885702 Phase 1, Phase 2
7 A Phase II Study of PD-1 Inhibition for the Prevention of Colon Adenomas in Patients With Lynch Syndrome and a History of Partial Colectomy Active, not recruiting NCT03631641 Phase 2
8 Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome - MesaCAPP Terminated NCT03070574 Phase 2 mesalamine 2400 MG (5-ASA);mesalamine 1200 MG
9 A Phase Ib Biomarker Trial of Naproxen in Patients at Risk for DNA Mismatch Repair Deficient Colorectal Cancer Completed NCT02052908 Phase 1 Naproxen
10 Hereditary Nonpolyposis Colorectal Cancer in Taiwan-Related Genetic Study and Clinical Applications Unknown status NCT00262171
11 Cohort Study of Universal Screening for Lynch Syndrome in Chinese Patients of Endometrial Cancer Unknown status NCT03291106
12 Predictive Factor Study of the Occurrence of Endometrial Cancer in Patients With Lynch Syndrome: Study Conducted in the Hauts-de-France Completed NCT04452266
13 Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes Completed NCT02198092
14 Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Colorectal Cancer Patients Meeting Chinese Lynch Syndrome Criteria: An Open-label and Multi-center Study. Completed NCT03046849
15 Ohio Colorectal Cancer Prevention Initiative: Universal Screening for Lynch Syndrome Completed NCT01850654
16 Diagnosis of Lynch Syndrome Based on the Colorectal Core™ Platform in Colorectal Cancer Patients With the Loss of Staining by Immunohistochemistry (IHC) of Any of the Mismatch Repair (MMR) Proteins: An Open-label and Multi-center Study Completed NCT03047226
17 High Definition White-Light Colonoscopy Versus Chromoendoscopy for Surveillance of Lynch Syndrome. A Prospective, Multicenter and Randomized Study Completed NCT02951390
18 Capsule Endoscopy in Lynch Syndrome for Small Intestinal Tumor Screening Completed NCT00898768 Early Phase 1
19 Linked Color Imaging Versus High-definition White Light Endoscopy for the Detection of Polyps in Patients With Lynch Syndrome. An International, Multicenter, Parallel Randomized Controlled Trial. Completed NCT03344289
20 Hereditary Colorectal and Associated Tumor Registry Study Completed NCT00633607
21 Chromoendoscopy in Lynch Syndrome Patients Completed NCT00905710
22 Comparison of Colonoscopy With Virtual Chromoendoscopy Using 3rd Generation NBI System to Chromoendoscopy With Indigo Carmine in Lynch Patients. Completed NCT02570516
23 Molecular Screening for Lynch Syndrome in Denmark Completed NCT01845753
24 Molecular Screening for Lynch Syndrome in Southern Denmark Completed NCT01216930
25 Integrating Genetic Testing for Lynch Syndrome in a Managed Care Setting Completed NCT01582841
26 Living in Lynch Syndrome Limbo: Exploring the Meaning of Uncertain Genetic Test Results Completed NCT01646112
27 Registry for Women Who Are At Risk Or May Have Lynch Syndrome Recruiting NCT00508573
28 Risk-Reducing Surgeries of Salpingo-oophorectomy With/Without Hysterectomy for Carriers With Mutation Genes of Hereditary Ovarian Cancer Recruiting NCT03294343
29 Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes Recruiting NCT02371135
30 Adherence to Comprehensive, Multi-Organ Screening Recommendations in Patients With Lynch Syndrome Recruiting NCT00582296
31 Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study Recruiting NCT04379999 Early Phase 1 Atorvastatin 20mg;Atorvastatin 20mg AND Aspirin 325 mg
32 The GEOLynch Cohort Study: Genetic, Environmental and Other Factors That Influence Tumour Risk Among Persons With Lynch Syndrome Recruiting NCT03303833
33 Systems-Level Capture of Family History Data to Assess Risk of Cancer Recruiting NCT04145388
34 Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland Recruiting NCT03124212
35 HEALTH4Families: Optimizing a Weight Management and Health Behavior Intervention for BRCA+ and Lynch Syndrome Families Recruiting NCT04125914
36 Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer Active, not recruiting NCT02494791
37 A Social Media Approach to Improve Genetic Risk Communication Phase I Active, not recruiting NCT01645904
38 Cancer Survivorship in Lynch Syndrome: Impact on Patients and Families Active, not recruiting NCT01126840
39 Randomized Trial to Determine Whether eConsent is Non-Inferior to Standard Consent Among Prospective Biobank Participants Enrolling by invitation NCT04131062
40 Specialized Program of Research Excellence (SPORE) in Endometrial Cancer Not yet recruiting NCT01199250
41 Evaluating the Cologuard Test for Use in Lynch Syndrome Not yet recruiting NCT04778566
42 Faecal Microbiota Characterization in Lynch Syndrome (LS) Patients With or Without Colorectal Neoplasia ( AAS-Lynch-Microbiote) Not yet recruiting NCT04791644
43 Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome Not yet recruiting NCT04508764

Search NIH Clinical Center for Lynch Syndrome I

Genetic Tests for Lynch Syndrome I

Genetic tests related to Lynch Syndrome I:

# Genetic test Affiliating Genes
1 Lynch Syndrome I 29 MSH2 PMS1

Anatomical Context for Lynch Syndrome I

MalaCards organs/tissues related to Lynch Syndrome I:

Colon, Ovary, Small Intestine, Breast, Uterus, Prostate, Brain

Publications for Lynch Syndrome I

Articles related to Lynch Syndrome I:

(show top 50) (show all 955)
# Title Authors PMID Year
Prostate cancer incidence in males with Lynch syndrome. 57 6
24434690 2014
Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers. 6 57
20587412 2010
Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. 57 6
20591884 2010
Germ line MLH1 and MSH2 mutations in Taiwanese Lynch syndrome families: characterization of a founder genomic mutation in the MLH1 gene. 6 57
19419416 2009
Germline novel MSH2 deletions and a founder MSH2 deletion associated with anticipation effects in HNPCC. 6 57
17250661 2007
Molecular characterization of the spectrum of genomic deletions in the mismatch repair genes MSH2, MLH1, MSH6, and PMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC). 6 57
15942939 2005
Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). 6 57
15872200 2005
Spectrum of genetic alterations in Muir-Torre syndrome is the same as in HNPCC. 6 57
14994245 2004
A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States. 6 57
14871915 2004
Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA. 57 6
14635101 2003
Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. 57 6
12658575 2003
Cancer risk in 348 French MSH2 or MLH1 gene carriers. 57 6
12624141 2003
A modified multiplex PCR assay for detection of large deletions in MSH2 and MLH1. 57 6
11857745 2002
Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing. 57 6
11839723 2002
Frequency of hereditary non-polyposis colorectal cancer in Danish colorectal cancer patients. 6 57
11772966 2002
The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. 57 6
11524701 2001
Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds. 6 57
11112663 2001
Conversion of diploidy to haploidy. 6 57
10693791 2000
New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. 6 57
10348829 1999
Mismatch repair gene defects contribute to the genetic basis of double primary cancers of the colorectum and endometrium. 6 57
10196371 1999
Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes. 6 57
9218993 1997
Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. 6 57
8574961 1996
Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. 57 6
8261515 1993
Constitutive deficiency in DNA mismatch repair: is it time for Lynch III? 61 57
17539898 2007
Constitutive deficiency in DNA mismatch repair. 61 57
17539897 2007
GSTM1 and GSTT1 polymorphisms as modifiers of age at diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) in a homogeneous cohort of individuals carrying a single predisposing mutation. 6 54
17087981 2006
Reduced frequency of extracolonic cancers in hereditary nonpolyposis colorectal cancer families with monoallelic hMLH1 expression. 61 6
9245993 1997
Hereditary nonpolyposis colorectal cancer (Lynch syndromes I & II). Genetics, pathology, natural history, and cancer control, Part I. 57 61
1648437 1991
Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies. 61 57
4016686 1985
Identification of MLH2/hPMS1 dominant mutations that prevent DNA mismatch repair function. 6
33303966 2020
Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome. 6
31992580 2020
Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome. 6
31965077 2020
Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer. 6
32587781 2020
Retained mismatch repair protein expression occurs in approximately 6% of microsatellite instability-high cancers and is associated with missense mutations in mismatch repair genes. 6
31857677 2020
High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers. 6
31494577 2020
Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics. 6
32002723 2020
The spectrum of Lynch syndrome-associated germ-line mutations in Russia. 6
31491536 2020
NOTCH and DNA repair pathways are more frequently targeted by genomic alterations in inflammatory than in non-inflammatory breast cancers. 6
31854063 2020
One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene. 6
31300551 2020
Development and Validation of a 34-Gene Inherited Cancer Predisposition Panel Using Next-Generation Sequencing. 6
32090079 2020
Mastermind: A Comprehensive Genomic Association Search Engine for Empirical Evidence Curation and Genetic Variant Interpretation. 6
33281875 2020
Contribution of mRNA Splicing to Mismatch Repair Gene Sequence Variant Interpretation. 6
32849802 2020
Tumour characteristics provide evidence for germline mismatch repair missense variant pathogenicity. 6
31391288 2020
An alternative approach to establishing unbiased colorectal cancer risk estimation in Lynch syndrome. 6
31204389 2019
Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome. 6
31697235 2019
Screening for Lynch Syndrome by Immunohistochemistry of Mismatch Repair Proteins: Significance of Indeterminate Result and Correlation With Mutational Studies. 6
30917047 2019
Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer. 6
31642931 2019
Methylation Tolerance-Based Functional Assay to Assess Variants of Unknown Significance in the MLH1 and MSH2 Genes and Identify Patients With Lynch Syndrome. 6
30998989 2019
A functional assay-based procedure to classify mismatch repair gene variants in Lynch syndrome. 6
30504929 2019
Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome. 6
30877237 2019

Variations for Lynch Syndrome I

ClinVar genetic disease variations for Lynch Syndrome I:

6 (show top 50) (show all 9405)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MLH1 NM_001354621.1(MLH1):c.-84del Deletion Pathogenic 455463 rs1553648023 GRCh37: 3:37061856-37061856
GRCh38: 3:37020365-37020365
2 MSH6 NM_000179.2(MSH6):c.1969del (p.Gln657fs) Deletion Pathogenic 234761 rs876661205 GRCh37: 2:48027088-48027088
GRCh38: 2:47799949-47799949
3 MSH6 NM_000179.3(MSH6):c.1634_1635del (p.Lys545fs) Deletion Pathogenic 140961 rs267608064 GRCh37: 2:48026753-48026754
GRCh38: 2:47799614-47799615
4 PMS2 NM_000535.7(PMS2):c.862_863del (p.Gln288fs) Deletion Pathogenic 91376 rs63750246 GRCh37: 7:6035205-6035206
GRCh38: 7:5995574-5995575
5 MLH1 NM_000249.3(MLH1):c.207+1G>A SNV Pathogenic 90020 rs267607718 GRCh37: 3:37038201-37038201
GRCh38: 3:36996710-36996710
6 MLH1 NM_000249.3(MLH1):c.885-2A>G SNV Pathogenic 90421 rs267607805 GRCh37: 3:37061799-37061799
GRCh38: 3:37020308-37020308
7 PMS2 NM_000535.7(PMS2):c.765C>A (p.Tyr255Ter) SNV Pathogenic 183716 rs573125799 GRCh37: 7:6036995-6036995
GRCh38: 7:5997364-5997364
8 MSH6 NM_000179.3(MSH6):c.1805C>G (p.Ser602Ter) SNV Pathogenic 182659 rs730881816 GRCh37: 2:48026927-48026927
GRCh38: 2:47799788-47799788
9 MSH2 NM_000251.2(MSH2):c.892C>T (p.Gln298Ter) SNV Pathogenic 91239 rs63750934 GRCh37: 2:47641507-47641507
GRCh38: 2:47414368-47414368
10 PMS2 NM_000535.7(PMS2):c.1376C>G (p.Ser459Ter) SNV Pathogenic 393103 rs587780724 GRCh37: 7:6027020-6027020
GRCh38: 7:5987389-5987389
11 MSH2 NM_000251.2(MSH2):c.362del (p.Tyr121fs) Deletion Pathogenic 428487 rs1114167831 GRCh37: 2:47635690-47635690
GRCh38: 2:47408551-47408551
12 MSH6 NM_000179.2(MSH6):c.3436C>T (p.Gln1146Ter) SNV Pathogenic 89382 rs63750356 GRCh37: 2:48030822-48030822
GRCh38: 2:47803683-47803683
13 MSH6 NM_000179.2(MSH6):c.3439-1G>T SNV Pathogenic 89390 rs587779263 GRCh37: 2:48032048-48032048
GRCh38: 2:47804909-47804909
14 MSH2 NM_000251.2(MSH2):c.1565_1568del (p.Tyr522fs) Deletion Pathogenic 418979 rs1064793561 GRCh37: 2:47693849-47693852
GRCh38: 2:47466710-47466713
15 MLH1 NM_000249.3(MLH1):c.589C>T (p.Gln197Ter) SNV Pathogenic 479670 rs1553644123 GRCh37: 3:37053502-37053502
GRCh38: 3:37012011-37012011
16 PMS2 NM_000535.7(PMS2):c.655G>T (p.Gly219Ter) SNV Pathogenic 423043 rs1064796190 GRCh37: 7:6038789-6038789
GRCh38: 7:5999158-5999158
17 MSH2 NM_000251.2(MSH2):c.873_876del (p.Thr292fs) Deletion Pathogenic 91236 rs587779191 GRCh37: 2:47641485-47641488
GRCh38: 2:47414346-47414349
18 MSH6 NM_000179.2(MSH6):c.3743_3744insT (p.Tyr1249fs) Insertion Pathogenic 183794 rs786201084 GRCh37: 2:48033439-48033440
GRCh38: 2:47806300-47806301
19 MLH1 NM_001167617.2(MLH1):c.-7del Deletion Pathogenic 421912 rs1064795441 GRCh37: 3:37042519-37042519
GRCh38: 3:37001028-37001028
20 MSH6 NM_001281492.1(MSH6):c.1689dup (p.Cys564fs) Duplication Pathogenic 187516 rs267608083 GRCh37: 2:48027195-48027196
GRCh38: 2:47800056-47800057
21 PMS2 NM_000535.7(PMS2):c.24-12_107delinsAAAT Indel Pathogenic 91341 rs1554306445 GRCh37: 7:6045579-6045674
GRCh38: 7:6005948-6006043
22 PMS2 NM_000535.7(PMS2):c.2361_2364del (p.Phe788fs) Deletion Pathogenic 91338 rs267608160 GRCh37: 7:6017300-6017303
GRCh38: 7:5977669-5977672
23 MSH6 NM_001281492.1(MSH6):c.2878_2884del (p.Glu960fs) Deletion Pathogenic 89366 rs587779259 GRCh37: 2:48030650-48030656
GRCh38: 2:47803511-47803517
24 MSH6 NM_001281492.1(MSH6):c.1244_1247del (p.Lys415fs) Deletion Pathogenic 89211 rs63749874 GRCh37: 2:48026755-48026758
GRCh38: 2:47799616-47799619
25 MLH1 NM_000249.3(MLH1):c.209_215delAAGAAGA Deletion Pathogenic 182513 rs730881734 GRCh37: 3:37042444-37042450
GRCh38: 3:37000953-37000959
26 MLH1 NM_000249.3(MLH1):c.1997G>A (p.Trp666Ter) SNV Pathogenic 265246 rs886039424 GRCh37: 3:37090402-37090402
GRCh38: 3:37048911-37048911
27 MSH2 NM_000251.2(MSH2):c.2334C>A (p.Cys778Ter) SNV Pathogenic 90956 rs63750618 GRCh37: 2:47705534-47705534
GRCh38: 2:47478395-47478395
28 MLH1 NM_000249.3(MLH1):c.55A>T (p.Ile19Phe) SNV Pathogenic 90274 rs63750648 GRCh37: 3:37035093-37035093
GRCh38: 3:36993602-36993602
29 MLH1 NM_001167618.2(MLH1):c.-221dup Duplication Pathogenic 90250 rs63749959 GRCh37: 3:37050348-37050349
GRCh38: 3:37008857-37008858
30 MSH6 NM_000179.3(MSH6):c.3573dup (p.Val1192fs) Duplication Pathogenic 372414 rs1057517764 GRCh37: 2:48032767-48032768
GRCh38: 2:47805628-47805629
31 MLH1 NM_000249.3(MLH1):c.1896+1G>T SNV Pathogenic 89926 rs267607867 GRCh37: 3:37089175-37089175
GRCh38: 3:37047684-37047684
32 MSH6 NM_001281492.1(MSH6):c.962del (p.Phe321fs) Deletion Pathogenic 224534 rs869312769 GRCh37: 2:48026473-48026473
GRCh38: 2:47799334-47799334
33 MSH2 NM_000251.2(MSH2):c.226C>T (p.Gln76Ter) SNV Pathogenic 90945 rs63750042 GRCh37: 2:47635554-47635554
GRCh38: 2:47408415-47408415
34 MSH2 NM_000251.3(MSH2):c.387_388del Microsatellite Pathogenic 91089 rs63750924 GRCh37: 2:47637247-47637248
GRCh38: 2:47410108-47410109
35 MLH1 NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter) SNV Pathogenic 371799 rs1057517541 GRCh37: 3:37067308-37067308
GRCh38: 3:37025817-37025817
36 MSH6 NM_001281492.1(MSH6):c.3414dup (p.Cys1139fs) Duplication Pathogenic 89469 rs267608118 GRCh37: 2:48033592-48033593
GRCh38: 2:47806453-47806454
37 MSH2 NM_000251.2(MSH2):c.1229del (p.Gly410fs) Deletion Pathogenic 545842 rs1553356700 GRCh37: 2:47657031-47657031
GRCh38: 2:47429892-47429892
38 MSH6 NM_000179.2(MSH6):c.1933G>T (p.Glu645Ter) SNV Pathogenic 422153 rs1064795591 GRCh37: 2:48027055-48027055
GRCh38: 2:47799916-47799916
39 MLH1 NM_000249.3(MLH1):c.67dup (p.Glu23fs) Duplication Pathogenic 422508 rs63750822 GRCh37: 3:37035100-37035101
GRCh38: 3:36993609-36993610
40 MSH6 NM_000179.2(MSH6):c.2269_2270del (p.Thr757fs) Deletion Pathogenic 234448 rs876661025 GRCh37: 2:48027391-48027392
GRCh38: 2:47800252-47800253
41 PMS2 NM_000535.7(PMS2):c.248T>G (p.Leu83Ter) SNV Pathogenic 419752 rs1064794083 GRCh37: 7:6043605-6043605
GRCh38: 7:6003974-6003974
42 MSH6 NM_000179.3(MSH6):c.3753_3756dup (p.Val1253fs) Duplication Pathogenic 234794 rs876661222 GRCh37: 2:48033448-48033449
GRCh38: 2:47806309-47806310
43 MSH6 NM_000179.2(MSH6):c.599C>G (p.Ser200Ter) SNV Pathogenic 234621 rs63751077 GRCh37: 2:48023174-48023174
GRCh38: 2:47796035-47796035
44 MSH6 NM_001281492.1(MSH6):c.3530_3537dup (p.Glu1180fs) Duplication Pathogenic 89481 rs587779295 GRCh37: 2:48033707-48033708
GRCh38: 2:47806568-47806569
45 MLH1 NM_001354630.1(MLH1):c.1732-958_1732-955del Deletion Pathogenic 89886 rs63749868 GRCh37: 3:37089047-37089050
GRCh38: 3:37047556-37047559
46 MLH1 NM_000249.3(MLH1):c.116+5G>C SNV Pathogenic 89658 rs267607710 GRCh37: 3:37035159-37035159
GRCh38: 3:36993668-36993668
47 PMS2 NM_000535.7(PMS2):c.1532del (p.Thr511fs) Deletion Pathogenic 545777 rs1554297636 GRCh37: 7:6026864-6026864
GRCh38: 7:5987233-5987233
48 MSH6 NM_001281492.1(MSH6):c.3488_3491dup (p.Pro1165fs) Duplication Pathogenic 418332 rs1553333500 GRCh37: 2:48033665-48033666
GRCh38: 2:47806526-47806527
49 MSH2 NM_000251.2(MSH2):c.212-1G>A SNV Pathogenic 90892 rs267607914 GRCh37: 2:47635539-47635539
GRCh38: 2:47408400-47408400
50 MSH6 NM_000179.2(MSH6):c.2690dup (p.Asn897fs) Duplication Pathogenic 420121 rs1553414010 GRCh37: 2:48027806-48027807
GRCh38: 2:47800667-47800668

UniProtKB/Swiss-Prot genetic disease variations for Lynch Syndrome I:

72 (show top 50) (show all 69)
# Symbol AA change Variation ID SNP ID
1 MSH2 p.His46Gln VAR_004470 rs33946261
2 MSH2 p.Asn139Ser VAR_004472 rs155335067
3 MSH2 p.Asp167His VAR_004474 rs63750255
4 MSH2 p.Ala305Thr VAR_004476 rs63751454
5 MSH2 p.Arg524Pro VAR_004479 rs63751207
6 MSH2 p.Glu562Val VAR_004480 rs63750997
7 MSH2 p.Pro622Leu VAR_004482 rs28929483
8 MSH2 p.His639Tyr VAR_004483 rs28929484
9 MSH2 p.Gly674Ser VAR_004485 rs63750234
10 MSH2 p.Cys697Phe VAR_004486 rs63750398
11 MSH2 p.Ala834Thr VAR_004488 rs63750757
12 MSH2 p.Gly692Arg VAR_009250 rs63750232
13 MSH2 p.Cys697Arg VAR_009251 rs63750961
14 MSH2 p.Val161Asp VAR_012936 rs63750126
15 MSH2 p.Asp506Tyr VAR_012941 rs63750492
16 MSH2 p.Ala636Pro VAR_012944 rs63750875
17 MSH2 p.Met688Ile VAR_012945 rs63750790
18 MSH2 p.Lys845Glu VAR_013172 rs63750571
19 MSH2 p.Asn127Ser VAR_019234 rs17217772
20 MSH2 p.Val163Gly VAR_022670 rs63750214
21 MSH2 p.Asp660Gly VAR_022671 rs108530805
22 MSH2 p.Thr33Pro VAR_043738 rs63751107
23 MSH2 p.Leu93Phe VAR_043743 rs63751429
24 MSH2 p.Val102Ile VAR_043745 rs193922373
25 MSH2 p.Lys110Thr VAR_043746
26 MSH2 p.Gly162Arg VAR_043747 rs63750624
27 MSH2 p.Val163Asp VAR_043748 rs63750214
28 MSH2 p.Gly164Arg VAR_043749 rs63750582
29 MSH2 p.Leu173Pro VAR_043751 rs63750070
30 MSH2 p.Leu175Pro VAR_043752 rs63751291
31 MSH2 p.Leu187Pro VAR_043753 rs63751444
32 MSH2 p.Asp283Tyr VAR_043757 rs63750381
33 MSH2 p.Cys333Tyr VAR_043759 rs63750828
34 MSH2 p.Pro336Ser VAR_043761 rs63751062
35 MSH2 p.Pro349Leu VAR_043763 rs587779067
36 MSH2 p.Arg359Ser VAR_043764 rs63751617
37 MSH2 p.Lys393Met VAR_043765 rs155847849
38 MSH2 p.Met492Val VAR_043767
39 MSH2 p.Thr552Pro VAR_043768 rs63750838
40 MSH2 p.Asn583Ser VAR_043770 rs201118107
41 MSH2 p.Ala600Val VAR_043771 rs63751236
42 MSH2 p.Asp603Asn VAR_043772 rs63750657
43 MSH2 p.His639Arg VAR_043775 rs587779116
44 MSH2 p.Glu647Lys VAR_043776
45 MSH2 p.Tyr656His VAR_043777
46 MSH2 p.Ile679Thr VAR_043779
47 MSH2 p.Ser723Phe VAR_043781 rs63750794
48 MSH2 p.Met729Val VAR_043782 rs155852005
49 MSH2 p.Thr732Ile VAR_043783 rs730881765
50 MSH2 p.Glu749Lys VAR_043785 rs63751477

Expression for Lynch Syndrome I

Search GEO for disease gene expression data for Lynch Syndrome I.

Pathways for Lynch Syndrome I

Pathways related to Lynch Syndrome I according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.55 PMS2 MSH2 MLH1
Show member pathways
11.33 PMS2 PMS1 MSH6 MSH2 MLH1
3 11.2 MSH6 MSH2 MLH1
4 10.39 PMS2 MSH6 MSH2 MLH1

GO Terms for Lynch Syndrome I

Cellular components related to Lynch Syndrome I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome GO:0005694 9.63 ZFR RAD51D MSH6 MSH2 MORC2 MLH1
2 MutLalpha complex GO:0032389 9.26 PMS2 MLH1
3 mismatch repair complex GO:0032300 9.02 PMS2 PMS1 MSH6 MSH2 MLH1
4 MutSalpha complex GO:0032301 8.96 MSH6 MSH2

Biological processes related to Lynch Syndrome I according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.85 RAD51D PMS2 PMS1 MSH6 MSH2 MLH1
2 cellular response to DNA damage stimulus GO:0006974 9.8 RAD51D PMS2 PMS1 MSH6 MSH2 MORC2
3 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 9.63 MSH6 MSH2 MLH1
4 determination of adult lifespan GO:0008340 9.55 MSH6 MSH2
5 negative regulation of DNA recombination GO:0045910 9.54 MSH6 MSH2
6 positive regulation of isotype switching to IgG isotypes GO:0048304 9.52 MSH2 MLH1
7 positive regulation of helicase activity GO:0051096 9.51 MSH6 MSH2
8 isotype switching GO:0045190 9.5 MSH6 MSH2 MLH1
9 positive regulation of isotype switching to IgA isotypes GO:0048298 9.49 MSH2 MLH1
10 maintenance of DNA repeat elements GO:0043570 9.48 MSH6 MSH2
11 protein deglutamylation GO:0035608 9.43 AGBL5 AGBL4
12 somatic recombination of immunoglobulin genes involved in immune response GO:0002204 9.4 MSH2 MLH1
13 somatic recombination of immunoglobulin gene segments GO:0016447 9.33 MSH6 MSH2 MLH1
14 somatic hypermutation of immunoglobulin genes GO:0016446 9.26 PMS2 MSH6 MSH2 MLH1
15 mismatch repair GO:0006298 9.02 PMS2 PMS1 MSH6 MSH2 MLH1

Molecular functions related to Lynch Syndrome I according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 10.1 RAD51D PMS2 PMS1 MSH6 MSH2 MORC2
2 zinc ion binding GO:0008270 10.02 ZFR PHC1 MORC2 CPZ AGBL5 AGBL4
3 chromatin binding GO:0003682 9.8 PHC1 MSH6 MSH2 MORC2 MLH1 DNAJC2
4 single-stranded DNA binding GO:0003697 9.71 RAD51D PMS2 MSH2 MLH1
5 carboxypeptidase activity GO:0004180 9.67 CPZ AGBL5 AGBL4
6 DNA-dependent ATPase activity GO:0008094 9.65 RAD51D MSH6 MSH2
7 ATPase activity GO:0016887 9.63 PMS2 PMS1 MSH6 MSH2 MORC2 MLH1
8 metallocarboxypeptidase activity GO:0004181 9.61 CPZ AGBL5 AGBL4
9 MutSalpha complex binding GO:0032407 9.54 PMS2 MLH1
10 MutLalpha complex binding GO:0032405 9.52 MSH6 MSH2
11 oxidized purine DNA binding GO:0032357 9.51 MSH6 MSH2
12 single guanine insertion binding GO:0032142 9.46 MSH6 MSH2
13 four-way junction DNA binding GO:0000400 9.43 RAD51D MSH6 MSH2
14 single thymine insertion binding GO:0032143 9.37 MSH6 MSH2
15 guanine/thymine mispair binding GO:0032137 9.13 MSH6 MSH2 MLH1
16 mismatched DNA binding GO:0030983 9.02 PMS2 PMS1 MSH6 MSH2 MLH1

Sources for Lynch Syndrome I

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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