Gene: EPM2AIP1

Alternate names for this Gene: -

Gene Summary: The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless.

Gene is located in Chromosome: 3

Location in Chromosome : 3p22.2

Description of this Gene: EPM2A interacting protein 1

Type of Gene: protein-coding

Gene: MLH1

Alternate names for this Gene: COCA2|FCC2|HNPCC|HNPCC2|MMRCS1|hMLH1

Gene Summary: The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC).

Gene is located in Chromosome: 3

Location in Chromosome : 3p22.2

Description of this Gene: mutL homolog 1

Type of Gene: protein-coding

rs267607706 in EPM2AIP1;MLH1 gene and Hereditary Non-Polyposis Colon Cancer Type 2 PMID 9559627 1998 Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer.

PMID 9326924 1997 A human compound heterozygote for two MLH1 missense mutations.

PMID 9833759 1998 Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer.

PMID 8872463 1996 Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer.

PMID 22753075 2012 Functional characterization of MLH1 missense variants identified in Lynch syndrome patients.

PMID 20020535 2010 A cell-free assay for the functional analysis of variants of the mismatch repair protein MLH1.

PMID 8993976 1997 Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer.

PMID 8797773 1996 Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer.

PMID 9311737 1997 Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations.

PMID 11726306 2001 Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?

PMID 8571956 1996 Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16.

PMID 10375096 1999 Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer.

PMID 11781295 2002 Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system.

PMID 10598809 1999 Missense mutations in hMLH1 associated with colorectal cancer.

PMID 11839723 2002 Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing.

PMID 10413423 1999 Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer.

PMID 10627141 1998 Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability. Mutations in brief no. 157. Online.

PMID 15365995 2004 Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families.

PMID 11793442 2002 Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer.

PMID 11748856 2001 Eight novel germline MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer families from Spain.

rs41285097 in EPM2AIP1;MLH1 gene and Hereditary Nonpolyposis Colorectal Cancer PMID 12919137 2003 Germline hMLH1 promoter mutation in a Newfoundland HNPCC kindred.

PMID 15849733 2005 Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.

PMID 12537657 2002 An intronic polymorphism of the hMLH1 gene contributes toward incomplete genetic testing for HNPCC.

PMID 18383312 2008 Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR).

PMID 20864636 2010 A novel and rapid method of determining the effect of unclassified MLH1 genetic variants on differential allelic expression.

PMID 12362047 2002 Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States.

PMID 22949387 2013 Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions.

PMID 23741719 2013 Development of a new, simple and cost-effective diagnostic tool for genetic screening of hereditary colorectal cancer--the DNA microarray assay.

PMID 21404117 2011 Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies.

PMID 17594722 2007 Functional analysis helps to clarify the clinical importance of unclassified variants in DNA mismatch repair genes.

PMID 10323887 1999 Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer.

PMID 17510385 2007 Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays.

PMID 18373977 2008 The interplay between hMLH1 and hMRE11: role in MMR and the effect of hMLH1 mutations.

PMID 16083711 2005 Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1.

PMID 11948175 2002 Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalpha.

PMID 12810663 2003 A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations.

PMID 25420488 2015 Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India.

rs267607709 in EPM2AIP1;MLH1 gene and Hereditary Nonpolyposis Colorectal Neoplasms PMID 24362816 2014 Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

PMID 15713769 2005 Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.

PMID 19267393 2009 Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics.

PMID 22949379 2013 A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.

PMID 15475387 2004 Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain.

PMID 12373605 2002 Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach.

PMID 23403630 2013 Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis.

PMID 20704743 2010 A novel pathogenic MLH1 missense mutation, c.112A > C, p.Asn38His, in six families with Lynch syndrome.

PMID 20020535 2010 A cell-free assay for the functional analysis of variants of the mismatch repair protein MLH1.

PMID 26895986 2016 Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort.

PMID 11112663 2001 Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds.

PMID 24302565 2015 Consequences of germline variation disrupting the constitutional translational initiation codon start sites of MLH1 and BRCA2: Use of potential alternative start sites and implications for predicting variant pathogenicity.

PMID 22878509 2013 Identification of constitutional MLH1 epimutations and promoter variants in colorectal cancer patients from the Colon Cancer Family Registry.

PMID 29790873 2018 Diversity of genetic events associated with MLH1 promoter methylation in Lynch syndrome families with heritable constitutional epimutation.

rs63751012 in EPM2AIP1;MLH1 gene and Malignant tumor of colon PMID 25420488 2015 Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India.

rs63750648 in EPM2AIP1;MLH1 gene and Neoplastic Syndromes, Hereditary PMID 12362047 2002 Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States.

PMID 20864636 2010 A novel and rapid method of determining the effect of unclassified MLH1 genetic variants on differential allelic expression.

PMID 12537657 2002 An intronic polymorphism of the hMLH1 gene contributes toward incomplete genetic testing for HNPCC.

PMID 15475387 2004 Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain.

PMID 25980754 2015 Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

PMID 21404117 2011 Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies.

PMID 10323887 1999 Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer.

PMID 9298827 1997 Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes.

PMID 12810663 2003 A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations.

PMID 22753075 2012 Functional characterization of MLH1 missense variants identified in Lynch syndrome patients.

PMID 17510385 2007 Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays.

PMID 16736289 2006 Germline mutations of the hMLH1 and hMSH2 mismatch repair genes in Belgian hereditary nonpolyposis colon cancer (HNPCC) patients.

PMID 16216036 2005 Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining.

PMID 16083711 2005 Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1.

PMID 25420488 2015 Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India.

PMID 16807412 2006 Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer.

PMID 25430799 2015 Genetic features of Lynch syndrome in the Israeli population.

rs63751012 in EPM2AIP1;MLH1 gene and Polyp of large intestine PMID 25420488 2015 Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India.

rs121912965 in EPM2AIP1;MLH1 gene and Turcot syndrome (disorder) PMID 22167527 2012 Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline.

PMID 15604628 2004 Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

PMID 25452455 2015 Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines.

PMID 11427529 2001 The interaction of DNA mismatch repair proteins with human exonuclease I.

PMID 25394175 2015 A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

PMID 7661930 1995 The molecular basis of Turcot's syndrome.

PMID 17440981 2007 Biallelic germline mutations of mismatch-repair genes: a possible cause for multiple pediatric malignancies.