MSH2 mutS homolog 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MSH2provided by HGNC
Official Full Name: mutS homolog 2provided by HGNC
Primary source: HGNC:HGNC:7325
See related: Ensembl:ENSG00000095002 MIM:609309
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FCC1; COCA1; HNPCC; LCFS2; hMSH2; HNPCC1
Summary: This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Expression: Ubiquitous expression in lymph node (RPKM 3.7), testis (RPKM 3.4) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2p21-p16.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (47403067..47634501)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (47630206..47739716)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dynamic human MutSalpha-MutLalpha complexes compact mismatched DNA.
Title: Dynamic human MutSα-MutLα complexes compact mismatched DNA.
SMARCAD1-mediated recruitment of the DNA mismatch repair protein MutLalpha to MutSalpha on damaged chromatin induces apoptosis in human cells.
Title: SMARCAD1-mediated recruitment of the DNA mismatch repair protein MutLα to MutSα on damaged chromatin induces apoptosis in human cells.
Study demonstrated that MSH2 low expression due to hypermethylation may play an important role in platinum resistance in epithelial ovarian cancer EOC and the expression profile of MSH2 could be a potential biomarker for EOC prognosis.
Title: Hypermethylation of mismatch repair gene hMSH2 associates with platinum-resistant disease in epithelial ovarian cancer.
Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed colorectal adenomas in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6. Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2. None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC.
Title: Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome.
Novel pathogenic MSH2 mutation and new DNA repair genes variants in a Tunisian Lynch syndrome family with discordant twins.
Title: Identification of novel pathogenic MSH2 mutation and new DNA repair genes variants: investigation of a Tunisian Lynch syndrome family with discordant twins.
loss of expression in 23/48 premenopausal breast cancer cases and 14/32 postmenopausal cases
Title: Expressional analysis of MLH1 and MSH2 in breast cancer.
There is a coexpression between the hMSH2, hMSH6 and NF-kB genes in oral squamous cell carcinomas.
Title: Expression of MMR system genes is correlated to NF-kB in patients with oral squamous cell carcinoma.
The MSH2 c.1022T>C variant is a pathogenic founder variation associated with a high risk of cancer.
Title: MSH2 c.1022T>C, p.Leu341Pro is a founder pathogenic variation and a major cause of Lynch syndrome in the North of France.
The genotype and allele frequencies of the rs2303428 and rs1800734 polymorphisms were not significantly different between the case and control groups. Compared with wild homozygous genotype, the presence of variant alleles (heterozygous and variant homozygous genotypes) did not affect the risk of developing epithelial ovarian cancer.
Title: Genetic polymorphisms in <i>hMSH2</i> and <i>hMLH1</i> genes are associated with prognosis in epithelial ovarian cancer patients.
Results found that Msh2 deficiency results in genome-wide changes in histone H3 methylation profiles preceding intestinal tumor development.
Title: Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine.

Submit: New GeneRIF Correction See all GeneRIFs (486)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in MSH2 that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Lynch syndrome I MedGen: C2936783 OMIM: 120435 GeneReviews: Lynch Syndrome	Compare labs
Muir-Torre syndrome MedGen: C1321489 OMIM: 158320 GeneReviews: Lynch Syndrome	Compare labs
Turcot syndrome MedGen: C0265325 OMIM: 276300 GeneReviews: Lynch Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2015-07-09) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2015-07-09) ClinGen Genome Curation PagePubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
retropepsin	gag-pol	HIV-1 PR is identified to have a physical interaction with mutS homolog 2, colon cancer, nonpolyposis type 1 (MSH2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

G65627 (e-PCR)
- UniSTS:225564

RH93469 (e-PCR)
- UniSTS:91508

GDB:599286 (e-PCR)
- UniSTS:158114

GDB:599300 (e-PCR)
- UniSTS:158118

GDB:549135 (e-PCR)
- UniSTS:157610

GDB:599318 (e-PCR)
- UniSTS:158122

GDB:599321 (e-PCR)
- UniSTS:158123

WI-18791 (e-PCR)
- UniSTS:28587

GDB:599324 (e-PCR)
- UniSTS:158124

GDB:599327 (e-PCR)
- UniSTS:158125

GDB:599341 (e-PCR)
- UniSTS:158128

GDB:599344 (e-PCR)
- UniSTS:158129

GDB:599347 (e-PCR)
- UniSTS:158130

GDB:599356 (e-PCR)
- UniSTS:158131

GDB:599360 (e-PCR)
- UniSTS:158132

GDB:599364 (e-PCR)
- UniSTS:158133

GDB:599367 (e-PCR)
- UniSTS:158134

GDB:599372 (e-PCR)
- UniSTS:158135

GDB:599380 (e-PCR)
- UniSTS:158137

RH70533 (e-PCR)
- UniSTS:52163

D2S2563 (e-PCR)
- UniSTS:27108

SHGC-2762 (e-PCR)
- UniSTS:30458

Homology

Homologs of the MSH2 gene: The MSH2 gene is conserved in dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, and frog.
Orthologs from Annotation Pipeline: 332 organisms have orthologs with human gene MSH2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to ADP binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to ATP binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to ATPase activity	IDA Inferred from Direct Assay more info	PubMed
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA-dependent ATPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to MutLalpha complex binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to MutLalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
centromeric DNA binding	IEA Inferred from Electronic Annotation more info
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to dinucleotide insertion or deletion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to dinucleotide repeat insertion binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to dinucleotide repeat insertion binding	IDA Inferred from Direct Assay more info	PubMed
double-strand/single-strand DNA junction binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to four-way junction DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to four-way junction DNA binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to guanine/thymine mispair binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to guanine/thymine mispair binding	IDA Inferred from Direct Assay more info	PubMed
guanine/thymine mispair binding	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to mismatched DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to mismatched DNA binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to oxidized purine DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to oxidized purine DNA binding	IDA Inferred from Direct Assay more info	PubMed
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to single guanine insertion binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to single guanine insertion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to single thymine insertion binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to single thymine insertion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
B cell mediated immunity	ISS Inferred from Sequence or Structural Similarity more info
DNA recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA repair	IDA Inferred from Direct Assay more info	PubMed
cell cycle arrest	IEA Inferred from Electronic Annotation more info
determination of adult lifespan	IEA Inferred from Electronic Annotation more info
double-strand break repair	IEA Inferred from Electronic Annotation more info
germ cell development	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
intra-S DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IBA Inferred from Biological aspect of Ancestor more info	PubMed
isotype switching	ISS Inferred from Sequence or Structural Similarity more info
maintenance of DNA repeat elements	IBA Inferred from Biological aspect of Ancestor more info	PubMed
maintenance of DNA repeat elements	IMP Inferred from Mutant Phenotype more info	PubMed
male gonad development	ISS Inferred from Sequence or Structural Similarity more info
mismatch repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mismatch repair	IDA Inferred from Direct Assay more info	PubMed
mismatch repair	IGI Inferred from Genetic Interaction more info	PubMed
mismatch repair	TAS Traceable Author Statement more info
negative regulation of DNA recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of DNA recombination	IDA Inferred from Direct Assay more info	PubMed
negative regulation of DNA recombination	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
oxidative phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of helicase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of isotype switching to IgA isotypes	IEA Inferred from Electronic Annotation more info
positive regulation of isotype switching to IgG isotypes	IEA Inferred from Electronic Annotation more info
postreplication repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
postreplication repair	IDA Inferred from Direct Assay more info	PubMed
protein localization to chromatin	IMP Inferred from Mutant Phenotype more info	PubMed
response to UV-B	ISS Inferred from Sequence or Structural Similarity more info
response to X-ray	ISS Inferred from Sequence or Structural Similarity more info
somatic hypermutation of immunoglobulin genes	IEA Inferred from Electronic Annotation more info
somatic recombination of immunoglobulin gene segments	ISS Inferred from Sequence or Structural Similarity more info
somatic recombination of immunoglobulin genes involved in immune response	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
MutSalpha complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
MutSalpha complex	IDA Inferred from Direct Assay more info	PubMed
MutSbeta complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
MutSbeta complex	IDA Inferred from Direct Assay more info	PubMed
membrane	HDA more info	PubMed
mismatch repair complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nuclear chromosome, telomeric region	HDA more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: DNA mismatch repair protein Msh2

Names: DNA mismatch repair protein Msh2 transcript; mutS homolog 2, colon cancer, nonpolyposis type 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007110.2 RefSeqGene

Range

4944..85105

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_218

mRNA and Protein(s)

NM_000251.3 → NP_000242.1 DNA mismatch repair protein Msh2 isoform 1

See identical proteins and their annotated locations for NP_000242.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK304496, CB250419, U04045

Consensus CDS

CCDS1834.1

UniProtKB/Swiss-Prot

P43246

Related

ENSP00000233146.2, ENST00000233146.7

Conserved Domains (1) summary

COG0249
Location:23 → 853

MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
NM_001258281.1 → NP_001245210.1 DNA mismatch repair protein Msh2 isoform 2

See identical proteins and their annotated locations for NP_001245210.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate segment of the first exon, including the translation start site, compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AK304496, CB250419, DC342099

Consensus CDS

CCDS58709.1

UniProtKB/Swiss-Prot

P43246

Related

ENSP00000442697.1, ENST00000543555.6

Conserved Domains (2) summary

COG0249
Location:58 → 787

MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

pfam01624
Location:5 → 66

MutS_I; MutS domain I

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 Primary Assembly

Range

47403067..47634501

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011532867.2 → XP_011531169.1 DNA mismatch repair protein Msh2 isoform X2

See identical proteins and their annotated locations for XP_011531169.1

Related

ENSP00000495455.1, ENST00000645506.1

Conserved Domains (6) summary

cd03285
Location:633 → 852

ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog

COG0249
Location:23 → 853

MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

pfam01624
Location:18 → 132

MutS_I; MutS domain I

pfam05188
Location:158 → 284

MutS_II; MutS domain II

pfam05190
Location:473 → 569

MutS_IV; MutS family domain IV

pfam05192
Location:305 → 423

MutS_III; MutS domain III
XM_005264332.4 → XP_005264389.2 DNA mismatch repair protein Msh2 isoform X1

Conserved Domains (6) summary

cd03285
Location:633 → 852

ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog

COG0249
Location:23 → 853

MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

pfam01624
Location:18 → 132

MutS_I; MutS domain I

pfam05188
Location:158 → 284

MutS_II; MutS domain II

pfam05190
Location:473 → 569

MutS_IV; MutS family domain IV

pfam05192
Location:305 → 423

MutS_III; MutS domain III