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; MMRCS2
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
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Genomic context

Location:: 2p21-p16.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (47403067..47634501)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (47630206..47710367)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics.
Title: Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics.
DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers.
Title: DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers.
DNMT1 promotes cell proliferation via methylating hMLH1 and hMSH2 promoters in EGFR-mutated non-small cell lung cancer.
Title: DNMT1 promotes cell proliferation via methylating hMLH1 and hMSH2 promoters in EGFR-mutated non-small cell lung cancer.
Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.
Title: Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.
MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes.
Title: MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes.
High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers.
Title: High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers.
Correlation of MSH2 exonic deletions and protein downregulation with breast cancer biomarkers and outcome in Pakistani women/patients.
Title: Correlation of MSH2 exonic deletions and protein downregulation with breast cancer biomarkers and outcome in Pakistani women/patients.
Structural debilitation of mutation G322D associated with MSH2 and their role in triple negative breast cancer.
Title: Structural debilitation of mutation G322D associated with MSH2 and their role in triple negative breast cancer.
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.

Submit: New GeneRIF Correction See all GeneRIFs (494)

Phenotypes

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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
MISMATCH REPAIR CANCER SYNDROME 2 MedGen: CN293538 OMIM: 619096 GeneReviews: Not available	Compare labs
Muir-Torre syndrome MedGen: C1321489 OMIM: 158320 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

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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: 352 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
chromosome, telomeric region	HDA more info	PubMed
membrane	HDA more info	PubMed
mismatch repair complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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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)

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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 109.20210226

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