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    MSH3 mutS homolog 3 [ Homo sapiens (human) ]

    Gene ID: 4437, updated on 7-Apr-2024

    Summary

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    Official Symbol
    MSH3provided by HGNC
    Official Full Name
    mutS homolog 3provided by HGNC
    Primary source
    HGNC:HGNC:7326
    See related
    Ensembl:ENSG00000113318 MIM:600887; AllianceGenome:HGNC:7326
    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
    DUP; FAP4; MRP1
    Summary
    The protein encoded by this gene forms a heterodimer with MSH2 to form MutS beta, part of the post-replicative DNA mismatch repair system. MutS beta initiates mismatch repair by binding to a mismatch and then forming a complex with MutL alpha heterodimer. This gene contains a polymorphic 9 bp tandem repeat sequence in the first exon. The repeat is present 6 times in the reference genome sequence and 3-7 repeats have been reported. Defects in this gene are a cause of susceptibility to endometrial cancer. [provided by RefSeq, Mar 2011]
    Expression
    Ubiquitous expression in fat (RPKM 8.1), kidney (RPKM 7.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    5q14.1
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (80654652..80876815)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (81139552..81361456)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (79950471..80172634)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 2279 Neighboring gene long intergenic non-protein coding RNA 1337 Neighboring gene Sharpr-MPRA regulatory regions 13584 and 3862 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:79950324-79951092 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:79963410-79963977 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:79963978-79964546 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:79968379-79969578 Neighboring gene MPRA-validated peak5310 silencer Neighboring gene MT-RNR2 like 2 (pseudogene) Neighboring gene dihydrofolate reductase Neighboring gene ReSE screen-validated silencer GRCh37_chr5:80040756-80040944 Neighboring gene S-phase kinase-associated protein 1-like Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:80043670-80044230 Neighboring gene MPRA-validated peak5311 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22728 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:80142431-80142931 Neighboring gene uncharacterized LOC107986428 Neighboring gene ribosomal protein S26 pseudogene 27 Neighboring gene RASGRF2 antisense RNA 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:80252674-80253194 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:80256285-80257006 Neighboring gene Ras protein specific guanine nucleotide releasing factor 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. A large family with MSH3-related polyposis. Aelvoet AS, et al. Fam Cancer, 2023 Jan. PMID 35675019, Free PMC Article
    2. The Human DNA Mismatch Repair Protein MSH3 Contains Nuclear Localization and Export Signals That Enable Nuclear-Cytosolic Shuttling in Response to Inflammation. Tseng-Rogenski SS, et al. Mol Cell Biol, 2020 Jun 15. PMID 32284349, Free PMC Article
    3. Inflammation-Associated Microsatellite Alterations Caused by MSH3 Dysfunction Are Prevalent in Ulcerative Colitis and Increase With Neoplastic Advancement. Munakata K, et al. Clin Transl Gastroenterol, 2019 Dec. PMID 31789935, Free PMC Article
    4. EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer. Mohammadpour S, et al. J Cell Physiol, 2020 Apr. PMID 31549400
    5. MutSβ abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions. Keogh N, et al. Nucleic Acids Res, 2017 Sep 29. PMID 28973443, Free PMC Article

    See all (176) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer.
      Title: High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer.
    2. MSH3: a confirmed predisposing gene for adenomatous polyposis.
      Title: MSH3: a confirmed predisposing gene for adenomatous polyposis.
    3. Novel insights into the ecDNA formation mechanism involving MSH3 in methotrexate-resistant human colorectal cancer cells.
      Title: Novel insights into the ecDNA formation mechanism involving MSH3 in methotrexate‑resistant human colorectal cancer cells.
    4. MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1.
      Title: MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1.
    5. A large family with MSH3-related polyposis.
      Title: A large family with MSH3-related polyposis.
    6. Prevalence and Characterization of Biallelic and Monoallelic NTHL1 and MSH3 Variant Carriers From a Pan-Cancer Patient Population.
      Title: Prevalence and Characterization of Biallelic and Monoallelic NTHL1 and MSH3 Variant Carriers From a Pan-Cancer Patient Population.
    7. Coordinated roles of SLX4 and MutSbeta in DNA repair and the maintenance of genome stability.
      Title: Coordinated roles of SLX4 and MutSβ in DNA repair and the maintenance of genome stability.
    8. EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer.
      Title: EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer.
    9. Genetic Polymorphism of Mismatch Repair Genes and Susceptibility to Prostate Cancer.
      Title: Genetic Polymorphism of Mismatch Repair Genes and Susceptibility to Prostate Cancer.
    10. Inflammation-Associated Microsatellite Alterations Caused by MSH3 Dysfunction Are Prevalent in Ulcerative Colitis and Increase With Neoplastic Advancement.
      Title: Inflammation-Associated Microsatellite Alterations Caused by MSH3 Dysfunction Are Prevalent in Ulcerative Colitis and Increase With Neoplastic Advancement.
    Submit: New GeneRIF Correction See all GeneRIFs (68)

    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

    Associated conditions

    Description Tests
    Endometrial carcinoma
    MedGen: C0476089 OMIM: 608089 GeneReviews: Not available
    		Compare labs
    Familial adenomatous polyposis 4
    MedGen: C4310719 OMIM: 617100 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC163306, MGC163308

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP-dependent DNA damage sensor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    contributes_to dinucleotide insertion or deletion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to dinucleotide repeat insertion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables double-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    NOT enables guanine/thymine mispair binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to mismatched DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT contributes_to oxidized purine DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    NOT enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to single guanine 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
    involved_in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in maintenance of DNA repeat elements IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mismatch repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mismatch repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mismatch repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitotic recombination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of DNA recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of helicase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in somatic recombination of immunoglobulin gene segments IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of MutSbeta complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of MutSbeta complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    DNA mismatch repair protein Msh3
    Names
    divergent upstream protein
    epididymis secretory sperm binding protein
    hMSH3
    mismatch repair protein 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

    1. NG_016607.2 RefSeqGene

      Range
      5178..227341
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002439.5 → NP_002430.3  DNA mismatch repair protein Msh3

      See identical proteins and their annotated locations for NP_002430.3

      Status: REVIEWED

      Source sequence(s)
      AA601983, AC022493, BC130434, J04810, U61981
      Consensus CDS
      CCDS34195.1
      UniProtKB/Swiss-Prot
      A1L480, A1L482, A6NMM6, P20585, Q6PJT5, Q86UQ6, Q92867
      UniProtKB/TrEMBL
      A0A384MDZ1
      Related
      ENSP00000265081.6, ENST00000265081.7
      Conserved Domains (6) summary
      COG0249
      Location:225 → 1111
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam00488
      Location:846 → 1094
      MutS_V; MutS domain V
      pfam01624
      Location:230 → 343
      MutS_I; MutS domain I
      pfam05188
      Location:366 → 523
      MutS_II; MutS domain II
      pfam05192
      Location:540 → 680
      MutS_III; MutS domain III
      cl17822
      Location:717 → 783
      MutS_III; MutS domain III

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      80654652..80876815
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      81139552..81361456
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P20585.4 GenPept UniProtKB/Swiss-Prot:P20585

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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