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MSH5 mutS homolog 5 [ Homo sapiens (human) ]

Gene ID: 4439, updated on 5-Mar-2024

Summary

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Official Symbol
MSH5provided by HGNC
Official Full Name
mutS homolog 5provided by HGNC
Primary source
HGNC:HGNC:7328
See related
Ensembl:ENSG00000204410 MIM:603382; AllianceGenome:HGNC:7328
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
G7; NG23; POF13; MUTSH5; SPGF74
Summary
This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene. [provided by RefSeq, Feb 2011]
Expression
Broad expression in testis (RPKM 8.9), bone marrow (RPKM 7.5) and 23 other tissues See more
Orthologs
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Genomic context

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Location:
6p21.33
Exon count:
25
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (31740005..31762676)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (31593029..31615723)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31707782..31730453)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene DDAH family member 2, ADMA-independent Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:31701615-31702814 Neighboring gene chloride intracellular channel 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31704508-31705382 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31707224-31707854 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31707855-31708486 Neighboring gene MSH5-SAPCD1 readthrough (NMD candidate) Neighboring gene RNA, U6 small nuclear 850, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31731027-31731582 Neighboring gene SAPCD1 antisense RNA 1 Neighboring gene suppressor APC domain containing 1 Neighboring gene von Willebrand factor A domain containing 7 Neighboring gene Sharpr-MPRA regulatory regions 3149 and 4553

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. A Homozygous Loss-of-Function Mutation in MSH5 Abolishes MutSγ Axial Loading and Causes Meiotic Arrest in NOA-Affected Individuals. Gong C, et al. Int J Mol Sci, 2022 Jun 10. PMID 35742973, Free PMC Article
  2. Association of hMSH5 C85T polymorphism with radiation sensitivity of testicular cell lines GC-1, GC-2, TM3, and TM4. Lin M, et al. Andrology, 2020 Sep. PMID 32306546
  3. MutS homologue hMSH5: recombinational DSB repair and non-synonymous polymorphic variants. Wu X, et al. PLoS One, 2013. PMID 24023853, Free PMC Article
  4. The human MSH5 (MutSHomolog 5) protein localizes to mitochondria and protects the mitochondrial genome from oxidative damage. Bannwarth S, et al. Mitochondrion, 2012 Nov. PMID 22917773
  5. hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization. Lahaye F, et al. Nucleic Acids Res, 2010 Jun. PMID 20185565, Free PMC Article

See all (62) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A Homozygous Loss-of-Function Mutation in MSH5 Abolishes MutSgamma Axial Loading and Causes Meiotic Arrest in NOA-Affected Individuals.
    Title: A Homozygous Loss-of-Function Mutation in MSH5 Abolishes MutSγ Axial Loading and Causes Meiotic Arrest in NOA-Affected Individuals.
  2. Mutations of MSH5 in nonobstructive azoospermia (NOA) and rescued via in vivo gene editing.
    Title: Mutations of MSH5 in nonobstructive azoospermia (NOA) and rescued via in vivo gene editing.
  3. Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes.
    Title: Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes.
  4. Association of hMSH5 C85T polymorphism with radiation sensitivity of testicular cell lines GC-1, GC-2, TM3, and TM4.
    Title: Association of hMSH5 C85T polymorphism with radiation sensitivity of testicular cell lines GC-1, GC-2, TM3, and TM4.
  5. Decreased expression of HCP5 in biochemical premature ovarian insufficiency (bPOI) contributed to dysfunctional granulosa cells by regulating MSH5 transcription and DNA damage repair via the interaction with YB1, providing a novel epigenetic mechanism for POI pathogenesis.
    Title: Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1.
  6. Findings indicate that carriers of the MSH5 rs707939 T allele, the MSH2 rs6544991 C allele, the MSH3 rs6151627 and rs6151670 G alleles, and the MSH3 rs7709909 T allele have poor toxicity tolerance to platinum-based chemotherapy in non-small cell lung cancer patients.
    Title: Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients.
  7. From sanger sequencing of MSH5 in 200 sporadic POI patients, we identified three heterozygous mutations . Considering the heterozygous p.D487Y carrier in the POI pedigree was fertile, the causality of the three heterozygous mutations in POI need more evidence
    Title: Mutations in MSH5 in primary ovarian insufficiency.
  8. our data point to the existence of a functional interplay between hMSH5 and FANCJ in double-strand break repair induced by replication stress.
    Title: hMSH5 Facilitates the Repair of Camptothecin-induced Double-strand Breaks through an Interaction with FANCJ.
  9. the roles of hMSH5 variants in the processes of DNA damage response and repair
    Title: MutS homologue hMSH5: recombinational DSB repair and non-synonymous polymorphic variants.
  10. Authors show that MSH5 (MutSHomolog 5) is localized into the mitochondria of germ and somatic cells.
    Title: The human MSH5 (MutSHomolog 5) protein localizes to mitochondria and protects the mitochondrial genome from oxidative damage.
Submit: New GeneRIF Correction See all GeneRIFs (28)

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
Premature ovarian failure 13
MedGen: C4479510 OMIM: 617442 GeneReviews: Not available
Compare labs
Spermatogenic failure 74
MedGen: C5677010 OMIM: 619937 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Common 5p15.33 and 6p21.33 variants influence lung cancer risk.
EBI GWAS Catalog
Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis.
EBI GWAS Catalog
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.
EBI GWAS Catalog

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

Readthrough MSH5-SAPCD1

Readthrough gene: MSH5-SAPCD1, Included gene: SAPCD1

Homology

Clone Names

  • MGC2939, DKFZp434C1615

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
  
enables double-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables mismatched DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in chiasma assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mismatch repair IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
mutS protein homolog 5

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_011611.1 RefSeqGene

    Range
    5009..27680
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002441.5 → NP_002432.1  mutS protein homolog 5 isoform c

    See identical proteins and their annotated locations for NP_002432.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (c) that is longer than isoform a. Both variants 3 and 4 encode the same isoform.
    Source sequence(s)
    AF048986, AL662899, DB448226
    Consensus CDS
    CCDS4720.1
    UniProtKB/Swiss-Prot
    B0V033, B0V034, O43196, O60586, Q5BLU9, Q5SSR1, Q8IW44, Q9BQC7
    UniProtKB/TrEMBL
    A0A024RCM1, A0A1U9X825, A0A1U9X828
    Related
    ENSP00000364908.3, ENST00000375755.8
    Conserved Domains (2) summary
    cd03281
    Location:557 → 763
    ABC_MSH5_euk; ATP-binding cassette domain of eukaryotic MutS5 homolog
    COG0249
    Location:129 → 813
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

  2. NM_025259.6 → NP_079535.4  mutS protein homolog 5 isoform a

    See identical proteins and their annotated locations for NP_079535.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shortest transcript and encodes the shortest isoform (a).
    Source sequence(s)
    BC041031, DB448226
    Consensus CDS
    CCDS34409.2
    UniProtKB/TrEMBL
    A0A0G2JK88
    Related
    ENSP00000364892.3, ENST00000375740.7
    Conserved Domains (2) summary
    cd03281
    Location:574 → 762
    ABC_MSH5_euk; ATP-binding cassette domain of eukaryotic MutS5 homolog
    COG0249
    Location:194 → 762
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

  3. NM_172165.4 → NP_751897.1  mutS protein homolog 5 isoform b

    See identical proteins and their annotated locations for NP_751897.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (b) that is longer than isoform a.
    Source sequence(s)
    BC001358, DB448226
    Consensus CDS
    CCDS34410.1
    UniProtKB/TrEMBL
    A0A1U9X825, A0A1U9X828
    Related
    ENSP00000364855.3, ENST00000375703.7
    Conserved Domains (2) summary
    cd03281
    Location:557 → 764
    ABC_MSH5_euk; ATP-binding cassette domain of eukaryotic MutS5 homolog
    COG0249
    Location:129 → 814
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

  4. NM_172166.4 → NP_751898.1  mutS protein homolog 5 isoform c

    See identical proteins and their annotated locations for NP_751898.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (c) that is longer than isoform a. Both variants 3 and 4 encode the same isoform.
    Source sequence(s)
    AF034759, BF116106, DB448226
    Consensus CDS
    CCDS4720.1
    UniProtKB/Swiss-Prot
    B0V033, B0V034, O43196, O60586, Q5BLU9, Q5SSR1, Q8IW44, Q9BQC7
    UniProtKB/TrEMBL
    A0A024RCM1, A0A1U9X825, A0A1U9X828
    Related
    ENSP00000364903.3, ENST00000375750.9
    Conserved Domains (2) summary
    cd03281
    Location:557 → 763
    ABC_MSH5_euk; ATP-binding cassette domain of eukaryotic MutS5 homolog
    COG0249
    Location:129 → 813
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

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_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    31740005..31762676
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NT_167244.2 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    3090764..3095288
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

    Range
    3217285..3239933
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

    Range
    2987771..3010450
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

    Range
    3045052..3052474
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

    Range
    3081881..3104565
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

    Range
    2995824..3017449
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

    Range
    3039302..3061968
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    31593029..31615723
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43196.1 GenPept UniProtKB/Swiss-Prot:O43196

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