MSH5 mutS homolog 5 [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

Location:: 6p21.33

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (31740005..31762676)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31593029..31615723)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31707782..31730453)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_21497-21498:1032976101:1 (e-PCR)
- UniSTS:268562

GDB:434012 (e-PCR)
- UniSTS:157204

D10S275 (e-PCR)
- UniSTS:147992

RH119364 (e-PCR)
- UniSTS:132904

L17705 (e-PCR)
- UniSTS:66091

D8S2279 (e-PCR)
- UniSTS:473907

RH103527 (e-PCR)
- UniSTS:97852

N3_2_1 (e-PCR)
- UniSTS:239174

GDB:314949 (e-PCR)
- UniSTS:156503

L18426 (e-PCR)
- UniSTS:34648

D10S16 (e-PCR)
- UniSTS:155756

D1S1423 (e-PCR)
- UniSTS:149619

L17877 (e-PCR)
- UniSTS:61334

D13S1568 (e-PCR)
- UniSTS:473497

L17809 (e-PCR)
- UniSTS:39087

L17971 (e-PCR)
- UniSTS:43966

D3S1673 (e-PCR)
- UniSTS:148450

D5S1597E (e-PCR)
- UniSTS:151019

D11S3316 (e-PCR)
- UniSTS:152558

Readthrough MSH5-SAPCD1

Readthrough gene: MSH5-SAPCD1, Included gene: SAPCD1

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

NG_011611.1 RefSeqGene

Range

5009..27680

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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]
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]