MSH4 mutS homolog 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MSH4provided by HGNC
Official Full Name: mutS homolog 4provided by HGNC
Primary source: HGNC:HGNC:7327
See related: Ensembl:ENSG00000057468 MIM:602105; AllianceGenome:HGNC:7327
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: ASG; POF20; SPGF2
Summary: This gene encodes a member of the DNA mismatch repair mutS family. This member is a meiosis-specific protein that is not involved in DNA mismatch correction, but is required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis I. This protein and MSH5 form a heterodimer which binds uniquely to a Holliday Junction and its developmental progenitor, thus provoking ADP-ATP exchange, and stabilizing the interaction between parental chromosomes during meiosis double-stranded break repair. [provided by RefSeq, Aug 2011]
Expression: Biased expression in testis (RPKM 2.6) and small intestine (RPKM 0.1) See more
Orthologs: mouse all
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Genomic context

Location:: 1p31.1

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (75796882..75913242)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (75633544..75751219)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (76262567..76378927)

Chromosome 1 - NC_000001.11 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?

A novel homozygote nonsense variant of MSH4 leads to primary ovarian insufficiency and non-obstructive azoospermia.
Title: A novel homozygote nonsense variant of MSH4 leads to primary ovarian insufficiency and non-obstructive azoospermia.
Identification of compound heterozygous variants in MSH4 as a novel genetic cause of diminished ovarian reserve.
Title: Identification of compound heterozygous variants in MSH4 as a novel genetic cause of diminished ovarian reserve.
Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia.
Title: Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia.
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.
Semiquantitative promoter methylation of MLH1 and MSH2 genes and their impact on sperm DNA fragmentation and chromatin condensation in infertile men.
Title: Semiquantitative promoter methylation of MLH1 and MSH2 genes and their impact on sperm DNA fragmentation and chromatin condensation in infertile men.
Rare missense variant in MSH4 associated with primary gonadal failure in both 46, XX and 46, XY individuals.
Title: Rare missense variant in MSH4 associated with primary gonadal failure in both 46, XX and 46, XY individuals.
Study describes the first MSH4 mutation associated with POI and increases the number of meiotic/DNA repair genes formally implicated as being responsible for this condition.
Title: A homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiency.
inactivation of MSH4 in germ cells may have played a role in the acquisition of additional TP53 and LATS1 germline mutations in a Li-Fraumeni family
Title: TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors.
hMSH4 interacts with HDAC3.
Title: DNA damage induced MutS homologue hMSH4 acetylation.
Our current study has revealed a role for hMSH4 in the maintenance of genomic stability by suppressing NHEJ-mediated DSB repair.
Title: MutS homologue hMSH4: interaction with eIF3f and a role in NHEJ-mediated DSB repair.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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 20 MedGen: C5677011 OMIM: 619938 GeneReviews: Not available	not available
Spermatogenic failure 2 MedGen: C1862459 OMIM: 108420 GeneReviews: Not available	not available

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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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 DNA binding	TAS Traceable Author Statement more info	PubMed
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 female gamete generation	IEA Inferred from Electronic Annotation more info
involved_in homologous chromosome pairing at meiosis	IEA Inferred from Electronic Annotation more info
involved_in mismatch repair	IEA Inferred from Electronic Annotation more info
involved_in ovarian follicle development	IEA Inferred from Electronic Annotation more info
involved_in reciprocal meiotic recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromosome	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in recombination nodule	IEA Inferred from Electronic Annotation more info
located_in synaptonemal complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: mutS protein homolog 4

Names: hMSH4

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_029861.1 RefSeqGene

Range

5012..121372

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002440.4 → NP_002431.2 mutS protein homolog 4

See identical proteins and their annotated locations for NP_002431.2

Status: REVIEWED

Source sequence(s)

AF104243, AL445464, BC033030, DB077677

Consensus CDS

CCDS670.1

UniProtKB/Swiss-Prot

O15457, Q5T4U6, Q8NEB3, Q9UNP8

Related

ENSP00000263187.3, ENST00000263187.4

Conserved Domains (5) summary

smart00533
Location:334 → 656

MUTSd; DNA-binding domain of DNA mismatch repair MUTS family

pfam00488
Location:635 → 871

MutS_V; MutS domain V

pfam05188
Location:156 → 293

MutS_II; MutS domain II

pfam05190
Location:493 → 587

MutS_IV; MutS family domain IV

pfam05192
Location:315 → 400

MutS_III; MutS domain III