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 progeni... See more...

Aliases for MSH4 Gene

Aliases for MSH4 Gene

  • MutS Homolog 4 2 3 5
  • MutS Protein Homolog 4 3 4
  • HMSH4 3 4
  • MutS (E. Coli) Homolog 4 2
  • MutS Homolog 4 (E. Coli) 2
  • MSH4 5

External Ids for MSH4 Gene

Previous GeneCards Identifiers for MSH4 Gene

  • GC01P076382
  • GC01P075197
  • GC01P075678
  • GC01P075685
  • GC01P075974
  • GC01P076035
  • GC01P076262
  • GC01P074392

Summaries for MSH4 Gene

Entrez Gene Summary for MSH4 Gene

  • 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]

GeneCards Summary for MSH4 Gene

MSH4 (MutS Homolog 4) is a Protein Coding gene. Diseases associated with MSH4 include Fanconi Anemia, Complementation Group A and Premature Ovarian Failure 1. Among its related pathways are Meiosis and Cell Cycle, Mitotic. Gene Ontology (GO) annotations related to this gene include damaged DNA binding and mismatched DNA binding. An important paralog of this gene is MSH3.

UniProtKB/Swiss-Prot Summary for MSH4 Gene

  • Involved in meiotic recombination. Required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis.

Gene Wiki entry for MSH4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MSH4 Gene

Genomics for MSH4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MSH4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J075797 Promoter/Enhancer 1.1 EPDnew ENCODE 600.7 0.0 -45 0.1 IKZF1 POLR2A HNRNPUL1 RBFOX2 SMAD5 ZNF24 ELF4 FUS NRF1 NONO MSH4 SNORD45B RABGGTB
GH01J075796 Enhancer 0.8 ENCODE 600.7 +0.2 179 0.3 IKZF1 POLR2A PHF21A HNRNPUL1 RBFOX2 ZNF24 SMAD5 FUS NRF1 MGA MSH4 DLSTP1 lnc-RABGGTB-2 ASB17
GH01J075784 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 22.5 -8.9 -8938 7.7 ZNF629 REST ZNF512 LEF1 IKZF1 NFKBIZ POLR2A BACH1 JUND FOXA1 RABGGTB NONHSAG001852.2 SNORD45A SNORD45B SNORD45C MSH4 DLSTP1 ACADM lnc-RABGGTB-1
GH01J075722 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 11.6 -71.8 -71770 6 SP1 HNRNPL GATAD2A PRDM10 ZNF629 REST TFE3 SOX13 IKZF1 NFKBIZ ACADM ENSG00000230863 SLC44A5 lnc-SLC44A5-4 RABGGTB DLSTP1 SNORD45A SNORD45C MSH4 piR-33257
GH01J075615 Promoter/Enhancer 1.7 EPDnew FANTOM5 ENCODE CraniofacialAtlas 8.9 -181.1 -181081 1.4 PRDM10 ZNF692 FOXA1 PRDM1 ZIC2 ZSCAN4 POLR2A PATZ1 IRF2 CTCF SLC44A5 MSH4 piR-38352-010 AB372670-001 LHX8
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MSH4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MSH4

Top Transcription factor binding sites by QIAGEN in the MSH4 gene promoter:
  • AML1a
  • AP-4
  • C/EBPalpha
  • E4BP4
  • Evi-1
  • FOXO3
  • FOXO3a
  • FOXO3b
  • POU2F1
  • POU2F1a

Genomic Locations for MSH4 Gene

Genomic Locations for MSH4 Gene
chr1:75,796,882-75,913,242
(GRCh38/hg38)
Size:
116,361 bases
Orientation:
Plus strand
chr1:76,262,567-76,378,923
(GRCh37/hg19)
Size:
116,357 bases
Orientation:
Plus strand

Genomic View for MSH4 Gene

Genes around MSH4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MSH4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MSH4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MSH4 Gene

Proteins for MSH4 Gene

  • Protein details for MSH4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15457-MSH4_HUMAN
    Recommended name:
    MutS protein homolog 4
    Protein Accession:
    O15457
    Secondary Accessions:
    • Q5T4U6
    • Q8NEB3
    • Q9UNP8

    Protein attributes for MSH4 Gene

    Size:
    936 amino acids
    Molecular mass:
    104756 Da
    Quaternary structure:
    • Heterooligomer of MSH4 and MSH5.

neXtProt entry for MSH4 Gene

Post-translational modifications for MSH4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MSH4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for MSH4 Gene

Domains & Families for MSH4 Gene

Gene Families for MSH4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for MSH4 Gene

GenScript: Design optimal peptide antigens:
  • MutS protein homolog 4 (MSH4_HUMAN)
  • MutS homolog 4 (Q5ZEZ0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O15457

UniProtKB/Swiss-Prot:

MSH4_HUMAN :
  • Belongs to the DNA mismatch repair MutS family.
Family:
  • Belongs to the DNA mismatch repair MutS family.
genes like me logo Genes that share domains with MSH4: view

Function for MSH4 Gene

Molecular function for MSH4 Gene

UniProtKB/Swiss-Prot Function:
Involved in meiotic recombination. Required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis.
GENATLAS Biochemistry:
yeast meiosis-specific protein (Mut S homolog 4) expressed in testis and ovary,interacting with MSH5,not involved in mismatch repair

Phenotypes From GWAS Catalog for MSH4 Gene

Gene Ontology (GO) - Molecular Function for MSH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003677 DNA binding TAS 9299235
GO:0005515 protein binding IPI 16397227
GO:0005524 ATP binding IEA --
GO:0008094 DNA-dependent ATPase activity IBA 21873635
genes like me logo Genes that share ontologies with MSH4: view
genes like me logo Genes that share phenotypes with MSH4: view

Animal Models for MSH4 Gene

MGI Knock Outs for MSH4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MSH4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for MSH4 Gene

Localization for MSH4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MSH4 gene
Compartment Confidence
nucleus 5
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1

Gene Ontology (GO) - Cellular Components for MSH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000228 nuclear chromosome IBA 21873635
GO:0000793 condensed chromosome IEA --
GO:0000794 condensed nuclear chromosome IEA --
GO:0000795 synaptonemal complex IEA,IBA 21873635
GO:0005634 nucleus IEA,TAS 9299235
genes like me logo Genes that share ontologies with MSH4: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Subcellular locations from the Human Protein Atlas (HPA) for MSH4 Gene

Pathways & Interactions for MSH4 Gene

PathCards logo

SuperPathways for MSH4 Gene

SuperPathway Contained pathways
1 Meiosis
.73
2 Cell Cycle, Mitotic
genes like me logo Genes that share pathways with MSH4: view

Pathways by source for MSH4 Gene

3 Reactome pathways for MSH4 Gene

Gene Ontology (GO) - Biological Process for MSH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000712 resolution of meiotic recombination intermediates IBA 21873635
GO:0001541 ovarian follicle development IEA --
GO:0006298 mismatch repair IEA --
GO:0007129 synapsis IEA --
GO:0007131 reciprocal meiotic recombination TAS,IBA 21873635
genes like me logo Genes that share ontologies with MSH4: view

No data available for SIGNOR curated interactions for MSH4 Gene

Drugs & Compounds for MSH4 Gene

No Compound Related Data Available

Transcripts for MSH4 Gene

mRNA/cDNA for MSH4 Gene

1 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MSH4

Alternative Splicing Database (ASD) splice patterns (SP) for MSH4 Gene

No ASD Table

Relevant External Links for MSH4 Gene

GeneLoc Exon Structure for
MSH4

Expression for MSH4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MSH4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MSH4 Gene

This gene is overexpressed in Testis (x6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MSH4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MSH4

SOURCE GeneReport for Unigene cluster for MSH4 Gene:

Hs.216639

mRNA Expression by UniProt/SwissProt for MSH4 Gene:

O15457-MSH4_HUMAN
Tissue specificity: Testis and ovary specific.

Evidence on tissue expression from TISSUES for MSH4 Gene

  • Skin(2.2)
genes like me logo Genes that share expression patterns with MSH4: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MSH4 Gene

Orthologs for MSH4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MSH4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MSH4 30 31
  • 99.57 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MSH4 30 31
  • 94.04 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MSH4 30 31
  • 92.65 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 87 (a)
OneToMany
-- 31
  • 78 (a)
OneToMany
-- 31
  • 76 (a)
OneToMany
-- 31
  • 73 (a)
OneToMany
Mouse
(Mus musculus)
Mammalia Msh4 30 17 31
  • 83.46 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Msh4 30
  • 83.06 (n)
Oppossum
(Monodelphis domestica)
Mammalia MSH4 31
  • 65 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MSH4 30 31
  • 74.4 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MSH4 31
  • 80 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia msh4 30
  • 74.12 (n)
Zebrafish
(Danio rerio)
Actinopterygii msh4 30 31
  • 59.97 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea him-14 30 31 32
  • 46.69 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MSH4 30 31
  • 48.83 (n)
OneToOne
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F11022g 30
  • 47.05 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons MSH4 30
  • 47.51 (n)
Rice
(Oryza sativa)
Liliopsida Os07g0486000 30
  • 46.15 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 53 (a)
OneToOne
Species where no ortholog for MSH4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for MSH4 Gene

ENSEMBL:
Gene Tree for MSH4 (if available)
TreeFam:
Gene Tree for MSH4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MSH4: view image

Paralogs for MSH4 Gene

Paralogs for MSH4 Gene

(1) SIMAP similar genes for MSH4 Gene using alignment to 2 proteins:

  • MSH4_HUMAN
  • Q5ZEZ0_HUMAN
genes like me logo Genes that share paralogs with MSH4: view

Variants for MSH4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MSH4 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
709020 Likely Benign: not provided 75,878,258(+) A/G MISSENSE_VARIANT
767679 Benign: not provided 75,881,378(+) G/T INTRON_VARIANT
rs5745311 - p.Ala60Val
rs5745324 - p.Ala90Thr
rs5745325 - p.Ala97Thr

Additional dbSNP identifiers (rs#s) for MSH4 Gene

Structural Variations from Database of Genomic Variants (DGV) for MSH4 Gene

Variant ID Type Subtype PubMed ID
esv1103396 CNV deletion 17803354
esv1540402 CNV insertion 17803354
esv1749246 CNV insertion 17803354
esv1918463 CNV deletion 18987734
esv2475692 CNV insertion 19546169
esv2575184 CNV loss 19546169
esv2749996 CNV deletion 23290073
esv3586491 CNV loss 21293372
nsv1004669 CNV loss 25217958
nsv1466 CNV deletion 18451855
nsv472748 CNV novel sequence insertion 20440878
nsv519329 CNV gain 19592680
nsv954757 CNV deletion 24416366

Variation tolerance for MSH4 Gene

Residual Variation Intolerance Score: 11.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.68; 65.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MSH4 Gene

Human Gene Mutation Database (HGMD)
MSH4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MSH4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MSH4 Gene

Disorders for MSH4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for MSH4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
fanconi anemia, complementation group a
  • fanca
premature ovarian failure 1
  • pof1
lynch syndrome
  • colorectal cancer, hereditary nonpolyposis, type 1
- elite association - COSMIC cancer census association via MalaCards
Search MSH4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MSH4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with MSH4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MSH4 Gene

Publications for MSH4 Gene

  1. Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene. (PMID: 9299235) Paquis-Flucklinger V … Desnuelle C (Genomics 1997) 2 3 4 23
  2. Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent. (PMID: 20378615) Aston KI … Carrell DT (Human reproduction (Oxford, England) 2010) 3 41
  3. Genetic investigation of four meiotic genes in women with premature ovarian failure. (PMID: 18166824) Mandon-Pépin B … Fellous M (European journal of endocrinology 2008) 3 41
  4. Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women. (PMID: 19064572) Palmieri RT … Australian Ovarian Cancer Study Group (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2008) 3 41
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for MSH4 Gene

  • Signalway Proteins for MSH4

Sources for MSH4 Gene