MSH4 (mutS homolog 4)

Gene

• Entrez ID: 4438
• Gene name: MutS homolog 4
• Gene symbol: MSH4
• Synonyms (NCBI Gene): ASG, POF20, SPGF2
• Chromosome: 1
• Chromosome location: 1p31.1
• 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

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000793	Component	Condensed chromosome	IEA
GO:0000794	Component	Condensed nuclear chromosome	IEA
GO:0000795	Component	Synaptonemal complex	IEA
GO:0001541	Process	Ovarian follicle development	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	9299235
GO:0003690	Function	Double-stranded DNA binding	IBA
GO:0005515	Function	Protein binding	IPI	16397227, 22401567, 23725059
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	9299235
GO:0005694	Component	Chromosome	IEA
GO:0005694	Component	Chromosome	ISS
GO:0005713	Component	Recombination nodule	IEA
GO:0006298	Process	Mismatch repair	IEA
GO:0007129	Process	Homologous chromosome pairing at meiosis	IEA
GO:0007131	Process	Reciprocal meiotic recombination	IBA
GO:0007131	Process	Reciprocal meiotic recombination	TAS	9299235
GO:0007283	Process	Spermatogenesis	IEA
GO:0007292	Process	Female gamete generation	IEA
GO:0030983	Function	Mismatched DNA binding	IEA
GO:0051321	Process	Meiotic cell cycle	IEA
GO:0051321	Process	Meiotic cell cycle	IEA
GO:0140664	Function	ATP-dependent DNA damage sensor activity	IEA

Other IDs

• MIM: 602105
• HGNC: 7327
• e!Ensembl: ENSG00000057468

Protein

• UniProt ID: O15457
• Protein name: MutS protein homolog 4 (hMSH4)
• Protein function: Involved in meiotic recombination. Required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF05188	MutS_II	155 → 298	MutS domain II	Domain
  PF05192	MutS_III	315 → 627	MutS domain III	Domain
  PF05190	MutS_IV	493 → 587	MutS family domain IV	Domain
  PF00488	MutS_V	676 → 869	MutS domain V	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in testis (PubMed:33437391, PubMed:9299235). Also expressed in the ovary (PubMed:9299235). {ECO:0000269|PubMed:33437391, ECO:0000269|PubMed:9299235}.
• Sequence:

  MLRPEISSTSPSAPAVSPSSGETRSPQGPRYNFGLQETPQSRPSVQVVSASTCPGTSGAA
  GDRSSSSSSLPCPAPNSRPAQGSYFGNKRAYAENTVASNFTFGASSSSARDTNYPQTLKT
  PLSTGNPQRSGYKSWTPQVGYSASSSSAISAHSPSVIVAVVEGRGLARGEIGMASIDLKN
  PQIILSQFADNTTYAKVITKLKILSPLEIIMSNTACAVGNSTKLFTLITENFKNVNFTTI
  QRKYFNETKGLEYIEQLCIAEFSTVLMEVQSKYYCLAAVAALLKYVEFIQNSVYAPKSLK
  ICFQGSEQTAMIDSSSAQNLELLINNQDYRNNHTLFGVLNYTKTPGGSRRLRSNILEPLV
  DIETINMRLDCVQELLQDEELFFGLQSVISRFLDTEQLLSVLVQIPKQDTVNAAESKITN
  LIYLKHTLELVDPLKIAMKNCNTPLLRAYYGSLEDKRFGIILEKIKTVINDDARYMKGCL
  NMRTQKCYAVRSNINEFLDIARRTYTEIVDDIAGMISQLGEKYSLPLRTSFSSARGFFIQ
  MTTDCIALPSDQLPSEFIKISKVKNSYSFTSADLIKMNERCQESLREIYHMTYMIVCKLL
  SEIYEHIHCLYKLSDTVSMLDMLLSFAHACTLSDYVRPEFTDTLAIKQGWHPILEKISAE
  KPIANNTYVTEGSNFLIITGPNMSGKSTYLKQIALCQIMAQIGSYVPAEYSSFRIAKQIF
  TRISTDDDIETNSSTFMKEMKEIAYILHNANDKSLILIDELGRGTNTEEGIGICYAVCEY
  LLSLKAFTLFATHFLELCHIDALYPNVENMHFEVQHVKNTSRNKEAILYTYKLSKGLTEE
  KNYGLKAAEVSSLPPSIVLDAKEITTQITRQILQNQRSTPEMERQRAVYHLATRLVQTAR
  NSQLDPDSLRIYLSNLKKKYKEDFPRTEQVPEKTEE

• Sequence length: 936

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Genetic non-acquired premature ovarian failure	Likely pathogenic; Pathogenic	rs116141807, rs557796016, rs1430228393, rs777079867, rs1386320504, rs771456188	RCV001661757 RCV001661761 RCV001661772 RCV001663387 RCV001663388 RCV001663389	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Non-obstructive azoospermia	Likely pathogenic; Pathogenic	rs377712900, rs1651856824, rs751781089, rs149042353	RCV001255224 RCV001281660 RCV001281661 RCV001281662	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Oligospermia	Likely pathogenic; Pathogenic	rs377712900	RCV001255223	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian failure 20	Pathogenic; Likely pathogenic	rs774501542, rs377712900, rs149042353	RCV002260906 RCV002260684 RCV002264776	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian insufficiency	Likely pathogenic; Pathogenic	rs377712900	RCV001201398	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spermatogenic failure 2	Pathogenic; Likely pathogenic	rs1386320504, rs2100570734, rs2100513927, rs149910287, rs2100581757, rs377712900, rs149042353	RCV002260707 RCV002260907 RCV002260908 RCV002260909 RCV002260910 RCV002260683 RCV002264775	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
GONADAL DYSGENESIS, 46,XX	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN FAILURE, PREMATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TESTICULAR AZOOSPERMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Anodontia	Associate	37162286	★☆☆☆☆ Found in Text Mining only
Astrocytoma	Associate	25041856	★☆☆☆☆ Found in Text Mining only
Azoospermia	Associate	35090489	★☆☆☆☆ Found in Text Mining only
Azoospermia Nonobstructive	Associate	20075417	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	19781088	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	31127692	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms Hereditary Nonpolyposis	Associate	37162286	★☆☆☆☆ Found in Text Mining only
Distal myopathy Nonaka type	Associate	35090489	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Associate	28627638	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Associate	25041856	★☆☆☆☆ Found in Text Mining only
Glioma	Associate	25041856	★☆☆☆☆ Found in Text Mining only
Infertility	Associate	18706547	★☆☆☆☆ Found in Text Mining only
Infertility Male	Associate	18706547	★☆☆☆☆ Found in Text Mining only
Male Infertility with Large Headed Multiflagellar Polyploid Spermatozoa	Inhibit	20075417	★☆☆☆☆ Found in Text Mining only
Mesothelioma Malignant	Associate	34008015	★☆☆☆☆ Found in Text Mining only
Microsatellite Instability	Associate	32221012, 37162286	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	32957448, 37162286	★☆☆☆☆ Found in Text Mining only
Nervous System Neoplasms	Associate	25041856	★☆☆☆☆ Found in Text Mining only
Neurilemmoma	Associate	25041856	★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Associate	37620942	★☆☆☆☆ Found in Text Mining only
Primary Ovarian Insufficiency	Associate	36099812	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Associate	32221012, 36076047	★☆☆☆☆ Found in Text Mining only