Details for: MSH4

Gene ID: 4438

Symbol: MSH4

Ensembl ID: ENSG00000057468

Description: mutS homolog 4

Associated with

Cells (max top 100)

(Cell Significance Index and respective Thresholds are uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: skeletal muscle fiber (CL0008002)
    Fold Change: 1.5647
    Cell Significance Index: 40.2200
  • Cell Name: hippocampal granule cell (CL0001033)
    Fold Change: 0.6654
    Cell Significance Index: 44.7400
  • Cell Name: L2/3-6 intratelencephalic projecting glutamatergic neuron (CL4023040)
    Fold Change: 0.6422
    Cell Significance Index: 128.8300
  • Cell Name: transit amplifying cell of colon (CL0009011)
    Fold Change: 0.5901
    Cell Significance Index: 18.9000
  • Cell Name: type I muscle cell (CL0002211)
    Fold Change: 0.3672
    Cell Significance Index: 8.9600
  • Cell Name: GABAergic interneuron (CL0011005)
    Fold Change: 0.3532
    Cell Significance Index: 244.2700
  • Cell Name: cardiac muscle myoblast (CL0000513)
    Fold Change: 0.3266
    Cell Significance Index: 25.0700
  • Cell Name: obsolete caudal ganglionic eminence derived GABAergic cortical interneuron (CL4023070)
    Fold Change: 0.3025
    Cell Significance Index: 108.5000
  • Cell Name: hippocampal pyramidal neuron (CL1001571)
    Fold Change: 0.1808
    Cell Significance Index: 5.1600
  • Cell Name: indirect pathway medium spiny neuron (CL4023029)
    Fold Change: 0.1546
    Cell Significance Index: 6.8400
  • Cell Name: direct pathway medium spiny neuron (CL4023026)
    Fold Change: 0.1347
    Cell Significance Index: 5.1000
  • Cell Name: type II muscle cell (CL0002212)
    Fold Change: 0.0682
    Cell Significance Index: 1.1000
  • Cell Name: mesothelial cell of epicardium (CL0011019)
    Fold Change: 0.0474
    Cell Significance Index: 0.4100
  • Cell Name: forebrain neuroblast (CL1000042)
    Fold Change: 0.0412
    Cell Significance Index: 2.5300
  • Cell Name: neoplastic cell (CL0001063)
    Fold Change: 0.0332
    Cell Significance Index: 6.5800
  • Cell Name: Purkinje cell (CL0000121)
    Fold Change: 0.0206
    Cell Significance Index: 0.4500
  • Cell Name: cerebellar granule cell (CL0001031)
    Fold Change: 0.0193
    Cell Significance Index: 0.3300
  • Cell Name: basal epithelial cell of tracheobronchial tree (CL0002329)
    Fold Change: 0.0136
    Cell Significance Index: 0.3800
  • Cell Name: pigmented epithelial cell (CL0000529)
    Fold Change: 0.0041
    Cell Significance Index: 7.6800
  • Cell Name: anterior lens cell (CL0002223)
    Fold Change: 0.0003
    Cell Significance Index: 0.5200
  • Cell Name: lens epithelial cell (CL0002224)
    Fold Change: -0.0005
    Cell Significance Index: -0.7000
  • Cell Name: secondary lens fiber (CL0002225)
    Fold Change: -0.0011
    Cell Significance Index: -1.5600
  • Cell Name: intermediate cell of urothelium (CL4030055)
    Fold Change: -0.0034
    Cell Significance Index: -0.6100
  • Cell Name: pigmented ciliary epithelial cell (CL0002303)
    Fold Change: -0.0035
    Cell Significance Index: -0.5100
  • Cell Name: non-pigmented ciliary epithelial cell (CL0002304)
    Fold Change: -0.0131
    Cell Significance Index: -8.3400
  • Cell Name: pancreatic A cell (CL0000171)
    Fold Change: -0.0161
    Cell Significance Index: -11.9600
  • Cell Name: cortical interneuron (CL0008031)
    Fold Change: -0.0163
    Cell Significance Index: -0.3900
  • Cell Name: pulmonary alveolar epithelial cell (CL0000322)
    Fold Change: -0.0174
    Cell Significance Index: -13.1500
  • Cell Name: ciliary muscle cell (CL1000443)
    Fold Change: -0.0175
    Cell Significance Index: -7.9400
  • Cell Name: cell in vitro (CL0001034)
    Fold Change: -0.0201
    Cell Significance Index: -10.9600
  • Cell Name: dopaminergic neuron (CL0000700)
    Fold Change: -0.0215
    Cell Significance Index: -6.2000
  • Cell Name: type B pancreatic cell (CL0000169)
    Fold Change: -0.0220
    Cell Significance Index: -12.3900
  • Cell Name: eukaryotic cell (CL0000255)
    Fold Change: -0.0345
    Cell Significance Index: -1.5000
  • Cell Name: epithelial cell of small intestine (CL0002254)
    Fold Change: -0.0369
    Cell Significance Index: -6.0100
  • Cell Name: pvalb GABAergic cortical interneuron (CL4023018)
    Fold Change: -0.0400
    Cell Significance Index: -0.8500
  • Cell Name: transit amplifying cell of small intestine (CL0009012)
    Fold Change: -0.0439
    Cell Significance Index: -0.9100
  • Cell Name: retinal progenitor cell (CL0002672)
    Fold Change: -0.0469
    Cell Significance Index: -2.6300
  • Cell Name: basal cell of urothelium (CL1000486)
    Fold Change: -0.0487
    Cell Significance Index: -5.9900
  • Cell Name: pancreatic D cell (CL0000173)
    Fold Change: -0.0598
    Cell Significance Index: -12.6000
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: -0.0647
    Cell Significance Index: -11.0500
  • Cell Name: stromal cell of ovary (CL0002132)
    Fold Change: -0.0694
    Cell Significance Index: -9.5300
  • Cell Name: OFF midget ganglion cell (CL4033047)
    Fold Change: -0.0714
    Cell Significance Index: -0.8900
  • Cell Name: smooth muscle cell of sphincter of pupil (CL0002243)
    Fold Change: -0.0928
    Cell Significance Index: -9.6700
  • Cell Name: sst GABAergic cortical interneuron (CL4023017)
    Fold Change: -0.0999
    Cell Significance Index: -1.9800
  • Cell Name: tonsil germinal center B cell (CL2000006)
    Fold Change: -0.1003
    Cell Significance Index: -11.8300
  • Cell Name: corticothalamic-projecting glutamatergic cortical neuron (CL4023013)
    Fold Change: -0.1030
    Cell Significance Index: -3.2800
  • Cell Name: epithelial cell of stomach (CL0002178)
    Fold Change: -0.1051
    Cell Significance Index: -12.2500
  • Cell Name: medial ganglionic eminence derived interneuron (CL4023063)
    Fold Change: -0.1075
    Cell Significance Index: -1.5400
  • Cell Name: neuron (CL0000540)
    Fold Change: -0.1076
    Cell Significance Index: -1.0200
  • Cell Name: pancreatic ductal cell (CL0002079)
    Fold Change: -0.1087
    Cell Significance Index: -12.4600
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: -0.1092
    Cell Significance Index: -11.1500
  • Cell Name: lamp5 GABAergic cortical interneuron (CL4023011)
    Fold Change: -0.1092
    Cell Significance Index: -2.3600
  • Cell Name: ON midget ganglion cell (CL4033046)
    Fold Change: -0.1161
    Cell Significance Index: -1.4700
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: -0.1195
    Cell Significance Index: -5.5700
  • Cell Name: gut absorptive cell (CL0000677)
    Fold Change: -0.1258
    Cell Significance Index: -7.5600
  • Cell Name: L6b glutamatergic cortical neuron (CL4023038)
    Fold Change: -0.1275
    Cell Significance Index: -4.1800
  • Cell Name: cardiac muscle cell (CL0000746)
    Fold Change: -0.1382
    Cell Significance Index: -2.0400
  • Cell Name: kidney loop of Henle descending limb epithelial cell (CL1001021)
    Fold Change: -0.1400
    Cell Significance Index: -11.0900
  • Cell Name: VIP GABAergic cortical interneuron (CL4023016)
    Fold Change: -0.1405
    Cell Significance Index: -2.8200
  • Cell Name: L6 intratelencephalic projecting glutamatergic neuron of the primary motor cortex (CL4023050)
    Fold Change: -0.1567
    Cell Significance Index: -2.0900
  • Cell Name: near-projecting glutamatergic cortical neuron (CL4023012)
    Fold Change: -0.1644
    Cell Significance Index: -4.1000
  • Cell Name: eye photoreceptor cell (CL0000287)
    Fold Change: -0.1712
    Cell Significance Index: -10.7900
  • Cell Name: enterocyte of epithelium of small intestine (CL1000334)
    Fold Change: -0.1732
    Cell Significance Index: -4.9900
  • Cell Name: L5 extratelencephalic projecting glutamatergic cortical neuron (CL4023041)
    Fold Change: -0.1738
    Cell Significance Index: -6.0900
  • Cell Name: neural cell (CL0002319)
    Fold Change: -0.1740
    Cell Significance Index: -2.0300
  • Cell Name: luminal adaptive secretory precursor cell of mammary gland (CL4033057)
    Fold Change: -0.1772
    Cell Significance Index: -8.3300
  • Cell Name: lung endothelial cell (CL1001567)
    Fold Change: -0.1828
    Cell Significance Index: -9.5200
  • Cell Name: early pro-B cell (CL0002046)
    Fold Change: -0.1863
    Cell Significance Index: -12.0200
  • Cell Name: glycinergic neuron (CL1001509)
    Fold Change: -0.1908
    Cell Significance Index: -10.0200
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: -0.2095
    Cell Significance Index: -9.5000
  • Cell Name: slow muscle cell (CL0000189)
    Fold Change: -0.2139
    Cell Significance Index: -3.2000
  • Cell Name: regular atrial cardiac myocyte (CL0002129)
    Fold Change: -0.2151
    Cell Significance Index: -2.9000
  • Cell Name: retinal rod cell (CL0000604)
    Fold Change: -0.2215
    Cell Significance Index: -2.6400
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: -0.2218
    Cell Significance Index: -11.5200
  • Cell Name: chandelier pvalb GABAergic cortical interneuron (CL4023036)
    Fold Change: -0.2233
    Cell Significance Index: -4.6600
  • Cell Name: stratified epithelial cell (CL0000079)
    Fold Change: -0.2495
    Cell Significance Index: -9.1600
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: -0.2561
    Cell Significance Index: -9.0000
  • Cell Name: preadipocyte (CL0002334)
    Fold Change: -0.2593
    Cell Significance Index: -5.0600
  • Cell Name: glutamatergic neuron (CL0000679)
    Fold Change: -0.2726
    Cell Significance Index: -2.9700
  • Cell Name: GABAergic amacrine cell (CL4030027)
    Fold Change: -0.2753
    Cell Significance Index: -3.4200
  • Cell Name: fast muscle cell (CL0000190)
    Fold Change: -0.2802
    Cell Significance Index: -3.6700
  • Cell Name: paneth cell of epithelium of small intestine (CL1000343)
    Fold Change: -0.2825
    Cell Significance Index: -6.1200
  • Cell Name: fibro/adipogenic progenitor cell (CL0009099)
    Fold Change: -0.2852
    Cell Significance Index: -14.4100
  • Cell Name: cerebral cortex neuron (CL0010012)
    Fold Change: -0.2880
    Cell Significance Index: -2.7400
  • Cell Name: lens fiber cell (CL0011004)
    Fold Change: -0.3007
    Cell Significance Index: -9.5100
  • Cell Name: inhibitory interneuron (CL0000498)
    Fold Change: -0.3161
    Cell Significance Index: -3.7800
  • Cell Name: centrilobular region hepatocyte (CL0019029)
    Fold Change: -0.3176
    Cell Significance Index: -5.3500
  • Cell Name: L2/3 intratelencephalic projecting glutamatergic neuron (CL4030059)
    Fold Change: -0.3301
    Cell Significance Index: -4.4000
  • Cell Name: sncg GABAergic cortical interneuron (CL4023015)
    Fold Change: -0.3323
    Cell Significance Index: -6.5400
  • Cell Name: regular ventricular cardiac myocyte (CL0002131)
    Fold Change: -0.3342
    Cell Significance Index: -4.2900
  • Cell Name: basal cell of prostate epithelium (CL0002341)
    Fold Change: -0.3395
    Cell Significance Index: -9.2400
  • Cell Name: enteroendocrine cell of small intestine (CL0009006)
    Fold Change: -0.3432
    Cell Significance Index: -8.5800
  • Cell Name: leptomeningeal cell (CL0000708)
    Fold Change: -0.3504
    Cell Significance Index: -7.4900
  • Cell Name: cortical cell of adrenal gland (CL0002097)
    Fold Change: -0.3545
    Cell Significance Index: -9.5000
  • Cell Name: GABAergic neuron (CL0000617)
    Fold Change: -0.3574
    Cell Significance Index: -4.5100
  • Cell Name: fibroblast of dermis (CL0002551)
    Fold Change: -0.3655
    Cell Significance Index: -7.6500
  • Cell Name: obsolete epithelial cell of alveolus of lung (CL0010003)
    Fold Change: -0.3673
    Cell Significance Index: -9.1600
  • Cell Name: intestinal crypt stem cell of small intestine (CL0009017)
    Fold Change: -0.3714
    Cell Significance Index: -7.9100
  • Cell Name: hippocampal interneuron (CL1001569)
    Fold Change: -0.3724
    Cell Significance Index: -4.8300
  • Cell Name: keratinocyte (CL0000312)
    Fold Change: -0.3780
    Cell Significance Index: -9.4400

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Other Information

**Key Characteristics:** MSH4 is a homolog of the bacterial MutS protein, which is involved in the recognition of mismatched bases in DNA. The MSH4 protein is a heterodimeric complex, consisting of MSH4 and MSH5 subunits, which bind to mismatched bases and recruit the MSH2 subunit for excision and repair. MSH4 is also involved in the recognition of double-stranded breaks in DNA and the initiation of homologous recombination. Its expression is tightly regulated, with peak levels observed during meiosis and spermatogenesis. **Pathways and Functions:** MSH4 is a key component of the mismatch repair pathway, which is responsible for correcting errors in DNA replication and recombination. The MMR pathway involves the recognition of mismatched bases by MSH2 and MSH6, followed by the recruitment of the MSH4-MSH5 heterodimer for excision and repair. MSH4 also plays a critical role in the recognition of double-stranded breaks in DNA and the initiation of homologous recombination. Additionally, MSH4 is involved in the regulation of meiotic recombination and the formation of the synaptonemal complex, which is essential for proper chromosome pairing and segregation. **Clinical Significance:** Mutations in the MSH4 gene have been associated with an increased risk of cancer, particularly colorectal and endometrial cancer. Individuals with germline mutations in MSH4 are at higher risk of developing these cancers, highlighting the importance of MSH4 in maintaining genome stability. Furthermore, MSH4 has been implicated in the pathogenesis of certain genetic disorders, including Fanconi anemia, a rare genetic disorder characterized by bone marrow failure and increased risk of cancer. In conclusion, MSH4 plays a critical role in maintaining genome stability and reproductive health. Its involvement in the mismatch repair pathway, homologous recombination, and meiotic recombination processes highlights its importance in multiple biological processes. The clinical significance of MSH4 mutations underscores the need for further research into the molecular mechanisms underlying its function and the development of targeted therapies for individuals with germline mutations in this gene. **Implications for Human Health:** The study of MSH4 has significant implications for our understanding of human health and disease. The identification of MSH4 mutations has led to the development of targeted therapies for individuals with germline mutations, including immunotherapy and chemotherapy. Furthermore, the understanding of MSH4's role in genome stability and reproductive health has implications for the development of novel cancer therapies and the prevention of genetic disorders. In conclusion, MSH4 is a critical gene that plays a vital role in maintaining genome stability and reproductive health. Its involvement in the mismatch repair pathway, homologous recombination, and meiotic recombination processes highlights its importance in multiple biological processes. The clinical significance of MSH4 mutations underscores the need for further research into the molecular mechanisms underlying its function and the development of targeted therapies for individuals with germline mutations in this gene.

Genular Protein ID: 151945567

Symbol: MSH4_HUMAN

Name: MutS protein homolog 4

UniProtKB Accession Codes:

O15457 Q5T4U6 Q8NEB3 Q9UNP8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEBI 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 GO 15 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9299235

Title: Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene.

PubMed ID: 9299235

DOI: 10.1006/geno.1997.4857

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 28541421

Title: A homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiency.

PubMed ID: 28541421

DOI: 10.1093/hmg/ddx199

PubMed ID: 33437391

Title: A novel homozygous mutation in the meiotic gene MSH4 leading to male infertility due to non-obstructive azoospermia.

PubMed ID: 33437391

PubMed ID: 32741963

Title: Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.

PubMed ID: 32741963

DOI: 10.1038/s41436-020-0907-1

PubMed ID: 33448284

Title: Rare missense variant in MSH4 associated with primary gonadal failure in both 46, XX and 46, XY individuals.

PubMed ID: 33448284

DOI: 10.1093/humrep/deaa362

PubMed ID: 34755185

Title: Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes.

PubMed ID: 34755185

DOI: 10.1093/humrep/deab230

PubMed ID: 35090489

Title: Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia.

PubMed ID: 35090489

DOI: 10.1186/s12958-022-00900-x

Sequence Information:

  • Length: 936
  • Mass: 104756
  • Checksum: 5A82684379346441
  • Sequence:
    • MLRPEISSTS PSAPAVSPSS GETRSPQGPR YNFGLQETPQ SRPSVQVVSA STCPGTSGAA 
GDRSSSSSSL PCPAPNSRPA QGSYFGNKRA YAENTVASNF TFGASSSSAR DTNYPQTLKT 
PLSTGNPQRS GYKSWTPQVG YSASSSSAIS AHSPSVIVAV VEGRGLARGE IGMASIDLKN 
PQIILSQFAD NTTYAKVITK LKILSPLEII MSNTACAVGN STKLFTLITE NFKNVNFTTI 
QRKYFNETKG LEYIEQLCIA EFSTVLMEVQ SKYYCLAAVA ALLKYVEFIQ NSVYAPKSLK 
ICFQGSEQTA MIDSSSAQNL ELLINNQDYR NNHTLFGVLN YTKTPGGSRR LRSNILEPLV 
DIETINMRLD CVQELLQDEE LFFGLQSVIS RFLDTEQLLS VLVQIPKQDT VNAAESKITN 
LIYLKHTLEL VDPLKIAMKN CNTPLLRAYY GSLEDKRFGI ILEKIKTVIN DDARYMKGCL 
NMRTQKCYAV RSNINEFLDI ARRTYTEIVD DIAGMISQLG EKYSLPLRTS FSSARGFFIQ 
MTTDCIALPS DQLPSEFIKI SKVKNSYSFT SADLIKMNER CQESLREIYH MTYMIVCKLL 
SEIYEHIHCL YKLSDTVSML DMLLSFAHAC TLSDYVRPEF TDTLAIKQGW HPILEKISAE 
KPIANNTYVT EGSNFLIITG PNMSGKSTYL KQIALCQIMA QIGSYVPAEY SSFRIAKQIF 
TRISTDDDIE TNSSTFMKEM KEIAYILHNA NDKSLILIDE LGRGTNTEEG IGICYAVCEY 
LLSLKAFTLF ATHFLELCHI DALYPNVENM HFEVQHVKNT SRNKEAILYT YKLSKGLTEE 
KNYGLKAAEV SSLPPSIVLD AKEITTQITR QILQNQRSTP EMERQRAVYH LATRLVQTAR 
NSQLDPDSLR IYLSNLKKKY KEDFPRTEQV PEKTEE

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. You can zoom in with the mouse wheel for a closer view, and the text will adjust automatically if necessary. For the full schema, download it here.