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MSH6 mutS homolog 6 [ Homo sapiens (human) ]

Gene ID: 2956, updated on 3-Nov-2019

Summary

Official Symbol
MSH6provided by HGNC
Official Full Name
mutS homolog 6provided by HGNC
Primary source
HGNC:HGNC:7329
See related
Ensembl:ENSG00000116062 MIM:600678
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
GTBP; HSAP; p160; GTMBP; HNPCC5
Summary
This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
Expression
Ubiquitous expression in ovary (RPKM 15.4), testis (RPKM 14.1) and 25 other tissues See more
Orthologs

Genomic context

See MSH6 in Genome Data Viewer
Location:
2p16.3
Exon count:
12
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (47783082..47806954)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (48010221..48034092)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC440864 Neighboring gene NME/NM23 nucleoside diphosphate kinase 2 pseudogene Neighboring gene uncharacterized LOC105374589 Neighboring gene ribosomal protein L36a pseudogene 15 Neighboring gene F-box protein 11 Neighboring gene ribosomal protein S27a pseudogene 7 Neighboring gene uncharacterized LOC100506235

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in MSH6 that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Associated conditions

Description Tests
Endometrial carcinoma
MedGen: C0476089 OMIM: 608089 GeneReviews: Not available
Compare labs
Hereditary nonpolyposis colorectal cancer type 5
MedGen: C1833477 OMIM: 614350 GeneReviews: Not available
Compare labs
Turcot syndrome
MedGen: C0265325 OMIM: 276300 GeneReviews: Lynch Syndrome
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2015-11-16)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2015-11-16)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Genome-wide association study of smoking behaviours in patients with COPD.
NHGRI GWA Catalog

Pathways from BioSystems

  • BRCA1-associated genome surveillance complex (BASC), organism-specific biosystem (from KEGG)
    BRCA1-associated genome surveillance complex (BASC), organism-specific biosystemStructural complex; Genetic information processing; Repair system
  • BRCA1-associated genome surveillance complex (BASC), conserved biosystem (from KEGG)
    BRCA1-associated genome surveillance complex (BASC), conserved biosystemStructural complex; Genetic information processing; Repair system
  • Colorectal cancer, organism-specific biosystem (from KEGG)
    Colorectal cancer, organism-specific biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
  • Colorectal cancer, conserved biosystem (from KEGG)
    Colorectal cancer, conserved biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
  • Integrated Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Cancer Pathway, organism-specific biosystem
    Integrated Cancer Pathway
  • Mismatch Repair, organism-specific biosystem (from REACTOME)
    Mismatch Repair, organism-specific biosystemThe mismatch repair (MMR) system corrects single base mismatches and small insertion and deletion loops (IDLs) of unpaired bases. MMR is primarily associated with DNA replication and is highly conser...
  • Mismatch repair, organism-specific biosystem (from KEGG)
    Mismatch repair, organism-specific biosystemDNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preven...
  • Mismatch repair, organism-specific biosystem (from WikiPathways)
    Mismatch repair, organism-specific biosystemDNA mismatch repair is a system for recognizing and repairing erroneous insertion, deletion and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairin...
  • Mismatch repair, conserved biosystem (from KEGG)
    Mismatch repair, conserved biosystemDNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preven...
  • Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha), organism-specific biosystem (from REACTOME)
    Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha), organism-specific biosystemMSH2:MSH6 (MutSalpha) binds single base mismatches and unpaired loops of 1-2 nucleotides (reviewed in Edelbrock et al. 2013). Human cells contain about 6-fold more MSH2:MSH6 than MSH2:MSH3 (MutSbeta)...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Platinum drug resistance, organism-specific biosystem (from KEGG)
    Platinum drug resistance, organism-specific biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
  • Platinum drug resistance, conserved biosystem (from KEGG)
    Platinum drug resistance, conserved biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
  • Retinoblastoma (RB) in Cancer, organism-specific biosystem (from WikiPathways)
    Retinoblastoma (RB) in Cancer, organism-specific biosystemDescribes the role of retinoblastoma (RB) gene in cancer.
  • Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
    Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to ADP binding IDA
Inferred from Direct Assay
more info
PubMed 
ATP binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to ATP binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to ATPase activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA-dependent ATPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to MutLalpha complex binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to MutLalpha complex binding IDA
Inferred from Direct Assay
more info
PubMed 
chromatin binding IEA
Inferred from Electronic Annotation
more info
 
contributes_to double-stranded DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
four-way junction DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to four-way junction DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to guanine/thymine mispair binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to magnesium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
methylated histone binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to mismatched DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mismatched DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to mismatched DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to oxidized purine DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to oxidized purine DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
NOT protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to single guanine insertion binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to single thymine insertion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to single thymine insertion binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
DNA repair IDA
Inferred from Direct Assay
more info
PubMed 
determination of adult lifespan ISS
Inferred from Sequence or Structural Similarity
more info
 
interstrand cross-link repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intrinsic apoptotic signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
intrinsic apoptotic signaling pathway in response to DNA damage IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage ISS
Inferred from Sequence or Structural Similarity
more info
 
isotype switching ISS
Inferred from Sequence or Structural Similarity
more info
 
maintenance of DNA repeat elements IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NOT maintenance of DNA repeat elements IMP
Inferred from Mutant Phenotype
more info
PubMed 
meiotic mismatch repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
meiotic mismatch repair ISS
Inferred from Sequence or Structural Similarity
more info
 
mismatch repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mismatch repair IDA
Inferred from Direct Assay
more info
PubMed 
mismatch repair IGI
Inferred from Genetic Interaction
more info
PubMed 
mismatch repair IMP
Inferred from Mutant Phenotype
more info
PubMed 
mismatch repair TAS
Traceable Author Statement
more info
 
negative regulation of DNA recombination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of DNA recombination IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
pyrimidine dimer repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
response to UV ISS
Inferred from Sequence or Structural Similarity
more info
 
somatic hypermutation of immunoglobulin genes IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
somatic hypermutation of immunoglobulin genes ISS
Inferred from Sequence or Structural Similarity
more info
 
somatic recombination of immunoglobulin gene segments IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
somatic recombination of immunoglobulin gene segments ISS
Inferred from Sequence or Structural Similarity
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
 
MutSalpha complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
MutSalpha complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
mismatch repair complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nuclear chromatin IEA
Inferred from Electronic Annotation
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
DNA mismatch repair protein Msh6
Names
G/T mismatch-binding protein
mutS protein homolog 6
mutS-alpha 160 kDa subunit
sperm-associated protein

NCBI Reference Sequences (RefSeq)

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

  1. NG_007111.1 RefSeqGene

    Range
    4936..28807
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_219

mRNA and Protein(s)

  1. NM_000179.2NP_000170.1  DNA mismatch repair protein Msh6 isoform 1

    See identical proteins and their annotated locations for NP_000170.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1).
    Source sequence(s)
    BC071594, BC104665, DA857066, U28946
    Consensus CDS
    CCDS1836.1
    UniProtKB/Swiss-Prot
    P52701
    UniProtKB/TrEMBL
    Q3SWU9
    Related
    ENSP00000234420.4, ENST00000234420.9
    Conserved Domains (7) summary
    cd05837
    Location:88195
    MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
    COG0249
    Location:4071336
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
    pfam01624
    Location:407525
    MutS_I; MutS domain I
    pfam05188
    Location:538692
    MutS_II; MutS domain II
    pfam05190
    Location:9321024
    MutS_IV; MutS family domain IV
    pfam05192
    Location:739827
    MutS_III; MutS domain III
    cl21455
    Location:10911313
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  2. NM_001281492.1NP_001268421.1  DNA mismatch repair protein Msh6 isoform 2

    See identical proteins and their annotated locations for NP_001268421.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site and lacks two exons in the 5' coding region compared to variant 1. The resulting protein (isoform 2) is shorter but has the same N- and C-termini compared to isoform 1.
    Source sequence(s)
    AK293921, BC071594
    Consensus CDS
    CCDS62906.1
    UniProtKB/Swiss-Prot
    P52701
    Related
    ENSP00000446475.1, ENST00000540021.5
    Conserved Domains (6) summary
    COG0249
    Location:2771206
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
    pfam01624
    Location:277395
    MutS_I; MutS domain I
    pfam05188
    Location:408562
    MutS_II; MutS domain II
    pfam05190
    Location:802894
    MutS_IV; MutS family domain IV
    pfam05192
    Location:609697
    MutS_III; MutS domain III
    cl21455
    Location:9611183
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  3. NM_001281493.1NP_001268422.1  DNA mismatch repair protein Msh6 isoform 3

    See identical proteins and their annotated locations for NP_001268422.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon and initiates translation at a downstream start codon compared to variant 1. The resulting protein (isoform 3) is shorter and has a distinct N-terminus compared to isoform 1. Variants 3 and 4 encode the same protein (isoform 3).
    Source sequence(s)
    AC006509, BC071594
    Consensus CDS
    CCDS62907.1
    UniProtKB/Swiss-Prot
    P52701
    Related
    ENSP00000477844.1, ENST00000614496.4
    Conserved Domains (6) summary
    COG0249
    Location:1051034
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
    pfam01624
    Location:105223
    MutS_I; MutS domain I
    pfam05188
    Location:236390
    MutS_II; MutS domain II
    pfam05190
    Location:630722
    MutS_IV; MutS family domain IV
    pfam05192
    Location:437525
    MutS_III; MutS domain III
    cl21455
    Location:7891011
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  4. NM_001281494.1NP_001268423.1  DNA mismatch repair protein Msh6 isoform 3

    See identical proteins and their annotated locations for NP_001268423.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a dowstream start codon compared to variant 1. The encoded isoform (3) is shorter and has a distinct N-terminus compared to isoform 1. Variants 3 and 4 encode the same protein (isoform 3).
    Source sequence(s)
    AC006509, AK304735, BC071594
    Consensus CDS
    CCDS62907.1
    UniProtKB/Swiss-Prot
    P52701
    Related
    ENSP00000438580.1, ENST00000538136.1
    Conserved Domains (6) summary
    COG0249
    Location:1051034
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
    pfam01624
    Location:105223
    MutS_I; MutS domain I
    pfam05188
    Location:236390
    MutS_II; MutS domain II
    pfam05190
    Location:630722
    MutS_IV; MutS family domain IV
    pfam05192
    Location:437525
    MutS_III; MutS domain III
    cl21455
    Location:7891011
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    47783082..47806954
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024452819.1XP_024308587.1  DNA mismatch repair protein Msh6 isoform X1

    Conserved Domains (2) summary
    cd05837
    Location:88195
    MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
    COG0249
    Location:4071367
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
  2. XM_024452822.1XP_024308590.1  DNA mismatch repair protein Msh6 isoform X4

    Conserved Domains (1) summary
    COG0249
    Location:1051065
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
  3. XM_024452821.1XP_024308589.1  DNA mismatch repair protein Msh6 isoform X3

    Conserved Domains (2) summary
    cd05837
    Location:196
    MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
    COG0249
    Location:3081268
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
  4. XM_024452820.1XP_024308588.1  DNA mismatch repair protein Msh6 isoform X2

    Conserved Domains (2) summary
    cd05837
    Location:27134
    MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
    COG0249
    Location:3461306
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
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