U.S. flag

An official website of the United States government

MSH6 mutS homolog 6 [ Homo sapiens (human) ]

Gene ID: 2956, updated on 10-Dec-2024

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; AllianceGenome:HGNC:7329
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; MSH-6; HNPCC5; LYNCH5; MMRCS3
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

See MSH6 in Genome Data Viewer
Location:
2p16.3
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (47783145..47810101)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (47789083..47816050)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (48010284..48037240)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene RBIS pseudogene 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:47975285-47975438 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15740 Neighboring gene uncharacterized LOC105374589 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:48008525-48008706 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15741 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11467 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11468 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11469 Neighboring gene ribosomal protein L36a pseudogene 15 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15742 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15743 Neighboring gene F-box protein 11 Neighboring gene Sharpr-MPRA regulatory region 9679 Neighboring gene RPS27A pseudogene 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:48129098-48129367 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:48131440-48132226 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11470 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11471 Neighboring gene uncharacterized LOC100506235 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11472 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11473 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:48133799-48134583

Genomic regions, transcripts, and products

Expression

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 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
Lynch syndrome
MedGen: C4552100 GeneReviews: Lynch Syndrome
Compare labs
Lynch syndrome 5
MedGen: C1833477 OMIM: 614350 GeneReviews: Not available
Compare labs
Mismatch repair cancer syndrome 3
MedGen: C5436807 OMIM: 619097 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2021-10-13)

ClinGen Genome Curation PagePubMed
Triplosensitivity

No evidence available (Last evaluated 2021-10-13)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association study of smoking behaviours in patients with COPD.
EBI GWAS Catalog

Pathways from PubChem

Interactions

General gene information

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to ADP binding PubMed 
contributes_to ATP binding PubMed 
enables ATP-dependent DNA damage sensor activity  
enables ATP-dependent activity, acting on DNA PubMed 
contributes_to MutLalpha complex binding PubMed 
enables chromatin binding  
contributes_to double-stranded DNA binding PubMed 
enables enzyme binding PubMed 
contributes_to four-way junction DNA binding PubMed 
contributes_to guanine/thymine mispair binding PubMed 
contributes_to magnesium ion binding PubMed 
enables methylated histone binding PubMed 
contributes_to mismatched DNA binding PubMed 
enables mismatched DNA binding PubMed 
contributes_to oxidized purine DNA binding PubMed 
enables protein binding PubMed 
NOT enables protein homodimerization activity PubMed 
contributes_to single guanine insertion binding PubMed 
contributes_to single thymine insertion binding PubMed 
Process Evidence Code Pubs
involved_in DNA repair PubMed 
involved_in determination of adult lifespan  
involved_in intrinsic apoptotic signaling pathway  
involved_in intrinsic apoptotic signaling pathway in response to DNA damage  
involved_in isotype switching  
NOT involved_in maintenance of DNA repeat elements PubMed 
involved_in meiotic mismatch repair  
involved_in mismatch repair  
involved_in mismatch repair PubMed 
acts_upstream_of_or_within mismatch repair PubMed 
involved_in mismatch repair PubMed 
involved_in negative regulation of DNA recombination PubMed 
involved_in positive regulation of helicase activity PubMed 
involved_in response to UV  
involved_in somatic hypermutation of immunoglobulin genes  
involved_in somatic recombination of immunoglobulin gene segments  
involved_in spermatogenesis  
Component Evidence Code Pubs
located_in Golgi apparatus  
part_of MutSalpha complex  
part_of MutSalpha complex PubMed 
part_of MutSalpha complex PubMed 
located_in chromatin  
located_in cytosol  
located_in intracellular membrane-bounded organelle  
located_in nucleoplasm  
located_in nucleoplasm  
is_active_in nucleus  
located_in nucleus 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
mutS-like protein 6
sperm-associated protein

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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_000179.3NP_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, U54777
    Consensus CDS
    CCDS1836.1
    UniProtKB/Swiss-Prot
    B4DF41, B4E3I4, F5H2F9, O43706, O43917, P52701, Q8TCX4, Q9BTB5
    UniProtKB/TrEMBL
    A0A8V8TQJ0
    Related
    ENSP00000234420.5, ENST00000234420.11
    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_001281492.2NP_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/TrEMBL
    A0A8V8TQJ0
    Related
    ENSP00000446475.1, ENST00000540021.6
    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_001281493.2NP_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
    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_001281494.2NP_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
    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
  5. NM_001406795.1NP_001393724.1  DNA mismatch repair protein Msh6 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  6. NM_001406796.1NP_001393725.1  DNA mismatch repair protein Msh6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/Swiss-Prot
    B4DF41, B4E3I4, F5H2F9, O43706, O43917, P52701, Q8TCX4, Q9BTB5
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  7. NM_001406797.1NP_001393726.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
    Related
    ENSP00000501310.1, ENST00000673637.1
  8. NM_001406798.1NP_001393727.1  DNA mismatch repair protein Msh6 isoform 10

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
    Related
    ENSP00000514752.2, ENST00000700004.2
  9. NM_001406799.1NP_001393728.1  DNA mismatch repair protein Msh6 isoform 14

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  10. NM_001406800.1NP_001393729.1  DNA mismatch repair protein Msh6 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  11. NM_001406801.1NP_001393730.1  DNA mismatch repair protein Msh6 isoform 13

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  12. NM_001406802.1NP_001393731.1  DNA mismatch repair protein Msh6 isoform 9

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  13. NM_001406803.1NP_001393732.1  DNA mismatch repair protein Msh6 isoform 15

    Status: REVIEWED

    Source sequence(s)
    AC006509
  14. NM_001406804.1NP_001393733.1  DNA mismatch repair protein Msh6 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  15. NM_001406805.1NP_001393734.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  16. NM_001406806.1NP_001393735.1  DNA mismatch repair protein Msh6 isoform 14

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  17. NM_001406807.1NP_001393736.1  DNA mismatch repair protein Msh6 isoform 14

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  18. NM_001406808.1NP_001393737.1  DNA mismatch repair protein Msh6 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  19. NM_001406809.1NP_001393738.1  DNA mismatch repair protein Msh6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/Swiss-Prot
    B4DF41, B4E3I4, F5H2F9, O43706, O43917, P52701, Q8TCX4, Q9BTB5
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  20. NM_001406811.1NP_001393740.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  21. NM_001406812.1NP_001393741.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  22. NM_001406813.1NP_001393742.1  DNA mismatch repair protein Msh6 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  23. NM_001406814.1NP_001393743.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  24. NM_001406815.1NP_001393744.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  25. NM_001406816.1NP_001393745.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  26. NM_001406817.1NP_001393746.1  DNA mismatch repair protein Msh6 isoform 19

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TPJ4
    Related
    ENSP00000514749.1, ENST00000700000.1
  27. NM_001406818.1NP_001393747.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
    Related
    ENSP00000397484.2, ENST00000455383.6
  28. NM_001406819.1NP_001393748.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
    Related
    ENSP00000390382.2, ENST00000420813.6
  29. NM_001406820.1NP_001393749.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
    Related
    ENSP00000406248.2, ENST00000411819.2
  30. NM_001406821.1NP_001393750.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  31. NM_001406822.1NP_001393751.1  DNA mismatch repair protein Msh6 isoform 13

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  32. NM_001406823.1NP_001393752.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  33. NM_001406824.1NP_001393753.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  34. NM_001406825.1NP_001393754.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  35. NM_001406826.1NP_001393755.1  DNA mismatch repair protein Msh6 isoform 18

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A8V8TQJ0
  36. NM_001406827.1NP_001393756.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  37. NM_001406828.1NP_001393757.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  38. NM_001406829.1NP_001393758.1  DNA mismatch repair protein Msh6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006509
  39. NM_001406830.1NP_001393759.1  DNA mismatch repair protein Msh6 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC006509
    UniProtKB/TrEMBL
    A0A494C0M1, A0A8V8TQJ0, C9J7Y7, C9J8Y8, C9JH55
  40. NM_001406831.1NP_001393760.1  DNA mismatch repair protein Msh6 isoform 16

    Status: REVIEWED

    Source sequence(s)
    AC006509
  41. NM_001406832.1NP_001393761.1  DNA mismatch repair protein Msh6 isoform 20

    Status: REVIEWED

    Source sequence(s)
    AC006509
    Related
    ENST00000700005.1
  42. NM_001407362.1NP_001394291.1  DNA mismatch repair protein Msh6 isoform 17

    Status: REVIEWED

    Source sequence(s)
    AC006509

RNA

  1. NR_176256.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC006509
  2. NR_176257.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC006509
  3. NR_176258.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC006509
    Related
    ENST00000445503.5
  4. NR_176259.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC006509
  5. NR_176261.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC006509
    Related
    ENST00000699999.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    47783145..47810101
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    47789083..47816050
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
External link. Please review our privacy policy.