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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

MSH6 Gene

protein-coding   GIFtS: 70
GCID: GC02P048010

mutS homolog 6 (E. coli)

(Previous name: mutS (E. coli) homolog 6 )
(Previous symbol: GTBP)
 Explore 70 diseases affiliated with
MSH6 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for MSH6    

Aliases
for MSH6 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
MutS Homolog 6 (E. Coli)1 2     P1601
GTBP1 2 3 5     HNPCC52 5
MutS-Alpha 160 KDa Subunit2 3     MutS (E. Coli) Homolog 61
GTMBP2 3     HSAP2
G/T Mismatch-Binding Protein2 3     DNA Mismatch Repair Protein Msh62
HMSH61     Sperm-Associated Protein2

External Ids:    HGNC: 73291   Entrez Gene: 29562   Ensembl: ENSG000001160627   OMIM: 6006785   UniProtKB: P527013   

Export aliases for MSH6 gene to outside databases

Previous GC identifers: GC02P048026 GC02P048179 GC02P047984 GC02P047921 GC02P047746


Summaries
for MSH6 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for MSH6:
This gene encodes a protein similar to the MutS protein. 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 of this gene combines 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 have been identified in individuals with hereditary
nonpolyposis colon cancer (HNPCC) and endometrial cancer. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701
Function: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS
alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and
shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops
(IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to
be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis.
ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS
alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a
discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent
diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in
DNA homologous recombination repair

Gene Wiki entry for MSH6


Genomic Views
for MSH6 gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000002.11  NC_018913.1  NT_022184.15  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the MSH6 gene promoter:
         AhR   GR   Sp1   CUTL1   YY1   FOXO1a   GR-alpha   FOXO1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: MSH6 promoter sequence
   Search SABiosciences Chromatin IP Primers for MSH6

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat MSH6


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p16   Ensembl cytogenetic band:  2p16.3   HGNC cytogenetic band: 2p16

MSH6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MSH6 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02P048010:  view genomic region     (about GC identifiers)

Start:
 48,010,221 bp from pter      End:
 48,034,092 bp from pter
Size:
 23,872 bases      Orientation:
 plus strand

Proteins
for MSH6 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701 (See protein sequence)
Recommended Name: DNA mismatch repair protein Msh6  
Size: 1360 amino acids; 152786 Da
Subunit: Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a ternary complex with MutL alpha (MLH1-PMS1).
Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2,
MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process
changing throughout the cell cycle and within subnuclear domains. Interacts with ATR
Subcellular location: Nucleus
6 PDB 3D structures from and Proteopedia for MSH6:
2GFU (3D)        2O8B (3D)        2O8C (3D)        2O8D (3D)        2O8E (3D)        2O8F (3D)    
Secondary accessions: O43706 O43917 Q8TCX4 Q9BTB5
Alternative splicing: 2 isoforms:  P52701-1   P52701-2   

Explore the universe of human proteins at neXtProt for MSH6: NX_P52701

Post-translational modifications:

  • The N-terminus is blocked1
  • Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P52701

    • MSH6 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_000170.1  
    ENSEMBL proteins: 
     ENSP00000234420   ENSP00000405294   ENSP00000410570   ENSP00000397484   ENSP00000390382  
     ENSP00000406248   ENSP00000446475   ENSP00000438580  

    Human Recombinant Protein Products: 
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    OriGene Custom Protein Services for MSH6 
    GenScript Custom Purified and Recombinant Proteins Services for MSH6
    Novus Biologicals MSH6 Proteins
    Browse Sino Biological Recombinant Proteins
    ProSpec Recombinant Protein for MSH6
    Uscn Proteins for MSH6

    Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000228nuclear chromosome IBA--
    GO:0000790nuclear chromatin IEA--
    GO:0032301MutSalpha complex IDA8942985


    MSH6 for ontologies           About GeneDecksing



    MSH6 Antibody Products: 
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    Abcam antibodies for MSH6 
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    ThermoFisher Antibody for MSH6

    Assay Products for MSH6: 
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    Uscn ELISAs and CLIAs for MSH6

    Protein Domains /
    Families
    for MSH6 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    MSH6 for domains           About GeneDecksing

    5/9 InterPro domains/families (see all 9):
     IPR007861 DNA_mismatch_repair_MutS_clamp
     IPR007696 DNA_mismatch_repair_MutS_core
     IPR007695 DNA_mismatch_repair_MutS-lik_N
     IPR015536 DNA_mismatch_repair_MSH6_C
     IPR017261 DNA_mismatch_repair_Msh6

    Graphical View of Domain Structure for InterPro Entry P52701

    ProtoNet protein and cluster: P52701

    3 Blocks protein families:
    IPB000313 PWWP domain
    IPB007695 DNA mismatch repair protein MutS
    IPB007696 MutS III


    UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701
    Similarity: Belongs to the DNA mismatch repair MutS family
    Similarity: Contains 1 PWWP domain


    Function
    for MSH6 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701
    Function: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS
    alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and
    shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops
    (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to
    be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis.
    ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS
    alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a
    discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent
    diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in
    DNA homologous recombination repair

         Genatlas biochemistry entry for MSH6:
    must S (E coli) homolog 6,GT binding protein,complexing with MSH2 in mismatch repair (MUTS alpha
    heterodimer),functioning as a molecular switch between ADP and ATP bound forms,selective for repair or GT mispair and
    single deplaced bases,with two alternatively spliced isoforms,GTBPN,mutated in gastric carcinomas in association with
    microsatellite mutator phenotype (MMP),deleted in sporadic colorectal cancer (early onset)

    miRNA
    Products:            		miRTarBase miRNAs that target MSH6:
    hsa-mir-155 (MIRT000459), hsa-mir-21 (MIRT005430)

    OriGene 3'-UTR Clone: MSH6
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MSH6
    3 QIAGEN miScript miRNA Assays for microRNAs that regulate MSH6:
    hsa-miR-142-5p hsa-miR-561 hsa-miR-409-3p
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for MSH6 (see all 4)
    OriGene shRNA RFP: MSH6
    OriGene siRNA: MSH6
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MSH6

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for MSH6

    Clone
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    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for MSH6 (see all 2)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for MSH6 (see all 2)
    OriGene custom cloning services – gene synthesis, subcloning, mutagenesis, variant library, vector shuttling 
    GenScript: all cDNA clones in your preferred vector: MSH6 (NM_000179)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MSH6
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MSH6 

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for MSH6
    Search LifeMap BioReagents cell lines for MSH6

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MSH6

    Gene Ontology (GO): 5/18 molecular function terms (GO ID links to tree view) (see all 18):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287contributes to magnesium ion binding IDA16403449
    GO:0000400contributes to four-way junction DNA binding IDA12034830
    GO:0003677DNA binding ----
    GO:0003682chromatin binding IEA--
    GO:0003684damaged DNA binding ----


    MSH6 for ontologies           About GeneDecksing


    1 GenomeRNAi human phenotype for MSH6:
     Increased cell number in G2M,  

    Animal Models:
         Mouse knock-outs for MSH6: Msh6tm1Htr Msh6tm1Rak
         5 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Msh6):
     cellular  homeostasis/metabolism  integument  mortality/aging  tumorigenesis 

    MSH6 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for MSH6 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/12 super-pathways (see all 12) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Lagging Strand Synthesis
    		Mismatch repair0.48
    		Mismatch repair0.17
    		Mismatch Repair in Eukaryotes0.33
    2Formation of RNA Pol II elongation complex
    		DNA damage_Role of Brca1 and Brca2 in DNA repair0.17
    		DNA damage Role of Brca1 and Brca2 in DNA repair0.17
    3DNA Damage
    		DNA Damage1.00
    4Cell Cycle / Checkpoint Control
    		Cell Cycle / Checkpoint Control1.00
    5BRCA1 Pathway
    		BRCA1 Pathway1.00

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 EMD Millipore Pathway for MSH6
        DNA damage Role of Brca1 and Brca2 in DNA repair

    4 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for MSH6
        Mismatch Repair in Eukaryotes
    BRCA1 Pathway
    DNA Repair Mechanisms
    Colorectal Cancer Metastasis

    2 Cell Signaling Technology (CST) Pathways for MSH6
        Cell Cycle / Checkpoint Control
    DNA Damage

    1 GeneGo (Thomson Reuters) Pathway for MSH6
        DNA damage Role of Brca1 and Brca2 in DNA repair

    4 BioSystems Pathways for MSH6 
        Integrated Breast Cancer Pathway
    Signaling Pathways in Glioblastoma
    Mismatch repair
    Integrated Cancer pathway


    3         Kegg Pathways  (Kegg details for MSH6):
        Mismatch repair
    Pathways in cancer
    Colorectal cancer


    MSH6 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for MSH6

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/832 Interacting proteins for MSH6 (P527011, 2, 3 ENSP000002344204) via UniProtKB, MINT, STRING, and/or I2D (see all 832)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    RUVBL2Q9Y2302, 3, ENSP000002214134MINT-7945693 MINT-7947479 I2D: score=4 STRING: ENSP00000221413
    SMARCD1Q96GM52, 3MINT-7945693 MINT-7947479 I2D: score=5 
    MLH1P406922, 3, ENSP000002317904MINT-7945693 I2D: score=3 STRING: ENSP00000231790
    BLMP541322, 3, ENSP000003472324MINT-7945693 I2D: score=1 STRING: ENSP00000347232
    DNAJA1P316892, 3MINT-7945693 MINT-7947479 I2D: score=1 
    About this table

    Gene Ontology (GO): 5/15 biological process terms (GO ID links to tree view) (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000710meiotic mismatch repair ISS--
    GO:0006200ATP catabolic process IDA16403449
    GO:0006281DNA repair IDA8942985
    GO:0006298mismatch repair IMP8782829
    GO:0007131reciprocal meiotic recombination IBA--


    MSH6 for ontologies           About GeneDecksing



    Drugs & Compounds
    for MSH6 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    MSH6 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for MSH6
    10/11 Novoseek chemical compound relationships for MSH6 gene (see all 11)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    mononucleotide 77 11 10918391 (2), 11054716 (1), 8805365 (1), 10934138 (1) (see all 8)
    crcs 68.4 4 17117178 (2), 15887099 (1), 11306449 (1)
    o6-methylguanine 62.7 2 10954713 (2)
    n-methyl-n'-nitrosourea 27.1 1 10954713 (1)
    tyrosine 3.92 1 7739521 (1)
    cisplatin 1.12 6 19484784 (2), 17938272 (1), 9889125 (1)
    threonine 0 1 8617235 (1)
    doxorubicin 0 3 10037468 (2), 9889125 (1)
    biotin 0 3 16540742 (2), 12610360 (1)
    paraffin 0 1 12400605 (1)

    Search CenterWatch for drugs/clinical trials and news about MSH6 

    Transcripts
    for MSH6 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    REFSEQ mRNAs for MSH6 gene: 
    NM_000179.2  

    Unigene Cluster for MSH6:

    MutS homolog 6 (E. coli)
    Hs.445052  [show with all ESTs]
    Unigene Representative Sequence: NM_000179
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000234420(uc002rwc.2 uc002rwd.4) ENST00000445503(uc010fbj.3)
    ENST00000456246 ENST00000493177 ENST00000455383 ENST00000420813 ENST00000411819
    ENST00000540021 ENST00000538136(uc010yoj.2)

    miRNA
    Products:             		 OriGene 3'-UTR Clone: MSH6
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MSH6
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    hsa-miR-142-5p hsa-miR-561 hsa-miR-409-3p
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    OriGene shRNA RFP: MSH6
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    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MSH6
    Clone
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    Primer
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      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat MSH6

    Additional cDNA sequence: 

    AK130683.1 AK293921.1 AK304735.1 AK308392.1 BC004246.1 BC071594.1 BC104665.1 D89646.1 
    U28946.1 U54777.2 

    16 DOTS entries:

    DT.101958448  DT.91759465  DT.419083  DT.100798420  DT.95229340  DT.109348  DT.95214649  DT.95229311 
    DT.102836851  DT.92005749  DT.120935256  DT.40106377  DT.40133304  DT.450978  DT.95229350  DT.97860065 

    24/282 AceView cDNA sequences (see all 282):

    BQ055289 CB127844 U28946 AU132390 CA425660 AA321991 BQ059465 AA470117 
    AA250807 BQ679566 BC040724 AA226977 AI341470 AA830138 AI079451 BF594315 
    BQ772835 BU187497 BI258792 CB160008 BM835805 AU133348 BM770619 AI433156 

    GeneLoc Exon Structure

    5/9 Alternative Splicing Database (ASD) splice patterns (SP) for MSH6 (see all 9)    About this scheme

    ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c · 8d ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14
    SP1:                                -     -     -     -                                         -                                       
    SP2:                                -     -     -     -                 -                       -                                       
    SP3:                                -     -     -     -                                                                                 
    SP4:                          -     -     -     -     -                                                                                 
    SP5:                                            -     -                                                                                 


    ECgene alternative splicing isoforms for MSH6

    Expression
    for MSH6 gene

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    MSH6 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    MSH6 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    Stem Cell Differentiation: 1 LifeMap Cell 
    NameCategory
    Definitive endoderm-like cells (A scalable, suspensi...)
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See MSH6 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for MSH6

    SOURCE GeneReport for Unigene cluster: Hs.445052
        SABiosciences Expression via Pathway-Focused PCR Arrays including MSH6: 
              DNA Repair in human mouse rat
              Apoptosis 384HT in human mouse rat

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    In Situ
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    Orthologs
    for MSH6 gene

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section
    This gene was present in the last universal common ancestor (LUCA).

    Orthologs for MSH6 gene from 10/40 species (see all 40)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves MSH61 mutS homolog 6 (E. coli) 68.04(n)
    69.57(a)    		   421291  XM_419359.3  XP_419359.3 
    lizard
    (Anolis carolinensis)    		 Reptilia MSH66
    		 --
    		 64(a)
    		 1 ↔ 1
    		 1(255192672-255205302)
    African clawed frog
    (Xenopus laevis)    		 Amphibia CA794059.12   -- 76.38(n)    CA794059.1 
    zebrafish
    (Danio rerio)    		 Actinopterygii msh62 mutS homolog 6 76.47(n)   260437  AF412834.1 
    fruit fly
    (Drosophila melanogaster)    		 Insecta CG70033
    Msh61    		 DNA repair3
    CG7003-PA1    		 41(a)3
    49.34(n)1
    44.23(a)1    		   71B63
    396541  NM_140498.11  NP_648755.11 
    worm
    (Caenorhabditis elegans)    		 Secernentea msh-61 , 3 DNA mismatch repair protein3
    Protein MSH-61    		 40(a)3
    48.77(n)1
    40.31(a)1    		   I(3449328-3462073)3
    1719141  NM_058762.31  NP_491163.11 
    baker's yeast
    (Saccharomyces cerevisiae)    		 Saccharomycetes MSH6(YDR097C)4
    MSH61    		 Protein required for mismatch repair in mitosis and more4
    Msh6p1    		 46.34(n)1
    36.14(a)1    		   4(643837-640109)4
    8516711, 4  NP_010382.31  NP_010382.14 
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons MSH61 DNA mismatch repair protein Msh6-1 48.85(n)
    40.06(a)    		   828147  NM_116438.1  NP_192116.1 
    rice
    (Oryza sativa)    		 Liliopsida NM_189554.12   -- 73.52(n)    NM_189554.1 
    E. coli
    (Escherichia coli)    		 Gamma proteobacteria mutS6
    		 methyl-directed mismatch repair protein
    		 27(a)
    		 possible ortholog
    		 Chromosome(2855115-2857676)


    ENSEMBL Gene Tree for MSH6 (if available)
    TreeFam Gene Tree for MSH6 (if available) 

    Paralogs
    for MSH6 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    		  --

    Genomic Variants
    for MSH6 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1004 NCBI SNPs in MSH6 are shown (see all 1004)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 2 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs22290181,2
    		C,F,Hnon-pathogenic47770124(+) ATTACA/G/TTTCCT 2 -- ds5001 ese310MN NA NS 4990
    rs10428201,2
    		C,F,non-pathogenic48010558(-) GCGGAG/TCGCGC 2 R syn14Minor allele frequency- T:0.08NS EU NA 466
    rs18009321,2
    		C,F,O,H,non-pathogenic48018081(+) TCACCA/GGGAGA 2 P syn133Minor allele frequency- G:0.15NA NS MN EA CSA WA EU 9319
    rs18009351,2
    		C,F,O,H,non-pathogenic48023115(+) GCAGAT/CGAAGC 2 /D syn133Minor allele frequency- C:0.22MN NS NA EA CSA WA EU 8997
    rs18009371,2
    		C,F,H,non-pathogenic48025764(+) ACTTAA/C/TGTAAC 3 * Y stg1 syn1 ese316NA NS MN EU EA 7020
    rs31363331,2
    		C,F,H,non-pathogenic48026467(+) TGGGGC/TTGGTA 2 L syn1 ese37Minor allele frequency- T:0.01NS EA NA 5226
    rs20209131,2
    		C,F,H,non-pathogenic48027375(+) ACAAAT/CGGTTC 2 /N syn121Minor allele frequency- C:0.02NA NS MN EA WA EU 8159
    rs20209101,2
    		C,F,H,non-pathogenic48030692(+) AAGACT/ATTTTT 2 /T syn130Minor allele frequency- A:0.03NA NS MN EA EU 9055
    rs31363671,2
    		C,F,A,H,non-pathogenic48033551(+) CTTCTG/CTTGCT 1 -- int134Minor allele frequency- C:0.16NS NA MN EA WA CSA 2951
    rs20209121,2
    		C,F,H,pathogenic48027755(+) AGAAGT/CTGCTG 2 /A /V mis1 ese313Minor allele frequency- C:0.01NA MN EU NS EA 7003

    HapMap Linkage Disequilibrium report for MSH6 (48010221 - 48034092 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for MSH6: --
    Human Gene Mutation Database (HGMD): MSH6

    Locus Specific Mutation Databases (LSDB): MSH6

    SABiosciences Cancer Mutation PCR Assays
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    Disorders / Diseases
    for MSH6 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    MSH6 for disorders           About GeneDecksing

    OMIM gene information: 600678   
    OMIM disorders: 608089  276300  
    UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701
  • Defects in MSH6 are the cause of hereditary non-polyposis colorectal cancer type 5 (HNPCC5) [MIM:614350].
    • Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype
    (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2
    genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility.
    It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers
    of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of
    inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed
    adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal
    cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk
    for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in
    addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected
    by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more
    colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. MSH6 mutations
    appear to be associated with atypical HNPCC and in particular with development of endometrial carcinoma or atypical
    endometrial hyperplasia, the presumed precursor of endometrial cancer. Defects in MSH6 are also found in familial
    colorectal cancers (suspected or incomplete HNPCC) that do not fulfill the Amsterdam criteria for HNPCC
  • Defects in MSH6 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089]
  • Defects in MSH6 are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:276300]; also known as Turcot
    • syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by
    malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts,
    hyperpigmented and cafe au lait spots

    20/70 diseases for MSH6 (see all 70):    About MalaCards
    cafe-au-lait spots    muir-torre syndrome    endometrial cancer    colorectal cancer, hereditary nonpolyposis, type 5
    colon cancer    familial adenomatous polyposis    attenuated familial adenomatous polyposis    sebaceous gland neoplasm
    fibrous histiocytoma    malignant fibrous histiocytoma    turcot syndrome    non-hodgkin lymphoma
    lynch syndrome    endometrial cancer, familial    colonic polyps    polyposis
    histiocytoma    systemic lupus erythematosus    colorectal cancer    myotonic dystrophy

    7 diseases from the University of Copenhagen DISEASES database for MSH6:
    Lynch syndrome     Colorectal cancer     Endometrial cancer     Carcinoma
    Familial adenomatous polyposis     Small intestine carcinoma     Ovarian cancer

    10/42 Novoseek disease relationships for MSH6 gene (see all 42)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lynch syndrome 96.2 32 18625694 (3), 19526325 (2), 19459153 (2), 10404064 (1) (see all 25)
    microsatellite instability 94.7 51 17117178 (3), 12019211 (1), 16203774 (1), 16879751 (1) (see all 43)
    colorectal cancer 88 218 19492230 (5), 11333868 (5), 18067074 (5), 17117178 (4) (see all 99)
    endometrial cancer 84.4 34 19492230 (5), 15805151 (3), 18269114 (3), 14961575 (2) (see all 23)
    hereditary nonpolyposis colon cancer 83.1 2 16237223 (1), 15184898 (1)
    muir-torre syndrome 76.6 1 18270343 (1)
    germ-line mutation 75.1 18 18331697 (3), 11245474 (3), 15872200 (2), 16885385 (2) (see all 11)
    colorectal carcinoma 68.3 4 10965560 (1), 14871813 (1), 15613860 (1), 10537275 (1)
    cancer 63.2 57 16106253 (4), 15236168 (3), 20028567 (3), 10545954 (2) (see all 40)
    endometrial carcinoma 63.1 7 11054716 (2), 20028567 (2), 18625694 (1), 15350299 (1)

    GeneTests: MSH6
    Hereditary Non-Polyposis Colon Cancer

    Genetic Association Database (GAD): MSH6
    Human Genome Epidemiology (HuGE) Navigator: MSH6 (105 documents)

    Export disorders for MSH6 gene to outside databases

    Publications
    for MSH6 gene

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for MSH6 gene, integrated from 9 sources (see all 528):
    (articles sorted by number of sources associating them with MSH6)    		    Utopia: connect your pdf to the dynamic
    world of online information

    1. Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden. (PubMed id 14961575)1, 2, 4, 9 Cederquist K.... Groenberg H. (2004)
    2. MSH6 germline mutations are rare in colorectal cancer families. (PubMed id 14520694)1, 2, 4, 9 Peterlongo P....Ellis N.A. (2003)
    3. Mutations of GTBP in genetically unstable cells. (PubMed id 7604266)1, 2, 3, 9 Papadopoulos N.... Vogelstein B. (1995)
    4. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. (PubMed id 11709755)1, 2, 9 Berends M.J.W.... Kleibeuker J.H. (2002)
    5. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. (PubMed id 10521294)1, 2, 9 Wu Y....Hofstra R.M.W. (1999)
    6. The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers. (PubMed id 16106253)1, 4, 9 Lawes D.A....Boulos P.B. (2005)
    7. Eight novel MSH6 germline mutations in patients with familial and nonfamilial colorectal cancer selected by loss of protein expression in tumor tissue. (PubMed id 14974087)1, 2, 9 Plaschke J.... Schackert H.K. (2004)
    8. No MSH6 germline mutations in breast cancer families with colorectal and/or endometrial cancer. (PubMed id 15805151)1, 4, 9 Vahteristo P....Nevanlinna H. (2005)
    9. Germ-line msh6 mutations in colorectal cancer families. (PubMed id 10537275)1, 2, 9 Kolodner R.D.... Li F.P. (1999)
    10. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. (PubMed id 7604265)1, 2, 9 Palombo F.... Jiricny J. (1995)

    External Searches for MSH6 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
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      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing MSH6 gene

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 2956 HGNC: 7329 AceView: MSH6 Ensembl:ENSG00000116062 euGenes: HUgn2956
    ECgene: MSH6 Kegg: 2956 H-InvDB: MSH6

    Other Databases showing MSH6 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing MSH6 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for MSH6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MSH6 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MSH6
    Hereditary non-polyposis colorectal cancer dbhttp://www.nfdht.nl/
    NIEHS-SNPshttp://egp.gs.washington.edu/data/msh6/

    Intellectual Property
    for MSH6 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		Patent Information for MSH6 gene:
    Search GeneIP for patents involving MSH6

    GeneCards and IP:
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