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MSH6 Gene

protein-coding   GIFtS: 71
GCID: GC02P047924

MutS Homolog 6

(Previous names: mutS (E. coli) homolog 6, mutS homolog 6 (E. coli))
(Previous symbol: GTBP)
  See MSH6-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
MutS Homolog 61 2     MutS (E. Coli) Homolog 61
GTBP1 2 3 5     MutS Homolog 6 (E. Coli)1
MutS-Alpha 160 KDa Subunit2 3     HSAP2
GTMBP2 3     DNA Mismatch Repair Protein Msh62
G/T Mismatch-Binding Protein2 3     Sperm-Associated Protein2
p1602 3     hMSH63
HNPCC52 5     

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 GC02P048010 GC02P047746


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for MSH6 Gene:
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)

GeneCards Summary for MSH6 Gene:
MSH6 (mutS homolog 6) is a protein-coding gene. Diseases associated with MSH6 include msh6-related lynch syndrome, and colorectal cancer, hereditary nonpolyposis, type 5. GO annotations related to this gene include magnesium ion binding and protein homodimerization activity.

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. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated
'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick
identification of mismatch repair to initiate the DNA mismatch repair reaction

Gene Wiki entry 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NT_022184.16  NC_018913.2  
Regulatory elements:
   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 plasmidMSH6 promoter sequence
   Search Chromatin IP Primers for MSH6

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing 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 GC02P047924:  view genomic region     (about GC identifiers)

Start:
47,922,669 bp from pter      End:
48,037,240 bp from pter
Size:
114,572 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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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
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

Explore proteomics data for MSH6 at MOPED

Post-translational modifications: 

  • The N-terminus is blocked1
  • Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway1
  • Ubiquitination2 at Lys334, Lys519, Lys610, Lys632, Lys728, Lys771, Lys824, Lys1296, Lys1315, Lys1325,
                                 Lys1352, Lys1358
  • Modification sites at PhosphoSitePlus

  • See MSH6 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_000170.1  NP_001268421.1  NP_001268422.1  NP_001268423.1  

    ENSEMBL proteins: 
     ENSP00000475605   ENSP00000405294   ENSP00000234420   ENSP00000410570   ENSP00000397484  
     ENSP00000390382   ENSP00000406248   ENSP00000446475   ENSP00000438580  

    MSH6 Human Recombinant Protein Products:

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    Novus Biologicals MSH6 Protein
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    ProSpec Recombinant Protein for MSH6
    Cloud-Clone Corp. Proteins for MSH6

     
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    antibodies-online proteins for MSH6 (2 products) 

     
    antibodies-online peptides for MSH6

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 10):
     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 domains:
    IPB000313 PWWP domain
    IPB007695 DNA mismatch repair protein MutS
    IPB007696 MutS III


    UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701
    Domain: The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3)
    (PubMed:23622243)
    Similarity: Belongs to the DNA mismatch repair MutS family
    Similarity: Contains 1 PWWP domain


    Find genes that share domains with MSH6           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: 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. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated
    'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick
    identification of mismatch repair to initiate the DNA mismatch repair reaction

         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)

         Gene Ontology (GO): Selected molecular function terms (see all 19):    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 ----
         
    Find genes that share ontologies with MSH6           About GenesLikeMe


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

         5 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Msh6):
     cellular  homeostasis/metabolism  integument  mortality/aging  tumorigenesis 

    Find genes that share phenotypes with MSH6           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for MSH6: Msh6tm1Htr Msh6tm1Rak

       genOway: Develop your customized and physiologically relevant rodent model for MSH6

    miRNA
    Products:
        
    miRTarBase miRNAs that target MSH6:
    hsa-mir-155-5p (MIRT000459), hsa-mir-215-5p (MIRT024435), hsa-mir-1 (MIRT023763), hsa-mir-615-3p (MIRT039671), hsa-mir-21-5p (MIRT005430), hsa-mir-324-5p (MIRT043139), hsa-mir-877-3p (MIRT037190), hsa-mir-192-5p (MIRT026596), hsa-mir-324-3p (MIRT042967), hsa-mir-26a-5p (MIRT050169), hsa-mir-106b-5p (MIRT044304), hsa-mir-23b-3p (MIRT046243), hsa-mir-193b-3p (MIRT016477), hsa-mir-484 (MIRT041744), hsa-mir-196b-5p (MIRT042692)

    Block miRNA regulation of human, mouse, rat MSH6 using miScript Target Protectors
    3 qRT-PCR 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
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    Predesigned siRNA for gene silencing in human, mouse, rat MSH6

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector: MSH6 (NM_000179)
    Browse Sino Biological Human cDNA Clones
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MSH6

    Cell Line
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MSH6


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MSH6_HUMAN, P52701: Nucleus. Chromosome. Note=Associates with H3K36me3 via its PWWP domain
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol4
    golgi apparatus4
    cytoskeleton2
    plasma membrane2
    extracellular1
    mitochondrion1
    vacuole1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000228nuclear chromosome IBA--
    GO:0000790nuclear chromatin IEA--
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--

    Find genes that share ontologies with MSH6           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, 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 Apr 2014 via Entrez Gene).
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    SuperPaths for MSH6 About   (see all 12)  
    See pathways by source

    SuperPathContained pathways About
    1Telomere C-strand (Lagging Strand) Synthesis
    Mismatch repair0.56
    Mismatch repair0.00
    Mismatch Repair in Eukaryotes0.54
    2Prostate Cancer
    Prostate Cancer0.32
    Integrated Cancer pathway0.32
    3Cell Cycle / Checkpoint Control
    Cell Cycle / Checkpoint Control0.32
    DNA Damage0.32
    4Endometrial cancer
    Colorectal cancer0.42
    5Glioma
    Signaling Pathways in Glioblastoma0.36


    Find genes that share SuperPaths with MSH6           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    4 Downloadable PowerPoint Slides of GeneGlobe 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

    Selected BioSystems Pathways for MSH6 (see all 6)
        Mismatch repair
    Integrated Breast Cancer Pathway
    Signaling Pathways in Glioblastoma
    Prostate Cancer
    RB in Cancer


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

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MSH6: 
              DNA Repair in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for MSH6

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

    Selected Interacting proteins for MSH6 (P527011, 2, 3 ENSP000002344204) via UniProtKB, MINT, STRING, and/or I2D (see all 921)
    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): Selected biological process terms (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--

    Find genes that share ontologies with MSH6           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for MSH6

    Selected Novoseek inferred 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)



    Find genes that share compounds with MSH6           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 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,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for MSH6 gene (4 alternative transcripts): 
    NM_000179.2  NM_001281492.1  NM_001281493.1  NM_001281494.1  

    Unigene Cluster for MSH6:

    MutS homolog 6 (E. coli)
    Hs.445052  [show with all ESTs]
    Unigene Representative Sequence: NM_000179
    12 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000607272 ENST00000454137 ENST00000606499 ENST00000445503(uc010fbj.3)
    ENST00000234420(uc002rwc.2 uc002rwd.4) ENST00000456246 ENST00000493177
    ENST00000455383 ENST00000420813 ENST00000411819 ENST00000540021 ENST00000538136(uc010yoj.2)

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    GenScript: all cDNA clones in your preferred vector: MSH6 (NM_000179)
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    Primer
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      QuantiFast Probe-based Assays in human, mouse, rat MSH6

    Additional mRNA 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 

    Selected AceView cDNA sequences (see all 282):

    AI341470 BM459523 BQ055289 BQ679566 CB108712 BX421128 AI540701 BM785404 
    BX100831 BG532313 BM835805 AI659557 BI086883 AA250813 AI433156 AI148344 
    NM_000179 U54777 AA830138 BQ059465 BQ050578 BI258792 BP373050 BP378633 

    GeneLoc Exon Structure

    Selected 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

    (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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    MSH6 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    MSH6 Expression
    About this image


    MSH6 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 8) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Thymus (Hematopoietic System)
             Double Negative 2 Thymocytes Thymus
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
    MSH6 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MSH6 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.445052
        Pathway & Disease-focused RT2 Profiler PCR Arrays including MSH6: 
              DNA Repair in human mouse rat
              Apoptosis 384HT in human mouse rat

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MSH6

    (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)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for MSH6 gene from Selected species (see all 26)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Msh61 , 5 mutS homolog 6 (E. coli)1, 5 84.44(n)1
    85.97(a)1
      17 (57.87 cM)5
    176881  NM_010830.21  NP_034960.11 
     879750505 
    chicken
    (Gallus gallus)
    Aves MSH61 mutS homolog 6 (E. coli) 67.95(n)
    69.81(a)
      421291  XM_419359.4  XP_419359.3 
    lizard
    (Anolis carolinensis)
    Reptilia MSH66
    Uncharacterized protein
    64(a)
    1 ↔ 1
    1(255181209-255205302)
    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
    Msh61
    41(a)3
    50.23(n)1
    45.84(a)1
      71B63
    396541  NM_140498.21  NP_648755.11 
    worm
    (Caenorhabditis elegans)
    Secernentea msh-61 , 3 DNA mismatch repair protein3
    msh-61
    40(a)3
    49.63(n)1
    41.46(a)1
      I(3449328-3462073)3
    1719141  NM_058762.41  NP_491163.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes MSH6(YDR097C)4
    MSH61
    Protein required for mismatch repair in mitosis and more4
    MSH61
    46.48(n)1
    36.52(a)1
      4(643837-640109)4
    8516711, 4  NP_010382.31  NP_010382.14 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons MSH61 MSH6 49.11(n)
    40.27(a)
      828147  NM_116438.1  NP_192116.1 
    rice
    (Oryza sativa)
    Liliopsida NM_189554.12   -- 73.52(n)    NM_189554.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MSH6 gene
    6 SIMAP similar genes for MSH6 using alignment to 10 protein entries:     MSH6_HUMAN (see all proteins):
    GTBP    MSH2    DKFZp434C1615    MSH5-SAPCD1    WHSC1    PSIP1

    Find genes that share paralogs with MSH6           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, 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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MSH6 (see all 1300)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs637506641,2,,4
    CHereditary non-polyposis colorectal cancer 5 (HNPCC5)4 untested147878007(+) TGATGA/C/TCAACA 2 A V mis10--------
    rs20209121,2,,4
    C,F,HColorectal/endometrial cancer4 pathogenic147895241(+) AGAAGT/CTGCTG 2 /A /V mis1 ese313Minor allele frequency- C:0.01NA MN EU NS EA 7003
    rs637502521,2,,4
    CHereditary non-polyposis colorectal cancer 5 (HNPCC5)4 untested147899582(+) TGCTGA/TAGTGT 2 E V mis10--------
    VAR_0439584
    Hereditary non-polyposis colorectal cancer 5 (HNPCC5)4--see VAR_0439582 R W mis40--------
    VAR_0439484
    Breast cancer4--see VAR_0439482 F S mis40--------
    VAR_0439624
    Colorectal/endometrial cancer4--see VAR_0439622 R H mis40--------
    rs10428201,2
    C,Fnon-pathogenic147878134(-) GCGGAG/TCGCGC 2 R syn14Minor allele frequency- T:0.08NS EU NA 466
    rs18009321,2
    C,F,O,Hnon-pathogenic147885569(+) TCACCA/GGGAGA 2 P syn133Minor allele frequency- G:0.15NA NS MN EA CSA WA EU 9319
    rs18009351,2
    C,F,O,Hnon-pathogenic147890601(+) GCAGAT/CGAAGC 2 /D syn133Minor allele frequency- C:0.22MN NS NA EA CSA WA EU 8997
    rs31363331,2
    C,F,Hnon-pathogenic147893953(+) TGGGGC/TTGGTA 2 L syn1 ese37Minor allele frequency- T:0.01NS EA NA 5226

    HapMap Linkage Disequilibrium report for MSH6 (47922669 - 48037240 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for MSH6:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv873999CNV Gain21882294

    Human Gene Mutation Database (HGMD): MSH6
    Locus Specific Mutation Databases (LSDB): MSH6

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing MSH6
    DNA2.0 Custom Variant and Variant Library Synthesis for MSH6

    (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.)
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    OMIM gene information: 600678   
    OMIM disorders: 614350  608089  276300  
    UniProtKB/Swiss-Prot: MSH6_HUMAN, P52701
  • Hereditary non-polyposis colorectal cancer 5 (HNPCC5) [MIM:614350]: An autosomal dominant disease
    associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to
    early-onset colorectal carcinoma (CRC) and extra-colonic tumors 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. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary
    predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II
    is characterized by 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. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families
    who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is
    strongly suspected. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus.
    Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other
    fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
  • Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: 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. Note=The disease is caused by mutations affecting the gene
    represented in this entry

  • 14 diseases for MSH6:    
    About MalaCards
    msh6-related lynch syndrome    colorectal cancer, hereditary nonpolyposis, type 5    endometrial cancer, familial    msh6-related turcot syndrome
    turcot syndrome    colorectal cancer 5    muir-torre syndrome    colorectal cancer, hereditary nonpolyposis, type 1
    lynch syndrome    attenuated familial adenomatous polyposis    familial adenomatous polyposis    colon cancer
    colorectal cancer    breast cancer

    8 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     Adenoma

    Find genes that share disorders with MSH6           About GenesLikeMe

    Selected Novoseek inferred 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
    GeneReviews: MSH6
    Genetic Association Database (GAD): MSH6
    Human Genome Epidemiology (HuGE) Navigator: MSH6 (105 documents)

    Export disorders for MSH6 gene to outside databases

    (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)
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    PubMed articles for MSH6 gene, integrated from 10 sources (see all 554):
    (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. (Int. J. Cancer 2004)
    2. MSH6 germline mutations are rare in colorectal cancer families. (PubMed id 14520694)1, 2, 4, 9 Peterlongo P....Ellis N.A. (Int. J. Cancer 2003)
    3. Mutations of GTBP in genetically unstable cells. (PubMed id 7604266)1, 2, 3, 9 Papadopoulos N.... Vogelstein B. (Science 1995)
    4. Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. (PubMed id 18033691)1, 2, 4, 9 Barnetson R.A....Dunlop M.G. (Hum. Mutat. 2008)
    5. Meta-analysis of MSH6 gene mutation frequency in colorectal and endometrial cancers. (PubMed id 19492230)1, 4, 9 Zhao Y.S....Zhu S. (J. Toxicol. Environ. Health Part A 2009)
    6. 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. (Am. J. Hum. Genet. 2002)
    7. Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts. (PubMed id 18269114)1, 4, 9 Devlin L.A....Morrison P.J. (Ulster Med J 2008)
    8. Association of MUTYH and MSH6 germline mutations in colorectal cancer patients. (PubMed id 19685280)1, 4, 9 GirA!ldez M.D....CastellvA--Bel S. (Fam. Cancer 2009)
    9. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management. (PubMed id 20028567)1, 4, 9 Ramsoekh D....Kuipers E.J. (Hered Cancer Clin Pract 2009)
    10. 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. (Am. J. Hum. Genet. 1999)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

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

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    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/books/NBK1116/?term=MSH6[genesymbol]
    Hereditary non-polyposis colorectal cancer dbhttp://www.nfdht.nl/
    NIEHS-SNPshttp://egp.gs.washington.edu/data/msh6/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
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    Patent Information for MSH6 gene:
    Search GeneIP for patents involving MSH6

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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