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MLH1 Gene

protein-coding   GIFtS: 75

GC03P037009
mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
(Previous names: mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2) )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbol: COCA2)
Services    

Aliases &
Descriptions
for MLH1

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc , and/or 7Ensembl, 8miRBase)
About This Section
Aliases
COCA2 2, 3, 5
FCC2 1, 2
HNPCC 1, 2
HNPCC2 1, 2, 5
MGC5172 2
hMLH1 2
Descriptions
DNA mismatch repair protein Mlh1 2
MutL protein homolog 1 2, 3
mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type
2) 1
mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) 2
External Ids
HGNC: 71271
Entrez Gene: 42922
UniProtKB: P406923
Ensembl: ENSG000000762427
Search outside databases for aliases for MLH1 gene

Previous GC identifers: GC03P036337 GC03P036848 GC03P036995

Summaries
for MLH1

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

 EntrezGene summary for MLH1:
This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer
(HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the
characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC.
Alternatively spliced transcript variants encoding different isoforms have been described, but
their full-length natures have not been determined. [provided by RefSeq]

UniProtKB/Swiss-Prot: MLH1_HUMAN, P40692
Function: Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA
mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta
(MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient
to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch
and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the
mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated
DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp
loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA
polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which
induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes
with MLH3 to form MutL gamma which plays a role in meiosis

Gene Wiki entry for MLH1

Genomic Location
for MLH1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

 Genomic View:
UCSC Golden Path with GeneCards custom track

 Transcription factor binding sites upstream to the MLH1 gene  

Entrez Gene cytogenetic band: 3p21.3   Ensembl cytogenetic band:  3p22.2   HGNC cytogenetic band: 3p22.3

MLH1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03P037009:     (about GC identifiers)

Start:
 37,009,983 bp from pter
End:
 37,067,341 bp from pter
Size:
 57,359 bases
Orientation:
 plus strand
RefSeq DNA sequence:
NC_000003.10  NT_022517.17  

Proteins
for MLH1

(According to 1UniProtKB, and/or Ensembl, Phosphorylation sites according to 2Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
About This Section

 UniProtKB/Swiss-Prot: MLH1_HUMAN, P40692 (See protein sequence)
Recommended Name: DNA mismatch repair protein Mlh1  
Size: 756 amino acids; 84601 Da
Subunit: Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3
(MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). 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 MBD4.
Interacts with EXO1
Subcellular location: Nucleus

Post-translational modifications:

  • View phosphorylation sites using PhosphoSite2


    • REFSEQ proteins: NP_000240.1  

    ENSEMBL proteins: 
    ENSP00000379724 ENSP00000231790 ENSP00000379715 ENSP00000373270 


    Human Recombinant Proteins 
    Browse Drug Discovery Central at Invitrogen for human recombinant proteins
    Browse Purified and Recombinant Proteins at Millipore
    Browse Human Recombinant Proteins at Sigma-Aldrich  
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Recombinant Proteins from Abcam (MLH1)
    Human Recombinant Proteins from Abnova (MLH1)
                  OriGene Purified Recombinant Human Protein: MLH1 

    1 Gene Ontology (GO) cellular component term (links to tree view):

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634 nucleus IC11809883
    About this table

    Antibodies for MLH1: 
    Invitrogen Antibodies for MLH1
    Millipore Mono- and Polyclonal Antibodies for the study of MLH1
    Sigma-Aldrich Antibodies for MLH1
    Browse R&D Systems for Antibodies
    Cell Signaling Technology (CST) Antibodies for MLH1 
    Antibodies from Abcam (MLH1), each with their AbpromiseSM
    Monoclonal and Polyclonal Antibodies from Abnova (MLH1)
    Novus Biologicals Antibodies for MLH1

    Assays for MLH1: 
    Browse Invitrogen for biochemical assays
    Millipore Kits and Assays for the Analysis of MLH1
    Browse R&D Systems for biochemical assays
    Browse biochemical assays available from Enzo Life Sciences

    Protein Domains/
    Families
    for MLH1

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/7 InterPro domains/families (see all 7 ):
     IPR011186 DNA_mismatch_repair_MLH1
     IPR003594 ATP_bd_ATPase
     IPR014762 DNA_mismatch_repair_CS
     IPR013507 DNA_mismatch_repair_C
     IPR014763 DNA_mismatch_repair_N


       GeneDecks  MLH1 for the domains selected above  
    About GeneDecksing

    Graphical View of Domain Structure for InterPro Entry P40692

    ProtoNet protein and cluster: P40692

    1 Blocks protein family: IPB002099 DNA mismatch repair protein

    UniProtKB/Swiss-Prot: MLH1_HUMAN, P40692
    Similarity: Belongs to the DNA mismatch repair mutL/hexB family

    Gene Function
    for MLH1

    (According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
    shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
    RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
    About This Section
    Inhib.
    RNA:    		Invitrogen RNAi Products for gene knock-down (MLH1)
    Browse for Gene Knock-down Tools from Millipore
    Abnova Chimera RNAi Products for Gene knock-down (MLH1)
                  OriGene 29mer shRNA kit in GFP-retroviral vector: NM_000249

                  Applied Biosystems Silencer® siRNAs for MLH1

                  Sigma-Aldrich siRNA and siRNA Panels for MLH1  
                         Sigma-Aldrich shRNA Panels and shRNA for MLH1  
                         Explore Sigma-Aldrich super-pooled esiRNAs  

    Clones:Invitrogen Clones for MLH1
    Browse Clones for the Expression of Recombinant Proteins Available from Millipore
                  OriGene GFP tagged cDNA clone in CMV expression vector: NM_000249
                                     Myc/DDK tagged cDNA clone in CMV expression vector: NM_000249
                                     untagged cDNA clones in CMV expression vector (see all 2): NM_000249 

    Primers: Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers
                  OriGene genome-wide validated SYBR primer pairs: NM_000249

    UniProtKB/Swiss-Prot: MLH1_HUMAN, P40692
    Function: Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA
    mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta
    (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
    Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient
    to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch
    and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the
    mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated
    DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp
    loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA
    polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which
    induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes
    with MLH3 to form MutL gamma which plays a role in meiosis

    Genatlas biochemistry entry for MLH1:
    yeast mutator gene homolog (bacterial mutL),with several spliced isoforms,involved in mismatch
    repair in non-small cell lung cancer (see TSG3B),deleted in sporadic colorectal cancer or mutated
    with hypermethylation of the promoter region,in breast cancer and in sporadic endometrial
    cancer,interacting with NF1 (predisposition to early hematological malignancy) and with PMS2

    7 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Mlh1):

    cellularendocrine/exocrine glandhomeostasis/metabolismlife span-post-weaning/agingreproductive system
    skin/coat/nailstumorigenesis

    5 Gene Ontology (GO) molecular function terms (links to tree view):

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003697contributes to single-stranded DNA binding IDA11809883
    GO:0005515 protein binding IPI2414623 11427529 11429708 14676842 17715146
    GO:0005524 ATP binding IEA--
    GO:0030983 mismatched DNA binding IEA--
    GO:0032407contributes to MutSalpha complex binding IDA16403449
    About this table

    Pathways & Interactions
    for MLH1

    (Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
    Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to 1UniProtKB, 2MINT, and/or 3STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
    About This Section

    1 Invitrogen iPath™ Online BioAtlas - Pathway for MLH1 (Maps provided by GeneGo):
     Role of Brca1 and Brca2 in DNA repair

       GeneDecks  MLH1 for the pathways selected above  
    About GeneDecksing

    1 Millipore Pathway for MLH1
     DNA damage Role of Brca1 and Brca2 in DNA repair

       GeneDecks  MLH1 for the pathways selected above  
    About GeneDecksing

    2 Sigma-Aldrich "Your Favorite Gene" Pathways for  MLH1  (Your Favorite Gene powered by Ingenuity) 
     Endometrial Cancer Signaling
     Role of BRCA1 in DNA Damage Response

       GeneDecks  MLH1 for the pathways selected above  
    About GeneDecksing

    4 Kegg Pathways  (Kegg details for MLH1):
     hsa03430 Mismatch repair
     hsa05200 Pathways in cancer
     hsa05210 Colorectal cancer
     hsa05213 Endometrial cancer

       GeneDecks  MLH1 for the pathways selected above  
    About GeneDecksing
     Gene Network CentralTM Interacting Genes and Proteins Network for  MLH1 


    5/102 Interacting proteins for MLH1 (ENSP000002317903 P406921, 2) via UniProtKB, MINT, and/or STRING (see all 102 )
    InteractantInteraction Details
    GeneCardExternal ID(s)
    BRIP1Q9BX632STRING (score=.775) MINT-5115529 MINT-5115470 MINT-5115499 MINT-5115319 MINT-5115375 MINT-5115489 MINT-5115552 MINT-5115348 MINT-5115512 MINT-5115404 MINT-5115429
    BRCA1P383982STRING (score=.984) MINT-5115348 MINT-5115319 MINT-5115375 MINT-5115552
    PMS2P542781, 2STRING (score=.999) EBI-744248, EBI-1162561 MINT-5115348 MINT-5115404 MINT-5115319 MINT-5115375 EBI-744248, EBI-1162561 MINT-5115348 MINT-5115404 MINT-5115319 MINT-5115375
    TMSB4XP623281EBI-744248, EBI-712598
    PMS2P542781, 2STRING (score=.999) EBI-744248, EBI-1162561 MINT-5115348 MINT-5115404 MINT-5115319 MINT-5115375 EBI-744248, EBI-1162561 MINT-5115348 MINT-5115404 MINT-5115319 MINT-5115375
    About this table

    3 Gene Ontology (GO) biological process terms (links to tree view):

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006298 mismatch repair TAS8128251
    GO:0006974 response to DNA damage stimulus IEA--
    GO:0045786 negative regulation of cell cycle IEA--
    About this table

    Drugs & Compounds
    for MLH1

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
    About This Section

    Browse drugs & compounds from Enzo Life Sciences
    Browse Small Molecules at Sigma-Aldrich

    Browse Tocris compounds for MLH1
    10/31 Novoseek chemical compound relationships for MLH1 gene (see all 31 )
    Compound   Score   Articles   PubMed IDs for Articles with Shared Sentences (# sentences)
    crcs 84.79 31 15294875 (3), 18257912 (3), 15749592 (2), 18618713 (2) (see all 17)
    mononucleotide 84.50 19 17504984 (2), 10675487 (1), 12479849 (1), 10674020 (1) (see all 17)
    mhs-2 74.53 2 9616736 (1), 7576988 (1)
    o6-methylguanine 61.55 14 17276933 (2), 16436636 (1), 19047896 (1), 14633667 (1) (see all 13)
    mnng 43.38 15 9750018 (4), 7641183 (3), 8044777 (1), 16085492 (1)
    n-methyl-n'-nitrosourea 35.35 8 15870882 (2), 9233776 (1), 13679151 (1)
    cytosine 30.96 10 9041175 (2), 9811473 (1)
    5-methylcytosine 13.21 2 12154064 (1), 11751682 (1)
    tetrahydrofolate 6.84 3 16981189 (1)
    agarose 5.65 1 16620731 (1)
    About this table


    Transcripts
    for MLH1

    (GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView,
    non coding RNAs according to RNAdb,
    ESTs according to GeneTide,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from Invitrogen, Millipore, and/or Abnova,
    siRNAs from Applied Biosystems, Sigma-Aldrich,
    shRNA from Sigma-Aldrich, OriGene,
    Tagged/untagged cDNA clones from OriGene,
    Expression Assays from Applied Biosystems)
    About This Section
    Inhib.
    RNA:    		Invitrogen RNAi Products for gene knock-down (MLH1)
    Browse for Gene Knock-down Tools from Millipore
    Abnova Chimera RNAi Products for Gene knock-down (MLH1)
                  OriGene 29mer shRNA kit in GFP-retroviral vector: NM_000249

                  Sigma-Aldrich siRNA and siRNA Panels for MLH1  
                         Sigma-Aldrich shRNA Panels and shRNA for MLH1  
                         Explore Sigma-Aldrich super-pooled esiRNAs  

    Applied Biosystems Silencer® siRNAs: 

    NM_000249  

    REFSEQ mRNAs for MLH1 gene: 

    NM_000249.2   

    Applied Biosystems TaqMan ® Gene Expression Assays: 

    NM_000249  

                  OriGene GFP tagged cDNA clone in CMV expression vector: NM_000249
                                     Myc/DDK tagged cDNA clone in CMV expression vector: NM_000249
                                     untagged cDNA clones in CMV expression vector (see all 2): NM_000249 

    Additional cDNA sequence: 

    AB209848.1 AK222810.1 AK295359.1 AK298324.1 AK298583.1 AK302807.1 AK311326.1 AK311365.1 
    AK312609.1 AK316074.1 AK316264.1 AY517558.1 BC006850.1 BX648844.1 CR609870.1 CR617505.1 
    DQ648888.1 DQ648889.1 DQ648890.1 DQ648891.1 DQ648892.1 DQ648893.1 EU188665.1 EU188666.1 
    EU188667.1 EU188668.1 EU188669.1 EU188670.1 EU188671.1 EU188672.1 EU188673.1 EU188674.1 
    EU188675.1 EU188676.1 U07343.1 U07418.1 

    20 DOTS entries:

    DT.445647  DT.100810259  DT.100810263  DT.95333713  DT.100810264  DT.101980402  DT.100028705  DT.100761169 
    DT.120922994  DT.92442427  DT.99999999  DT.120923036  DT.92442423  DT.97846810  DT.100760267  DT.100810256 
    DT.95156564  DT.100742075  DT.91798978  DT.99993535 

    24/278 AceView cDNA sequences (see all 278 ):

    BM697864 AL079560 AA318183 AU280370 AA343536 BU176348 CA307207 BI858386 
    CD644706 BI091720 BU737145 AI049637 BI090482 CN485008 CD106846 AU124504 
    BM452736 AI783880 BX098613 AI760156 BM709021 F08005 CA391710 BC006850 

    highest scoring ESTs for MLH1:

    U07418 AA069802 AA127766 AA146702 AA194918 AA216712 AA343535 AA347097 AA375419 AA385301 

    Unigene Cluster for MLH1:

    MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
    Hs.195364  [show with all ESTs]
    Unigene Representative Sequence: BX648844


    GeneLoc Exon Structure

    5/9 Alternative Splicing Database (ASD) splice patterns (SP) for MLH1 (see all 9 )

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b · 15c ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^
    SP1:                                                                                            -           -                                         -         
    SP2:              -           -                                                                 -           -                                         -         
    SP3:              -           -                                                                 -           -                                         -         
    SP4:                                                                                            -                                                               
    SP5:                                                                                      -     -     -     -                                                   

    ExUns: 20 ^ 21a · 21b ^ 22a · 22b
    SP1:                              
    SP2:                              
    SP3:  -     -     -               
    SP4:                              
    SP5:                              

    About this scheme

    ECgene alternative splicing isoforms for MLH1

    4 Ensembl transcripts including schematic representations:
    ENST00000396447  ENST00000231790  ENST00000396438  ENST00000383761  

    Expression
    for MLH1

    (Experimental results according to 1GeneNote and GNF BioGPS,
    probe sets-to-genes annotations according to 2GeneAnnot , 3GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
    Expression Assays from Applied Biosystems )
    About This Section

    MLH1 expression in normal and diseased human tissues

     Applied Biosystems TaqMan ® Gene Expression Assays for MLH1

    1 / 2 / 3

    4 probe-sets matching MLH1 gene


    		Affymetrix
    probe-set    		 Array  GeneAnnot data GeneNote data GeneTide data
    # genes Sensitivity Specificity Correlation Length Gb_Accession Consensus Uniqueness Score Rank

    		1850_at2, 3 U95-A 1 1.00 1.00 0.87 0.99 U07418 1.00 1.00 1.00 1

    		1944_f_at2, 3 U95-A 1 1.00 1.00 0.69 1.01 AF001359 0.40 1.00 0.76 1

    		202520_s_at2, 3 U133-A 1 1.00 1.00 -- -- NM_000249 0.60 1.00 0.82 1

    		202520_s_at2 U133Plus2 1 1.00 1.00 -- -- -- -- -- -- --
    About this table
    Data from (Publications) and GNF BioGPS
        About these images
    About these images

    CGAP SAGE TAG: CTTGCCTTAG

    SOURCE GeneReport for Unigene cluster: Hs.195364

    Expression variation in blood from EXPOLDB for MLH1

    UniProtKB/Swiss-Prot: MLH1_HUMAN, P40692
    Tissue specificity: Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall
    bladder and heart

    Orthologs
    for MLH1

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD and/or 5MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
    About This Section
    Orthologs for MLH1 gene from 5/19 species (see all 19 )
    Organism Gene Locus Description Human
    Similarity    		 NCBI accessions
    dog
    (Canis familiaris)    		 MLH11   -- mutL homolog 1, colon cancer, nonpolyposis type 2 (E. more 90.86(n)
    93.38(a)    		 477019  XM_534219.2  XP_534219.2 
    chimpanzee
    (Pan troglodytes)    		 MLH11   -- mutL homolog 1, colon cancer, nonpolyposis type 2 (E. more 99.74(n)
    99.6(a)    		 747104  XM_001170433.1  XP_001170433.1 
    cow
    (Bos taurus)    		 MLH11   -- mutL homolog 1, colon cancer, nonpolyposis type 2 (E. more 91.27(n)
    94.85(a)    		 533652  NM_001075994.1  NP_001069462.1 
    rat
    (Rattus norvegicus)    		 Mlh11   -- mutL homolog 1 (E. coli) 85.43(n)
    87.28(a)    		 81685  NM_031053.1  NP_112315.1 
    mouse
    (Mus musculus)    		 Mlh11, 5 9 (62.00 cM)5
    		 mutL homolog 1 (E. coli)1, 5 87.26(n)1
    88.62(a)1    		 173501  NM_026810.11  NP_081086.11 
     AA9206215  AF2508445  (see all 20)
    About this table        Species with no ortholog for MLH1

    ENSEMBL Gene Tree for MLH1

    Paralogs
    for MLH1

    (Paralogs according to 1HomoloGene
    and 2Ensembl, Pseudogenes according to 3Pseudogene.org)
    About This Section

    Paralogs for MLH1 gene
    MLH32  

    SNPs/Variants
    for MLH1

    (According to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
    About This Section


    10/685 NCBI SNPs in MLH1 are shown (see all 685 )
    (Click for Applied Biosystems TaqMan ® Genotyping Assay)  (see all 205)
    ABGenomic DataTranscription DataAllele Frequencies
    SNP IDValidChr 3 posSequenceRecsAA
    Chg    		TypeMoreRecsAllele
    freq    		PopTotal
    sample    		More
    ------------
    rs17999771,2
    		C,F,H,O37028572(+) GCTCCA/GTCTTT 1 I/V mis1 ese326Minor allele frequency- G:0.13MN NA CSAM EA NS EU WA 2534
    --
    rs20208731,2
    		C,F,H37067029(+) TGGAAC/TACATT 1 H/Y mis113Minor allele frequency- T:0.02NA EA MN EU WA 1362
    rs23083171,2
    		C,F,H37028554(+) CAACCG/ATGGAC 1 M/V mis1 ese316Minor allele frequency- A:0.01NA MN CSAM EA EU WA NS 1676
    --
    rs22348911,2
    		C,F37067313(+) GGATTGATT/-  
                ATAAA     		1 -- ut311Minor allele frequency- -:0.02NA 86
    --
    rs49869841,2
    		C,F37028566(+) ATATTC/TGCTCC 1 R/C mis16Minor allele frequency- T:0.01MN CSAM EA 428
    --
    rs115418591,2
    		H37017507(+) CCTTTG/CAGGAT 1 Q/E mis1 ese34Minor allele frequency- C:0.00EU EA WA 406
    rs46472561,2
    		A,C,F,H37025329(+) TACAAC/TATAGC 1 N/N syn1 ese318Minor allele frequency- T:0.02NS EU EA WA NA 1800
    rs18001461,2
    		C,F37065074(+) GGACTG/TCCTAT 1 L/L syn1 ese36Minor allele frequency- T:0.01NA MN CSAM EA 486
    rs18001441,2
    		C37020964(+) TGTGCA/GTACAG 1 A/A syn1 ese31Minor allele frequency- G:0.01NS 166
    rs46472201,2
    		H37017545(+) CGAGGT/GGAGGT 1 G/G syn15Minor allele frequency- G:0.00NS EU EA WA 594
    About this table

    HapMap Linkage Disequilibrium images for MLH1 (up to first 250kb)

    Disorders & Mutations
    for MLH1

    (in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
    About This Section

    		 OMIM: 120436   disorders: 609310  276300  158320  

    UniProtKB/Swiss-Prot: MLH1_HUMAN, P40692

  • Defects in MLH1 are the cause of hereditary non-polyposis colorectal cancer type 2
    (HNPCC2) [MIM:609310]. 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, and
    accounts for 15% of all colon cancers. 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.
    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
  • Defects in MLH1 are a cause of Turcot syndrome [MIM:276300]; also called mismatch repair
    cancer syndrome (MMRCS). Turcot syndrome 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
  • Defects in MLH1 are a cause of Muir-Torre syndrome (MTS) [MIM:158320]. MTS is a rare
    autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy
  • Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive
    neoplastic disease of the breast
  • Defects in MLH1 are a cause of susceptibility to endometrial cancer [MIM:608089]
  • Some epigenetic changes can be transmitted unchanged through the germline (termed
    'epigenetic inheritance'). Evidence that this mechanism occurs in humans is provided by the
    identification of individuals in whom 1 allele of the MLH1 gene is epigenetically silenced
    throughout the soma (implying a germline event). These individuals are affected by HNPCC but does
    not have identifiable mutations in MLH1, even though it is silenced, which demonstrats that an
    epimutation can phenocopy a genetic disease

    • 10/95 Novoseek disease relationships for MLH1 gene (see all 95 )

    Disease   Score   Articles   PubMed IDs for Articles with Shared Sentences (# sentences)
    microsatellite instability 98.05 493 16941012 (6), 11601928 (5), 11870540 (4), 16569647 (4) (see all 99)
    lynch syndrome 94.14 83 16143124 (4), 17973250 (3), 17278092 (3), 19424639 (3) (see all 51)
    colorectal cancer 94.04 1207 15294875 (8), 10922385 (8), 18547406 (7), 9399661 (6) (see all 99)
    hereditary nonpolyposis colon cancer 90.56 27 8895729 (2), 16736289 (2), 9927034 (2), 11179758 (2) (see all 23)
    germ-line mutation 85.45 70 11093816 (3), 18331697 (3), 9419403 (3), 9709044 (2) (see all 47)
    muir-torre syndrome 84.21 6 7616541 (1), 10815898 (1), 16826164 (1), 11859205 (1) (see all 6)
    colorectal carcinoma 83.19 95 10418831 (3), 12673483 (3), 15239345 (3), 9087566 (3) (see all 67)
    endometrial cancer 82.03 84 10938395 (4), 12700670 (3), 14760069 (3), 10072435 (3) (see all 51)
    colon cancer 78.97 108 11221878 (4), 11857087 (3), 15017620 (3), 15760919 (2) (see all 72)
    cancer 78.10 380 16106253 (6), 12861399 (4), 10861263 (4), 11496300 (3) (see all 99)
    About this table

    GeneTests: MLH1
    Hereditary Non-Polyposis Colon Cancer

    Human Gene Mutation Database: MLH1
    Genetic Association Database: MLH1
    Human Genome Epidemiology Navigator: MLH1 (154 documents)

    Medical News
    for MLH1

    (Possibly Related Articles in Doctor's Guide)
    About This Section

    Publications
    for MLH1

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

    		10/1489 PubMed articles for MLH1 gene (see all 1489 ):

    Search for MLH1

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section

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

    Genome Databases showing MLH1

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
    About This Section
    Entrez Gene: 4292 HGNC: 7127 AceView: MLH1 Ensembl:ENSG00000076242 euGenes: HUgn4292
    ECgene: MLH1 H-InvDB: MLH1

    Other Databases showing MLH1

    (According to HUGE)
    About This Section

    		   --

    Specialized Databases showing MLH1

    (According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    ATLAS Chromosomes in Cancer entry for MLH1 Genetics and Cytogenetics in Oncology and Haematology
    Hereditary non-polyposis colorectal cancer dbhttp://www.nfdht.nl/
    GeneReviewshttp://www.genetests.org/query?gene=MLH1
    NIEHS-SNPshttp://egp.gs.washington.edu/data/mlh1/

    Licensable Technologies
    for MLH1

    (Available from WIS Yeda, Salk, Tufts)
    About This Section

    		  --

    Services
    for MLH1

    (Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
    Sigma-Aldrich, R&D Systems, Millipore, Abnova, and/or Invitrogen, Clones available from OriGene,and/or Invitrogen, Drugs and/or compounds by Sigma-Aldrich,
    Enzo Life Sciences, and/or Tocris Bioscience)
    About This Section



    Products for MLH1:
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     shRNA in GFP-retroviral vector
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