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MLH1 Gene(Protein Coding)

MutL Homolog 1

GCID:
GC03P036993
GIFtS:
57
Genes Participants
UDN Logo

Aliases for MLH1 Gene

Aliases for MLH1 Gene

  • MutL Homolog 1 2 3 5
  • COCA2 3 4
  • MutL (E. Coli) Homolog 1 (Colon Cancer, Nonpolyposis Type 2) 2
  • MutL Homolog 1, Colon Cancer, Nonpolyposis Type 2 (E. Coli) 2
  • MutL Homolog 1, Colon Cancer, Nonpolyposis Type 2 3
  • DNA Mismatch Repair Protein Mlh1 3
  • MutL Protein Homolog 1 4
  • HNPCC2 3
  • HNPCC 3
  • HMLH1 3
  • FCC2 3

External Ids for MLH1 Gene

Previous HGNC Symbols for MLH1 Gene

  • COCA2

Previous GeneCards Identifiers for MLH1 Gene

  • GC03P036337
  • GC03P036848
  • GC03P036995
  • GC03P037009
  • GC03P036976
  • GC03P037034

Summaries for MLH1 Gene

Entrez Gene Summary for MLH1 Gene

  • The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]

CIViC summary for MLH1 Gene

  • MLH1 is a tumor suppressor gene involved in DNA mismatch repair. Germline mutations in this gene are known to cause Lynch syndrome. The most common malignancies in Lynch syndrome are colorectal and endometrial carcinomas. In addition to germline mutations, somatic mutations in this gene have been described in colorectal and endometrial cancers.

GeneCards Summary for MLH1 Gene

MLH1 (MutL Homolog 1) is a Protein Coding gene. Diseases associated with MLH1 include Colorectal Cancer, Hereditary Nonpolyposis, Type 2 and Mismatch Repair Cancer Syndrome. Among its related pathways are Mismatch repair and Ovarian Infertility Genes. Gene Ontology (GO) annotations related to this gene include ATPase activity and mismatched DNA binding.

UniProtKB/Swiss-Prot for MLH1 Gene

  • 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 Gene

Additional gene information for MLH1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MLH1 Gene

Genomics for MLH1 Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for MLH1 Gene

Promoters and enhancers for MLH1 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH03I036988 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 558.2 -1.8 -1800 7.1 CLOCK ZFP64 DMAP1 IRF4 YY1 SLC30A9 E2F8 SP3 NFYC SSRP1 MLH1 EPM2AIP1 TRANK1 LRRFIP2 ENSG00000272334 RPS16P4 GC03P036930
GH03I037173 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 8.4 +182.5 182536 4.8 PKNOX1 SMAD1 FOXA2 ZFP64 ARID4B SIN3A FEZF1 DMAP1 ZNF2 IRF4 LRRFIP2 GC03P037179 UBE2FP1 RNU6-1301P RPS16P4 MLH1 C3orf35 DCLK3 TRANK1 GC03P036930
GH03I036968 Enhancer 1.4 FANTOM5 Ensembl ENCODE 13.7 -23.4 -23437 2.3 HDGF PKNOX1 ATF1 ARNT IRF4 TCF12 ZNF766 CBX5 GATA2 FOS GC03M036968 GC03M036969 RNU6ATAC4P LRRFIP2 EPM2AIP1 MLH1 TRANK1 GOLGA4 ITGA9 ENSG00000272334
GH03I036890 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 12.5 -99.7 -99655 5.4 HDAC1 PKNOX1 ATF1 RB1 BMI1 YBX1 BATF ZBTB40 CBX5 ZNF143 MLH1 EPM2AIP1 TRANK1 ENSG00000234073 DCLK3 GC03M036882
GH03I036900 Enhancer 1 FANTOM5 ENCODE dbSUPER 11.1 -92.1 -92064 1.8 SMARCE1 MEIS2 PKNOX1 ADNP ZMYM3 ZNF384 ATF2 GC03M036882 TRANK1 RNU6ATAC4P EPM2AIP1 MLH1 ENSG00000234073 GOLGA4 GC03P036930
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MLH1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MLH1 gene promoter:

Genomic Locations for MLH1 Gene

Genomic Locations for MLH1 Gene
chr3:36,993,332-37,050,918
(GRCh38/hg38)
Size:
57,587 bases
Orientation:
Plus strand
chr3:37,034,823-37,107,380
(GRCh37/hg19)

Genomic View for MLH1 Gene

Genes around MLH1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MLH1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MLH1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for MLH1 Gene

Proteins for MLH1 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for MLH1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P40692-MLH1_HUMAN
    Recommended name:
    DNA mismatch repair protein Mlh1
    Protein Accession:
    P40692
    Secondary Accessions:
    • B4DI13
    • B4DQ11
    • E9PCU2

    Protein attributes for MLH1 Gene

    Size:
    756 amino acids
    Molecular mass:
    84601 Da
    Quaternary structure:
    • 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 and MTMR15/FAN1.

    Three dimensional structures from OCA and Proteopedia for MLH1 Gene

    Alternative splice isoforms for MLH1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MLH1 Gene

Protein Expression for MLH1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for MLH1 Gene

No Post-translational modifications

Other Protein References for MLH1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for MLH1 Gene

Domains & Families for MLH1 Gene

Gene Families for MLH1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for MLH1 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for MLH1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P40692

UniProtKB/Swiss-Prot:

MLH1_HUMAN :
  • Belongs to the DNA mismatch repair MutL/HexB family.
Family:
  • Belongs to the DNA mismatch repair MutL/HexB family.
genes like me logo Genes that share domains with MLH1: view

Function for MLH1 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for MLH1 Gene

GENATLAS Biochemistry:
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
UniProtKB/Swiss-Prot 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 Ontology (GO) - Molecular Function for MLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IEA --
GO:0003697 contributes_to single-stranded DNA binding IDA 11809883
GO:0005515 contributes_to protein binding IPI 16403449
GO:0005524 ATP binding IEA --
GO:0016887 ATPase activity IBA --
genes like me logo Genes that share ontologies with MLH1: view
genes like me logo Genes that share phenotypes with MLH1: view

Human Phenotype Ontology for MLH1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MLH1 Gene

MGI Knock Outs for MLH1:

Animal Model Products

Clone Products

  • Addgene plasmids for MLH1

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for MLH1 Gene

Localization for MLH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MLH1 Gene

Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MLH1 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 1
cytoskeleton 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000793 condensed chromosome IEA --
GO:0000794 condensed nuclear chromosome IEA --
GO:0000795 synaptonemal complex IBA --
GO:0001673 male germ cell nucleus IEA --
GO:0005634 nucleus IC 11809883
genes like me logo Genes that share ontologies with MLH1: view

Pathways & Interactions for MLH1 Gene

genes like me logo Genes that share pathways with MLH1: view

Pathways by source for MLH1 Gene

1 Cell Signaling Technology pathway for MLH1 Gene
3 BioSystems pathways for MLH1 Gene
1 GeneGo (Thomson Reuters) pathway for MLH1 Gene

Gene Ontology (GO) - Biological Process for MLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening IEA --
GO:0000712 resolution of meiotic recombination intermediates IEA --
GO:0002204 somatic recombination of immunoglobulin genes involved in immune response IEA --
GO:0006281 DNA repair IEA --
GO:0006298 mismatch repair TAS,IGI --
genes like me logo Genes that share ontologies with MLH1: view

No data available for SIGNOR curated interactions for MLH1 Gene

Drugs & Compounds for MLH1 Gene

Products:

  1. Drug

(34) Drugs for MLH1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(31) Additional Compounds for MLH1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with MLH1: view

Transcripts for MLH1 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for MLH1 Gene

(31) REFSEQ mRNAs :
(34) Additional mRNA sequences :
(278) Selected AceView cDNA sequences:
(23) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for MLH1 Gene

MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli):
Representative Sequences:

Clone Products

  • Addgene plasmids for MLH1

Alternative Splicing Database (ASD) splice patterns (SP) for MLH1 Gene

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: - - - -
SP6: -
SP7:
SP8:
SP9: -

ExUns: 20 ^ 21a · 21b ^ 22a · 22b
SP1:
SP2:
SP3: - - -
SP4:
SP5:
SP6:
SP7:
SP8: -
SP9:

Relevant External Links for MLH1 Gene

GeneLoc Exon Structure for
MLH1
ECgene alternative splicing isoforms for
MLH1

Expression for MLH1 Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MLH1 Gene

mRNA expression in normal human tissues for MLH1 Gene
mRNA expression by BioGPS for MLH1 GenemRNA expression by GTEx for MLH1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MLH1 Gene

This gene is overexpressed in Testis (11.1), Plasma (10.9), and Fetal ovary (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MLH1 Gene



Protein tissue co-expression partners for MLH1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MLH1 Gene:

MLH1

SOURCE GeneReport for Unigene cluster for MLH1 Gene:

Hs.195364

mRNA Expression by UniProt/SwissProt for MLH1 Gene:

P40692-MLH1_HUMAN
Tissue specificity: Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.

Evidence on tissue expression from TISSUES for MLH1 Gene

  • Nervous system(4.8)
  • Kidney(4.5)
  • Gall bladder(4.4)
  • Liver(4.4)
  • Intestine(3.7)
  • Skin(2.8)
  • Stomach(2.7)
  • Lymph node(2.6)
  • Blood(2.4)
  • Lung(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MLH1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • epiglottis
  • eye
  • eyelid
  • face
  • head
  • larynx
  • meninges
  • neck
  • skull
  • vocal cord
Thorax:
  • breast
  • esophagus
  • trachea
Abdomen:
  • adrenal gland
  • biliary tract
  • duodenum
  • gallbladder
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • anus
  • ovary
  • pelvis
  • penis
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • uterus
Limb:
  • arm
  • upper limb
General:
  • blood
  • bone marrow
  • red blood cell
  • skin
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with MLH1: view

No data available for mRNA differential expression in normal tissues for MLH1 Gene

Orthologs for MLH1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MLH1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia MLH1 33 34
  • 99.74 (n)
dog
(Canis familiaris)
 Mammalia MLH1 33 34
  • 90.86 (n)
cow
(Bos Taurus)
 Mammalia MLH1 33 34
  • 89.24 (n)
mouse
(Mus musculus)
 Mammalia Mlh1 33 16 34
  • 87.13 (n)
rat
(Rattus norvegicus)
 Mammalia Mlh1 33
  • 85.43 (n)
oppossum
(Monodelphis domestica)
 Mammalia MLH1 34
  • 77 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia MLH1 34
  • 66 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves MLH1 33 34
  • 73.47 (n)
lizard
(Anolis carolinensis)
 Reptilia MLH1 34
  • 78 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia mlh1 33
  • 71.14 (n)
Str.16593 33
zebrafish
(Danio rerio)
 Actinopterygii mlh1 33 34
  • 67.08 (n)
zgc66301 33
fruit fly
(Drosophila melanogaster)
 Insecta Mlh1 35 33 34
  • 56.06 (n)
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP012192 33
  • 55.09 (n)
worm
(Caenorhabditis elegans)
 Secernentea mlh-1 35 34
  • 32 (a)
K. lactis yeast
(Kluyveromyces lactis)
 Saccharomycetes KLLA0D09955g 33
  • 49.33 (n)
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes MLH1 33 34 36
  • 47.89 (n)
A. gosspyii yeast
(Ashbya gossypii)
 Saccharomycetes AGOS_AFL199C 33
  • 47.46 (n)
thale cress
(Arabidopsis thaliana)
 eudicotyledons MLH1 33
  • 52.3 (n)
rice
(Oryza sativa)
 Liliopsida Os01g0958900 33
  • 54.11 (n)
Os.10900 33
bread mold
(Neurospora crassa)
 Ascomycetes NCU08309 33
  • 51.47 (n)
fission yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes mlh1 33
  • 49.09 (n)
sea squirt
(Ciona savignyi)
 Ascidiacea -- 34
  • 48 (a)
 OneToOne
Species where no ortholog for MLH1 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MLH1 Gene

ENSEMBL:
Gene Tree for MLH1 (if available)
TreeFam:
Gene Tree for MLH1 (if available)

Paralogs for MLH1 Gene

No data available for Paralogs for MLH1 Gene

Variants for MLH1 Gene

Sequence variations from dbSNP and Humsavar for MLH1 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1017112753 likely-benign, not specified, Hereditary nonpolyposis colon cancer 37,012,003(+) T/C intron_variant
rs1044486319 uncertain-significance, Hereditary cancer-predisposing syndrome, not specified 37,050,601(+) T/A/C coding_sequence_variant, missense_variant
rs1046979393 uncertain-significance, Lynch syndrome 37,040,263(+) A/G coding_sequence_variant, missense_variant
rs104894994 uncertain-significance, not-provided, not specified, Lynch syndrome, not provided 36,993,541(+) C/A/T 5_prime_UTR_variant, genic_upstream_transcript_variant, upstream_transcript_variant
rs104894997 uncertain-significance, not-provided, Lynch syndrome, not provided, Hereditary nonpolyposis colon cancer, Hereditary cancer-predisposing syndrome 37,014,542(+) A/C/G 5_prime_UTR_variant, coding_sequence_variant, intron_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for MLH1 Gene

Variant ID Type Subtype PubMed ID
nsv967004 CNV duplication 23825009
nsv954463 CNV duplication 24416366
nsv834663 CNV loss 17160897
nsv834662 CNV loss 17160897
nsv1109507 CNV deletion 24896259
esv3595878 CNV loss 21293372
esv3568690 CNV loss 25503493
esv1133148 CNV deletion 17803354

Variation tolerance for MLH1 Gene

Residual Variation Intolerance Score: 40.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.63; 82.76% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MLH1 Gene

Human Gene Mutation Database (HGMD)
MLH1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MLH1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MLH1 Gene

Disorders for MLH1 Gene

MalaCards: The human disease database

(63) MalaCards diseases for MLH1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search MLH1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MLH1_HUMAN
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269 PubMed:10598809, ECO:0000269 PubMed:10882759, ECO:0000269 PubMed:12132870, ECO:0000269 PubMed:12655564, ECO:0000269 PubMed:14504054, ECO:0000269 PubMed:15184898, ECO:0000269 PubMed:18033691, ECO:0000269 PubMed:8872463, ECO:0000269 PubMed:9032648, ECO:0000269 PubMed:9087566, ECO:0000269 PubMed:9611074}. Note=Disease susceptibility is associated with variations 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.
  • Hereditary non-polyposis colorectal cancer 2 (HNPCC2) [MIM:609310]: 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. {ECO:0000269 PubMed:10323887, ECO:0000269 PubMed:10375096, ECO:0000269 PubMed:10386556, ECO:0000269 PubMed:10413423, ECO:0000269 PubMed:10480359, ECO:0000269 PubMed:10598809, ECO:0000269 PubMed:10627141, ECO:0000269 PubMed:10660333, ECO:0000269 PubMed:10671064, ECO:0000269 PubMed:10713887, ECO:0000269 PubMed:10777691, ECO:0000269 PubMed:10882759, ECO:0000269 PubMed:11139242, ECO:0000269 PubMed:11427529, ECO:0000269 PubMed:11726306, ECO:0000269 PubMed:11748856, ECO:0000269 PubMed:11754112, ECO:0000269 PubMed:11781295, ECO:0000269 PubMed:11793442, ECO:0000269 PubMed:11839723, ECO:0000269 PubMed:11870161, ECO:0000269 PubMed:12095971, ECO:0000269 PubMed:12132870, ECO:0000269 PubMed:12200596, ECO:0000269 PubMed:12362047, ECO:0000269 PubMed:12373605, ECO:0000269 PubMed:12655562, ECO:0000269 PubMed:12658575, ECO:0000269 PubMed:14635101, ECO:0000269 PubMed:14961575, ECO:0000269 PubMed:15064764, ECO:0000269 PubMed:15139004, ECO:0000269 PubMed:15365995, ECO:0000269 PubMed:15365996, ECO:0000269 PubMed:16083711, ECO:0000269 PubMed:16451135, ECO:0000269 PubMed:17301300, ECO:0000269 PubMed:17510385, ECO:0000269 PubMed:18561205, ECO:0000269 PubMed:20020535, ECO:0000269 PubMed:21120944, ECO:0000269 PubMed:22753075, ECO:0000269 PubMed:7757073, ECO:0000269 PubMed:8566964, ECO:0000269 PubMed:8571956, ECO:0000269 PubMed:8797773, ECO:0000269 PubMed:8872463, ECO:0000269 PubMed:8993976, ECO:0000269 PubMed:9048925, ECO:0000269 PubMed:9067757, ECO:0000269 PubMed:9218993, ECO:0000269 PubMed:9272156, ECO:0000269 PubMed:9298827, ECO:0000269 PubMed:9311737, ECO:0000269 PubMed:9326924, ECO:0000269 PubMed:9399661, ECO:0000269 PubMed:9559627, ECO:0000269 PubMed:9718327, ECO:0000269 PubMed:9833759, ECO:0000269 PubMed:9927034, ECO:0000269 Ref.5}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients. {ECO:0000269 PubMed:11427529, ECO:0000269 PubMed:17440981, ECO:0000269 PubMed:7661930}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. {ECO:0000269 PubMed:8751876}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast.
  • Note=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 demonstrates that an epimutation can phenocopy a genetic disease.

Additional Disease Information for MLH1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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No data available for Genatlas for MLH1 Gene

Publications for MLH1 Gene

  1. I219V polymorphism in hMLH1 gene in patients affected with ulcerative colitis. (PMID: 19371218) Vietri MT … Cioffi M (Genetic testing and molecular biomarkers 2009) 3 22 44 58
  2. Effect of DNA repair host factors on temozolomide or dacarbazine melanoma treatment in Caucasians. (PMID: 19741564) Boeckmann L … Emmert S (Pharmacogenetics and genomics 2009) 3 22 44 58
  3. Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. (PMID: 19858398) Braun MS … Seymour MT (Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009) 3 22 44 58
  4. Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. (PMID: 18033691) Barnetson RA … Dunlop MG (Human mutation 2008) 3 4 44 58
  5. Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma. (PMID: 18199718) Wang J … Xu B (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2008) 3 22 44 58

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