MLH1 Gene (Protein Coding)

MutL Homolog 1

GC03P036993
GIFtS:
49
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 ... See more...

Aliases for MLH1 Gene

Aliases for MLH1 Gene

  • MutL Homolog 1 2 3 5
  • DNA Mismatch Repair Protein Mlh1 3 4
  • HNPCC2 2 3
  • COCA2 3 4
  • HNPCC 2 3
  • FCC2 2 3
  • 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
  • MutL Protein Homolog 1 4
  • MMRCS1 3
  • HMLH1 3
  • MLH1 5

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 Mismatch Repair Cancer Syndrome 1 and Muir-Torre Syndrome. Among its related pathways are Cell Cycle, Mitotic and DNA Double-Strand Break Repair. Gene Ontology (GO) annotations related to this gene include ATPase activity and mismatched DNA binding. An important paralog of this gene is MLH3.

UniProtKB/Swiss-Prot Summary 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-MSH3) 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 , Rfam classification and piRNA Summary for MLH1 Gene

Genomics for MLH1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for MLH1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MLH1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MLH1

Top Transcription factor binding sites by QIAGEN in the MLH1 gene promoter:
  • AP-2gamma
  • CREB
  • MRF-2
  • MyoD
  • Pax-6
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c

Genomic Locations for MLH1 Gene

Latest Assembly
chr3:36,993,350-37,050,846
(GRCh38/hg38)
Size:
57,497 bases
Orientation:
Plus strand

Previous Assembly
chr3:37,035,009-37,092,337
(GRCh37/hg19 by Entrez Gene)
Size:
57,329 bases
Orientation:
Plus strand

chr3:37,034,823-37,107,380
(GRCh37/hg19 by Ensembl)
Size:
72,558 bases
Orientation:
Plus strand

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

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  • 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:
    • Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). 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 (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10097147). Interacts with MCM9; the interaction recruits MLH1 to chromatin (PubMed:26300262). Interacts MCM8 (PubMed:26300262). Interacts with PMS2 (PubMed:11427529, PubMed:22753075). Interacts with MBD4 (PubMed:10097147). Interacts with EXO1 (PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842, PubMed:22753075). Interacts with MTMR15/FAN1 (PubMed:20603073).

    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

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MLH1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for MLH1

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:
  • DNA mismatch repair protein

Suggested Antigen Peptide Sequences for MLH1 Gene

GenScript: Design optimal peptide antigens:
  • Truncated mismatch repair protein MLH1 (A1YR10_HUMAN)
  • MutL homolog 1 protein (A5JTV0_HUMAN)
  • MutL homolog 1 protein (A5JTV1_HUMAN)
  • MutL-like 1 protein (A8W2I7_HUMAN)
  • MutL-like 1 protein (A8W2J0_HUMAN)

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

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  6. Cell Lines for research

Molecular function for MLH1 Gene

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-MSH3) 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:
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

Phenotypes From GWAS Catalog for MLH1 Gene

Gene Ontology (GO) - Molecular Function for MLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003682 chromatin binding IDA 26300262
GO:0003697 contributes_to single-stranded DNA binding IDA 11809883
GO:0005515 contributes_to protein binding IPI 16403449
GO:0005524 ATP binding IEA --
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:
  • Mlh1 Mlh1<tm1Mse>
  • Mlh1 Mlh1<tm1Rak>
  • Mlh1 Mlh1<tm1b(EUCOMM)Hmgu>
  • Mlh1 Mlh1<tm1Lisk>

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MLH1

Clone products for research

  • Addgene plasmids for MLH1

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

Localization for MLH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MLH1 Gene

Nucleus. Chromosome. Note=Recruited to chromatin in a MCM9-dependent manner. {ECO:0000269 PubMed:26300262}.

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 3
extracellular 2
cytoskeleton 2
mitochondrion 2
cytosol 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 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 IEA --
GO:0001673 male germ cell nucleus IEA --
GO:0005634 nucleus IC,IDA 26300262
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

3 BioSystems pathways for MLH1 Gene
1 GeneGo (Thomson Reuters) pathway for MLH1 Gene
  • DNA damage_Role of Brca1 and Brca2 in DNA repair
2 Qiagen pathways for MLH1 Gene
  • Colorectal Cancer Metastasis
  • Mismatch Repair in Eukaryotes
1 Cell Signaling Technology pathway for MLH1 Gene

SIGNOR curated interactions for MLH1 Gene

Is activated by:

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 IGI,TAS --
genes like me logo Genes that share ontologies with MLH1: view

Drugs & Compounds for MLH1 Gene

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(50) Drugs for MLH1 Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Aspirin Approved, Vet_approved Pharma 1600
Atorvastatin Approved Pharma 928
Analgesics Pharma 14477
Analgesics, Non-Narcotic Pharma 7760
Anticholesteremic Agents Pharma 2282

(30) 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

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mRNA/cDNA for MLH1 Gene

23 REFSEQ mRNAs :
39 NCBI additional mRNA sequence :
38 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MLH1

Clone products for research

  • 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

Expression for MLH1 Gene

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

mRNA expression in normal human tissues for MLH1 Gene
mRNA expression by GTEx for MLH1 GenemRNA expression by BioGPS 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, MaxQB, and MOPED for MLH1 Gene



Protein tissue co-expression partners for MLH1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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(4.9)
  • Kidney(4.6)
  • Liver(4.6)
  • Gall bladder(4.5)
  • Intestine(3.4)
  • Skin(3.2)
  • Stomach(2.9)
  • Lymph node(2.9)
  • Blood(2.8)
  • Thyroid gland(2.5)
  • Muscle(2.5)
  • Lung(2.4)
  • Heart(2.4)
  • Pancreas(2.3)
  • Spleen(2.3)
  • Bone marrow(2.2)

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

Primer products for research

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 29 30
  • 99.74 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia MLH1 29 30
  • 90.86 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia MLH1 29 30
  • 89.24 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Mlh1 29 16 30
  • 87.13 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Mlh1 29
  • 85.43 (n)
Oppossum
(Monodelphis domestica)
 Mammalia MLH1 30
  • 77 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia MLH1 30
  • 66 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves MLH1 29 30
  • 73.47 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia MLH1 30
  • 78 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia mlh1 29
  • 71.14 (n)
Str.16593 29
Zebrafish
(Danio rerio)
 Actinopterygii mlh1 29 30
  • 67.08 (n)
 OneToOne
zgc66301 29
Fruit Fly
(Drosophila melanogaster)
 Insecta Mlh1 29 30 31
  • 56.06 (n)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP012192 29
  • 55.09 (n)
Worm
(Caenorhabditis elegans)
 Secernentea mlh-1 30 31
  • 34 (a)
 OneToOne
K. Lactis Yeast
(Kluyveromyces lactis)
 Saccharomycetes KLLA0D09955g 29
  • 49.33 (n)
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes MLH1 29 30 32
  • 47.89 (n)
 OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
 Saccharomycetes AGOS_AFL199C 29
  • 47.46 (n)
Thale Cress
(Arabidopsis thaliana)
 eudicotyledons MLH1 29
  • 52.3 (n)
Rice
(Oryza sativa)
 Liliopsida Os01g0958900 29
  • 54.11 (n)
Os.10900 29
Bread mold
(Neurospora crassa)
 Ascomycetes NCU08309 29
  • 51.47 (n)
Fission Yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes mlh1 29
  • 49.09 (n)
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 30
  • 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 Vase (Ciona intestinalis)
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for MLH1: view image
Alliance of Genome Resources:
Additional Orthologs for MLH1

Paralogs for MLH1 Gene

Paralogs for MLH1 Gene

(4) SIMAP similar genes for MLH1 Gene using alignment to 37 proteins:

  • MLH1_HUMAN
  • A1YR10_HUMAN
  • A5JTV0_HUMAN
  • A5JTV1_HUMAN
  • A8W2I7_HUMAN
  • A8W2J0_HUMAN
  • A8W2J3_HUMAN
  • A8W2J6_HUMAN
  • A8W2J9_HUMAN
  • A8W2K2_HUMAN
  • A8W2K5_HUMAN
  • A8W2K8_HUMAN
  • A8W2L2_HUMAN
  • A8W2L5_HUMAN
  • A8W2L8_HUMAN
  • A8W2M1_HUMAN
  • B7Z821_HUMAN
  • C4PFY8_HUMAN
  • C9JZ54_HUMAN
  • E7EUC9_HUMAN
  • E9PF25_HUMAN
  • F2Z298_HUMAN
  • H0Y4N0_HUMAN
  • H0Y5L7_HUMAN
  • H0Y5U4_HUMAN
  • H0Y793_HUMAN
  • H0Y806_HUMAN
  • H0Y818_HUMAN
  • L8E8C0_HUMAN
  • Q0ZAJ3_HUMAN
  • Q0ZAJ4_HUMAN
  • Q0ZAJ5_HUMAN
  • Q0ZAJ6_HUMAN
  • Q0ZAJ7_HUMAN
  • Q0ZAJ8_HUMAN
  • Q64FK0_HUMAN
  • Q6VBB8_HUMAN
genes like me logo Genes that share paralogs with MLH1: view

Variants for MLH1 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MLH1 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
1000222 Uncertain Significance: Hereditary nonpolyposis colorectal neoplasms 37,048,583(+) A/T
NM_000249.4(MLH1):c.1963A>T (p.Ile655Phe) 		MISSENSE_VARIANT,INTRON
1001077 Uncertain Significance: Hereditary nonpolyposis colorectal neoplasms 37,042,318(+) T/C
NM_000249.4(MLH1):c.1718T>C (p.Val573Ala) 		MISSENSE
1001235 Uncertain Significance: Hereditary nonpolyposis colorectal neoplasms 37,011,854(+) G/A
NM_000249.4(MLH1):c.580G>A (p.Val194Ile) 		MISSENSE_VARIANT,FIVE_PRIME_UTR
1001928 Uncertain Significance: Hereditary nonpolyposis colorectal neoplasms 37,004,480(+) G/T
NM_000249.4(MLH1):c.380+6G>T 		INTRON
1003938 Uncertain Significance: Hereditary nonpolyposis colorectal neoplasms 37,014,443(+) A/G
NM_000249.4(MLH1):c.689A>G (p.Glu230Gly) 		MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MLH1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

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

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
Leiden Open Variation Database (LOVD)
MLH1

SNP Genotyping and Copy Number Assays for research

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

Disorders for MLH1 Gene

MalaCards: The human disease database

(121) MalaCards diseases for MLH1 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- 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
  • 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 variants 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 variants 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 variants 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.
  • 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 variants affecting the gene represented in this entry.
  • Note=Some