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Aliases for MLH3 Gene

Aliases for MLH3 Gene

  • MutL Homolog 3 2 3 5
  • DNA Mismatch Repair Protein Mlh3 3
  • MutL (E. Coli) Homolog 3 2
  • MutL Homolog 3 (E. Coli) 2
  • MutL Protein Homolog 3 4
  • HNPCC7 3

External Ids for MLH3 Gene

Previous GeneCards Identifiers for MLH3 Gene

  • GC14M073009
  • GC14M069300
  • GC14M073473
  • GC14M074553
  • GC14M075481
  • GC14M055648

Summaries for MLH3 Gene

Entrez Gene Summary for MLH3 Gene

  • This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for MLH3 Gene

MLH3 (MutL Homolog 3) is a Protein Coding gene. Diseases associated with MLH3 include Colorectal Cancer, Hereditary Nonpolyposis, Type 7 and Endometrial Cancer. Among its related pathways are Cell Cycle, Mitotic and Meiosis. Gene Ontology (GO) annotations related to this gene include chromatin binding and single-stranded DNA binding.

UniProtKB/Swiss-Prot for MLH3 Gene

  • Probably involved in the repair of mismatches in DNA.

Gene Wiki entry for MLH3 Gene

Additional gene information for MLH3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MLH3 Gene

Genomics for MLH3 Gene

GeneHancer (GH) Regulatory Elements for MLH3 Gene

Promoters and enhancers for MLH3 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J075062 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 660.5 -12.4 -12393 2.1 PKNOX1 ATF1 ARID4B SIN3A DMAP1 ZNF48 POLR2B GLIS2 ELK1 ZNF143 MLH3 ACYP1 ZC2HC1C EIF2B2 NEK9 FCF1 YLPM1 PGF GC14M075064
GH14J075048 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 650.7 +1.1 1099 3.3 SIN3A DMAP1 YBX1 ZBTB7B ZNF48 SLC30A9 POLR2B ZNF766 ELK1 ZNF207 MLH3 NEK9 ACYP1 RNU6-689P
GH14J074083 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 25.4 +966.6 966621 3.5 HDGF PKNOX1 CLOCK FOXA2 SMAD1 ARNT ARID4B NEUROD1 SIN3A DMAP1 LIN52 PIR52311 ALDH6A1 ZNF410 LOC100506476 ELMSAN1 MLH3 YLPM1 FCF1 PTGR2
GH14J074610 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 18.7 +434.9 434948 11.8 ARNT ARID4B SIN3A DMAP1 ZBTB7B YY1 ZNF143 FOS SP3 REST LTBP2 ENSG00000258976 ELMSAN1 ZNF410 MLH3 YLPM1 ABCD4 ENSG00000258559 FCF1 ENSG00000222604
GH14J074140 Enhancer 1.4 FANTOM5 Ensembl ENCODE 35 +911.0 910960 0.8 PKNOX1 FEZF1 ZNF2 YY1 ZNF121 GLIS2 ZNF213 KLF7 SP3 RXRA LOC105370563 MLH3 YLPM1 ENSG00000258559 ABCD4 LIN52 ENSG00000259138 ELMSAN1 NEK9 ENSG00000258443
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MLH3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MLH3 gene promoter:
  • IRF-1
  • GR-beta
  • GR-alpha
  • GR
  • Arnt
  • c-Myb
  • c-Rel
  • FOXD1
  • Roaz

Genomic Locations for MLH3 Gene

Genomic Locations for MLH3 Gene
37,769 bases
Minus strand
37,769 bases
Minus strand

Genomic View for MLH3 Gene

Genes around MLH3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MLH3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MLH3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MLH3 Gene

Proteins for MLH3 Gene

  • Protein details for MLH3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    DNA mismatch repair protein Mlh3
    Protein Accession:
    Secondary Accessions:
    • P49751
    • Q56DK9
    • Q9P292
    • Q9UHC0

    Protein attributes for MLH3 Gene

    1453 amino acids
    Molecular mass:
    163711 Da
    Quaternary structure:
    • Heterodimer of MLH1 and MLH3. Interacts with MTMR15/FAN1.
    • Sequence=AAC42005.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305}; Sequence=AAC42005.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};

    Alternative splice isoforms for MLH3 Gene


neXtProt entry for MLH3 Gene

Post-translational modifications for MLH3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MLH3 Gene

Domains & Families for MLH3 Gene

Gene Families for MLH3 Gene

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

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the DNA mismatch repair MutL/HexB family.
  • Belongs to the DNA mismatch repair MutL/HexB family.
genes like me logo Genes that share domains with MLH3: view

Function for MLH3 Gene

Molecular function for MLH3 Gene

UniProtKB/Swiss-Prot Function:
Probably involved in the repair of mismatches in DNA.
GENATLAS Biochemistry:
yeast mutator gene homolog (bacterial Mut L),ubiquitously expressed,highly in gastrointestinal epithelium,interacting with MLH1,putatively primarily involved in repair of insestion/deletion loops and associated with microsatellite instability

Phenotypes From GWAS Catalog for MLH3 Gene

Gene Ontology (GO) - Molecular Function for MLH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IEA --
GO:0003696 satellite DNA binding TAS 10615123
GO:0003697 single-stranded DNA binding IBA --
GO:0005515 protein binding IPI 20603073
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with MLH3: view
genes like me logo Genes that share phenotypes with MLH3: view

Human Phenotype Ontology for MLH3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MLH3 Gene

MGI Knock Outs for MLH3:
  • Mlh3 Mlh3<tm1Lpkn>

Animal Model Products

miRNA for MLH3 Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for MLH3 Gene

Localization for MLH3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MLH3 Gene

Subcellular locations from

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 MLH3 gene
Compartment Confidence
nucleus 5
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MLH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000794 condensed nuclear chromosome IEA --
GO:0000795 synaptonemal complex IBA,IEA --
GO:0001673 male germ cell nucleus IEA --
GO:0005634 nucleus IDA,TAS --
GO:0005712 chiasma IEA,IBA --
genes like me logo Genes that share ontologies with MLH3: view

Pathways & Interactions for MLH3 Gene

genes like me logo Genes that share pathways with MLH3: view

Pathways by source for MLH3 Gene

3 Reactome pathways for MLH3 Gene
1 KEGG pathway for MLH3 Gene

Gene Ontology (GO) - Biological Process for MLH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IEA --
GO:0006298 mismatch repair NAS,IBA 12095912
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0007130 synaptonemal complex assembly IEA --
GO:0007131 reciprocal meiotic recombination NAS 12095912
genes like me logo Genes that share ontologies with MLH3: view

No data available for SIGNOR curated interactions for MLH3 Gene

Drugs & Compounds for MLH3 Gene

No Compound Related Data Available

Transcripts for MLH3 Gene

Unigene Clusters for MLH3 Gene

MutL homolog 3 (E. coli):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MLH3 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b
SP1: - -

Relevant External Links for MLH3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MLH3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MLH3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MLH3 Gene

This gene is overexpressed in Plasma (37.3), Seminal vesicle (20.4), and Rectum (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MLH3 Gene

NURSA nuclear receptor signaling pathways regulating expression of MLH3 Gene:


SOURCE GeneReport for Unigene cluster for MLH3 Gene:


mRNA Expression by UniProt/SwissProt for MLH3 Gene:

Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for MLH3 Gene

  • Nervous system(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MLH3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • nervous
  • reproductive
  • urinary
  • biliary tract
  • gallbladder
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
  • stomach
  • anus
  • ovary
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • uterus
  • blood
  • red blood cell
genes like me logo Genes that share expression patterns with MLH3: view

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for MLH3 Gene

Orthologs for MLH3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MLH3 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MLH3 34 33
  • 99.36 (n)
(Canis familiaris)
Mammalia MLH3 34 33
  • 86.66 (n)
(Bos Taurus)
Mammalia MLH3 34 33
  • 86.46 (n)
(Mus musculus)
Mammalia Mlh3 16 34 33
  • 81.05 (n)
(Rattus norvegicus)
Mammalia Mlh3 33
  • 80.22 (n)
(Ornithorhynchus anatinus)
Mammalia MLH3 34
  • 71 (a)
(Monodelphis domestica)
Mammalia MLH3 34
  • 59 (a)
(Gallus gallus)
Aves MLH3 34 33
  • 62.03 (n)
(Anolis carolinensis)
Reptilia MLH3 34
  • 48 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mlh3 33
  • 63.35 (n)
Str.7331 33
(Danio rerio)
Actinopterygii mlh3 34 33
  • 59.99 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MLH3 36 34 33
  • 42.99 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C10032g 33
  • 42.09 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AAL093C 33
  • 41.61 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 35 (a)
-- 34
  • 33 (a)
Species where no ortholog for MLH3 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • 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 (Oryza sativa)
  • 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MLH3 Gene

Gene Tree for MLH3 (if available)
Gene Tree for MLH3 (if available)
Evolutionary constrained regions (ECRs) for MLH3: view image

Paralogs for MLH3 Gene

(3) SIMAP similar genes for MLH3 Gene using alignment to 11 proteins:

  • B7Z5D1_HUMAN
  • G3V384_HUMAN
  • G3V3E0_HUMAN
  • G3V419_HUMAN
  • H0YJ15_HUMAN
  • Q2M1Z1_HUMAN
genes like me logo Genes that share paralogs with MLH3: view

No data available for Paralogs for MLH3 Gene

Variants for MLH3 Gene

Sequence variations from dbSNP and Humsavar for MLH3 Gene

SNP ID Clin Chr 14 pos Variation AA Info Type
rs10134636 likely-benign, Leukoencephalopathy with vanishing white matter, Lynch syndrome 75,014,117(-) G/A 3_prime_UTR_variant, genic_downstream_transcript_variant, non_coding_transcript_variant
rs1035991477 uncertain-significance, Lynch syndrome 75,016,193(-) C/T 3_prime_UTR_variant, downstream_transcript_variant, genic_downstream_transcript_variant, intron_variant
rs1039843487 uncertain-significance, MLH3-Related Lynch Syndrome 75,049,058(-) G/A coding_sequence_variant, non_coding_transcript_variant, stop_gained
rs1057518875 uncertain-significance, Breast carcinoma 75,046,622(-) C/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1060503068 uncertain-significance, MLH3-Related Lynch Syndrome 75,042,464(-) C/A coding_sequence_variant, missense_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for MLH3 Gene

Variant ID Type Subtype PubMed ID
esv1578153 CNV insertion 17803354
esv2489629 CNV insertion 19546169
nsv510644 CNV deletion 20534489

Variation tolerance for MLH3 Gene

Residual Variation Intolerance Score: 93.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.25; 85.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MLH3 Gene

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

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MLH3 Gene

Disorders for MLH3 Gene

MalaCards: The human disease database

(8) MalaCards diseases for MLH3 Gene - From: HGMD, OMIM, ClinVar, GTR, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
colorectal cancer, hereditary nonpolyposis, type 7
  • hnpcc7
endometrial cancer
  • endometrial cancer, familial
colorectal cancer
  • crc
colorectal cancer 7
  • colorectal cancer, susceptibility to, 7
lynch syndrome
  • colorectal cancer, hereditary nonpolyposis, type 1
- elite association - COSMIC cancer census association via MalaCards
Search MLH3 in MalaCards View complete list of genes associated with diseases


  • Hereditary non-polyposis colorectal cancer 7 (HNPCC7) [MIM:614385]: 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:11586295}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • 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:11317354}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for MLH3

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MLH3: view

No data available for Genatlas for MLH3 Gene

Publications for MLH3 Gene

  1. MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. (PMID: 10615123) Lipkin SM … Collins FS (Nature genetics 2000) 2 3 4 44 58
  2. Common germline variation in mismatch repair genes and survival after a diagnosis of colorectal cancer. (PMID: 19115210) Koessler T … Pharoah PD (International journal of cancer 2009) 3 22 44 58
  3. Common variants in mismatch repair genes and risk of colorectal cancer. (PMID: 18364438) Koessler T … Pharoah PD (Gut 2008) 3 22 44 58
  4. Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients. (PMID: 18723338) Mann A … Song H (European journal of cancer (Oxford, England : 1990) 2008) 3 22 44 58
  5. Common variants in mismatch repair genes and risk of invasive ovarian cancer. (PMID: 16774946) Song H … Gayther SA (Carcinogenesis 2006) 3 22 44 58

Products for MLH3 Gene

Sources for MLH3 Gene

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