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 inst... See more...

Aliases for MLH3 Gene

Aliases for MLH3 Gene

  • MutL Homolog 3 2 3 5
  • DNA Mismatch Repair Protein Mlh3 3 4
  • MutL (E. Coli) Homolog 3 2
  • MutL Homolog 3 (E. Coli) 2
  • MutL Protein Homolog 3 4
  • HNPCC7 3
  • MLH3 5

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 Meiosis and Mismatch repair. Gene Ontology (GO) annotations related to this gene include chromatin binding and single-stranded DNA binding. An important paralog of this gene is PMS1.

UniProtKB/Swiss-Prot Summary for MLH3 Gene

Gene Wiki entry for MLH3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MLH3 Gene

Genomics for MLH3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MLH3 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 MLH3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MLH3

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

Genomic Locations for MLH3 Gene

Genomic Locations for MLH3 Gene
chr14:75,013,764-75,051,532
(GRCh38/hg38)
Size:
37,769 bases
Orientation:
Minus strand
chr14:75,480,467-75,518,235
(GRCh37/hg19)
Size:
37,769 bases
Orientation:
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:
    Q9UHC1-MLH3_HUMAN
    Recommended name:
    DNA mismatch repair protein Mlh3
    Protein Accession:
    Q9UHC1
    Secondary Accessions:
    • P49751
    • Q56DK9
    • Q9P292
    • Q9UHC0

    Protein attributes for MLH3 Gene

    Size:
    1453 amino acids
    Molecular mass:
    163711 Da
    Quaternary structure:
    • Heterodimer of MLH1 and MLH3. Interacts with MTMR15/FAN1.
    SequenceCaution:
    • Sequence=AAC42005.1; Type=Frameshift; 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

    UniProtKB/Swiss-Prot:

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

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

Protein Domains for MLH3 Gene

Suggested Antigen Peptide Sequences for MLH3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ52020, highly similar to DNA mismatch repair protein Mlh3 (B7Z5D1_HUMAN)
  • MutL protein homolog 3 (MLH3_HUMAN)
  • MutL homolog 3 (E. coli), isoform CRA_c (Q2M1Z1_HUMAN)
  • MLH3 protein (Q6PIC9_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UHC1

UniProtKB/Swiss-Prot:

MLH3_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 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:0005515 protein binding IPI 11292842
GO:0005524 ATP binding IEA --
GO:0016887 ATPase activity IBA 21873635
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>
  • Mlh3 Mlh3<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MLH3

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

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 MLH3 gene
Compartment Confidence
nucleus 4
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 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: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 TAS 10615123
genes like me logo Genes that share ontologies with MLH3: view

Pathways & Interactions for MLH3 Gene

PathCards logo

SuperPathways 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 IBA,NAS 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

mRNA/cDNA for MLH3 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MLH3

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: - -
SP2:
SP3:

Relevant External Links for MLH3 Gene

GeneLoc Exon Structure for
MLH3

Expression for MLH3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MLH3

SOURCE GeneReport for Unigene cluster for MLH3 Gene:

Hs.436650

mRNA Expression by UniProt/SwissProt for MLH3 Gene:

Q9UHC1-MLH3_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for MLH3 Gene

  • Nervous system(4.6)
  • Intestine(2.5)
  • Blood(2.4)
  • Skin(2.1)
  • Stomach(2.1)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • nervous
  • reproductive
  • urinary
Regions:
Abdomen:
  • biliary tract
  • gallbladder
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • anus
  • ovary
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • uterus
General:
  • 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
Chimpanzee
(Pan troglodytes)
Mammalia MLH3 30 31
  • 99.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MLH3 30 31
  • 86.66 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MLH3 30 31
  • 86.46 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Mlh3 30 17 31
  • 81.05 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mlh3 30
  • 80.22 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia MLH3 31
  • 71 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MLH3 31
  • 59 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MLH3 30 31
  • 62.03 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MLH3 31
  • 48 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mlh3 30
  • 63.35 (n)
Str.7331 30
Zebrafish
(Danio rerio)
Actinopterygii mlh3 30 31
  • 59.99 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MLH3 30 31 33
  • 42.99 (n)
OneToOne
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C10032g 30
  • 42.09 (n)
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AAL093C 30
  • 41.61 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 35 (a)
OneToMany
-- 31
  • 33 (a)
OneToMany
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 Vase (Ciona intestinalis)
  • 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

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

Paralogs for MLH3 Gene

Paralogs for MLH3 Gene

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

  • MLH3_HUMAN
  • B7Z5D1_HUMAN
  • G3V384_HUMAN
  • G3V3E0_HUMAN
  • G3V419_HUMAN
  • H0YJ15_HUMAN
  • H0YJA3_HUMAN
  • H0YJB4_HUMAN
  • H0YJU3_HUMAN
  • Q2M1Z1_HUMAN
  • Q6PIC9_HUMAN
genes like me logo Genes that share paralogs with MLH3: view

Variants for MLH3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MLH3 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
641461 Uncertain Significance: MLH3-Related Lynch Syndrome 75,022,997(-) C/T MISSENSE_VARIANT
641949 Uncertain Significance: MLH3-Related Lynch Syndrome 75,047,006(-) C/T MISSENSE_VARIANT
642151 Uncertain Significance: MLH3-Related Lynch Syndrome 75,018,919(-) CAG/C FRAMESHIFT_VARIANT
642541 Uncertain Significance: MLH3-Related Lynch Syndrome 75,033,418(-) C/T INTRON_VARIANT
642836 Uncertain Significance: MLH3-Related Lynch Syndrome 75,049,420(-) T/C MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for MLH3 Gene

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)
MLH3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MLH3

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: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

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

UniProtKB/Swiss-Prot

MLH3_HUMAN
  • 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
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
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 41
  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 23 41
  3. Common variants in mismatch repair genes and risk of colorectal cancer. (PMID: 18364438) Koessler T … Pharoah PD (Gut 2008) 3 23 41
  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 23 41
  5. Common variants in mismatch repair genes and risk of invasive ovarian cancer. (PMID: 16774946) Song H … Gayther SA (Carcinogenesis 2006) 3 23 41

Products for MLH3 Gene

Sources for MLH3 Gene