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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]
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.
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 Gastric cancer and Mismatch repair. Gene Ontology (GO) annotations related to this gene include ATPase activity and mismatched DNA binding. An important paralog of this gene is PMS2.
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 | -- |
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:0005623 | cell | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Mismatch repair |
.54
Mismatch Repair in Eukaryotes
.54
.01
|
.01
|
2 | Endometrial cancer | ||
3 | Gene Expression |
.48
|
|
4 | Meiosis |
.73
|
|
5 | DNA Damage |
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 | -- |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
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: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MLH1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | MLH1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | MLH1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Mlh1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Mlh1 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | MLH1 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MLH1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | MLH1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | MLH1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | mlh1 30 |
|
||
Str.16593 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | mlh1 30 31 |
|
OneToOne | |
zgc66301 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Mlh1 30 31 32 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP012192 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | mlh-1 31 32 |
|
OneToOne | |
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0D09955g 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | MLH1 30 31 33 |
|
OneToOne | |
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AFL199C 30 |
|
||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | MLH1 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os01g0958900 30 |
|
||
Os.10900 30 |
|
||||
Bread mold (Neurospora crassa) |
Ascomycetes | NCU08309 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | mlh1 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 03 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
455415 | Uncertain Significance: Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colon cancer; not specified; not provided | 37,048,994(+) | GA/TC | MISSENSE_VARIANT,INTRON_VARIANT | |
627657 | Likely Benign: Hereditary cancer-predisposing syndrome | 37,050,659(+) | GTTAT/G | THREE_PRIME_UTR_VARIANT | |
638664 | Likely Pathogenic: Lynch syndrome I | 37,050,617(+) | CCTGCCTGATCTA/C | INFRAME_DELETION | |
638829 | Uncertain Significance: Hereditary nonpolyposis colon cancer | 37,004,479(+) | A/G | INTRON_VARIANT | |
639057 | Pathogenic: Hereditary nonpolyposis colon cancer | 37,048,609(+) | G/C | MISSENSE_VARIANT,INTRON_VARIANT |
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 |