Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA mismatch repair protein Mlh1

Gene

MLH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywordsi

Biological processCell cycle, DNA damage, DNA repair

Enzyme and pathway databases

BioCyciZFISH:ENSG00000076242-MONOMER.
ReactomeiR-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-HSA-912446. Meiotic recombination.
SIGNORiP40692.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Mlh1
Alternative name(s):
MutL protein homolog 1
Gene namesi
Name:MLH1
Synonyms:COCA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:7127. MLH1.

Subcellular locationi

GO - Cellular componenti

  • chiasma Source: GO_Central
  • male germ cell nucleus Source: Ensembl
  • membrane Source: UniProtKB
  • MutLalpha complex Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: HGNC
  • synaptonemal complex Source: GO_Central

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 2 (HNPCC2)58 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:609310
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02266318R → C in HNPCC2. Corresponds to variant dbSNP:rs3676545521 PublicationEnsembl.1
Natural variantiVAR_04338319I → F in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637506481 PublicationEnsembl.1
Natural variantiVAR_04338421A → V in HNPCC2. Corresponds to variant dbSNP:rs637507061 PublicationEnsembl.1
Natural variantiVAR_04338525I → F in HNPCC2. Corresponds to variant dbSNP:rs637498381 PublicationEnsembl.1
Natural variantiVAR_00443328P → L in HNPCC2; loss of protein expression; normal interaction with PMS2 and EXO1; decreased mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs637507927 PublicationsEnsembl.1
Natural variantiVAR_04338629A → S in HNPCC2; unknown pathological significance; acts functionally like the wild-type protein. Corresponds to variant dbSNP:rs637506563 PublicationsEnsembl.1
Natural variantiVAR_07633831A → C in HNPCC2; requires 2 nucleotide substitutions; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637499941 PublicationEnsembl.1
Natural variantiVAR_04338735M → K in HNPCC2; unknown pathological significance. 1 Publication1
Natural variantiVAR_00443435M → R in HNPCC2. Corresponds to variant dbSNP:rs63749906Ensembl.1
Natural variantiVAR_07633937E → K in HNPCC2; decreased mismatch repair activity; loss of nuclear localization. Corresponds to variant dbSNP:rs637510122 PublicationsEnsembl.1
Natural variantiVAR_04338938N → H in HNPCC2; decreased mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs637505803 PublicationsEnsembl.1
Natural variantiVAR_07634038N → K in HNPCC2; decreased mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs2676077062 PublicationsEnsembl.1
Natural variantiVAR_04339041D → G in HNPCC2. Corresponds to variant dbSNP:rs637510941 PublicationEnsembl.1
Natural variantiVAR_05452241D → H Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676077131 PublicationEnsembl.1
Natural variantiVAR_00443644S → F in HNPCC2; no effect on MLH1 splicing; loss of mismatch repair activity. Corresponds to variant dbSNP:rs637511093 PublicationsEnsembl.1
Natural variantiVAR_04339145 – 47TSI → CF in HNPCC2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. 1 Publication3
Natural variantiVAR_00443762Q → K in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637514281 PublicationEnsembl.1
Natural variantiVAR_04339263D → E in HNPCC2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. Corresponds to variant dbSNP:rs5877789552 PublicationsEnsembl.1
Natural variantiVAR_00443864N → S in HNPCC2. Corresponds to variant dbSNP:rs637509521 PublicationEnsembl.1
Natural variantiVAR_00443967G → R in HNPCC2; no effect on MLH1 splicing; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. Corresponds to variant dbSNP:rs6375020611 PublicationsEnsembl.1
Natural variantiVAR_01290367G → W in HNPCC2. Corresponds to variant dbSNP:rs637502062 PublicationsEnsembl.1
Natural variantiVAR_00444068I → N in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637502811 PublicationEnsembl.1
Natural variantiVAR_00444169R → K in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637516611 PublicationEnsembl.1
Natural variantiVAR_04339371Missing in HNPCC2; decreased mismatch repair activity; loss of protein expression. 2 Publications1
Natural variantiVAR_00444277C → R in HNPCC2; decreased mismatch repair activity; loss of nuclear localization; normal interaction with PMS2. Corresponds to variant dbSNP:rs637498595 PublicationsEnsembl.1
Natural variantiVAR_01290580F → V in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637499903 PublicationsEnsembl.1
Natural variantiVAR_01290684K → E in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637506413 PublicationsEnsembl.1
Natural variantiVAR_05452398G → S Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676077251 PublicationEnsembl.1
Natural variantiVAR_022664101G → D in HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676077272 PublicationsEnsembl.1
Natural variantiVAR_054524101G → S Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676077261 PublicationEnsembl.1
Natural variantiVAR_043394102E → K in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637504531 PublicationEnsembl.1
Natural variantiVAR_004444107I → R in HNPCC2; decreased mismatch repair activity; normal interaction with PMS2; loss of protein expression; loss of nuclear localization. Corresponds to variant dbSNP:rs637505073 PublicationsEnsembl.1
Natural variantiVAR_076341109H → P in HNPCC2; decreased mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs5877790042 PublicationsEnsembl.1
Natural variantiVAR_076342111A → P in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs5877790052 PublicationsEnsembl.1
Natural variantiVAR_012907111A → V in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637505392 PublicationsEnsembl.1
Natural variantiVAR_054525116T → K Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs637504651 PublicationEnsembl.1
Natural variantiVAR_004445117T → M in HNPCC2; decreased mismatch repair activity; no effect on MLH1 splicing; fails to interact with PMS2 and EXO1; loss of nuclear localization. Corresponds to variant dbSNP:rs6375078111 PublicationsEnsembl.1
Natural variantiVAR_004446117T → R in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637507811 PublicationEnsembl.1
Natural variantiVAR_054526126Y → N Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2000768931 PublicationEnsembl.1
Natural variantiVAR_012908128A → P in HNPCC2. Corresponds to variant dbSNP:rs637508661 PublicationEnsembl.1
Natural variantiVAR_043397155L → R in HNPCC2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. Corresponds to variant dbSNP:rs637508912 PublicationsEnsembl.1
Natural variantiVAR_012909182R → G in HNPCC2; incomplete. Corresponds to variant dbSNP:rs637502112 PublicationsEnsembl.1
Natural variantiVAR_022666182R → K in HNPCC2. Corresponds to variant dbSNP:rs5877790211 PublicationEnsembl.1
Natural variantiVAR_004447185V → G in HNPCC2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs637505153 PublicationsEnsembl.1
Natural variantiVAR_043398185V → L in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637500121 PublicationEnsembl.1
Natural variantiVAR_004448193S → P in HNPCC2. Corresponds to variant dbSNP:rs637510211 PublicationEnsembl.1
Natural variantiVAR_054527215N → S Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676077751 PublicationEnsembl.1
Natural variantiVAR_054528216I → S Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676077761 PublicationEnsembl.1
Natural variantiVAR_004449217R → C in HNPCC2; unknown pathological significance; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs49869844 PublicationsEnsembl.1
Natural variantiVAR_004452226 – 295Missing in HNPCC2. Add BLAST70
Natural variantiVAR_004451226R → L in HNPCC2. Corresponds to variant dbSNP:rs637517111 PublicationEnsembl.1
Natural variantiVAR_076343233Missing in HNPCC2; loss of nuclear localization. 1 Publication1
Natural variantiVAR_043399234E → G in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637506961 PublicationEnsembl.1
Natural variantiVAR_012911244G → D in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637503033 PublicationsEnsembl.1
Natural variantiVAR_043400247S → P in HNPCC2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. Corresponds to variant dbSNP:rs637509483 PublicationsEnsembl.1
Natural variantiVAR_054529260L → F in HNPCC2; unknown pathological significance; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs637506421 PublicationEnsembl.1
Natural variantiVAR_012913262Missing in HNPCC2. 1 Publication1
Natural variantiVAR_043402264H → Y in HNPCC2. Corresponds to variant dbSNP:rs637515971 PublicationEnsembl.1
Natural variantiVAR_054530265R → C in HNPCC2; results in partial MLH1 exon 10 skipping on ex vivo splicing assay; decreased mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs637511943 PublicationsEnsembl.1
Natural variantiVAR_012914265R → H Rare polymorphism; associated with HNPCC2; results in partial MLH1 exon 10 skipping on ex vivo splicing assay; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637514484 PublicationsEnsembl.1
Natural variantiVAR_076344265R → S in HNPCC2; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637511941 PublicationEnsembl.1
Natural variantiVAR_043403282A → G in HNPCC2. Corresponds to variant dbSNP:rs637503601 PublicationEnsembl.1
Natural variantiVAR_043404292L → P in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637505172 PublicationsEnsembl.1
Natural variantiVAR_012916295S → T in HNPCC2. Corresponds to variant dbSNP:rs637501441 PublicationEnsembl.1
Natural variantiVAR_043405304D → V in HNPCC2. Corresponds to variant dbSNP:rs637509931 PublicationEnsembl.1
Natural variantiVAR_054531320E → D Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078111 PublicationEnsembl.1
Natural variantiVAR_043406321S → I in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637502861 PublicationEnsembl.1
Natural variantiVAR_004453326V → A in HNPCC2; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs637510493 PublicationsEnsembl.1
Natural variantiVAR_012918329H → P in HNPCC2; loss of protein expression; loss of nuclear localization. Corresponds to variant dbSNP:rs637507105 PublicationsEnsembl.1
Natural variantiVAR_043408330Missing in HNPCC2; results in weak MLH1 exon 11 skipping on ex vivo splicing assay; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. 3 Publications1
Natural variantiVAR_043409338N → S in HNPCC2. Corresponds to variant dbSNP:rs637514671 PublicationEnsembl.1
Natural variantiVAR_022667379Y → C in HNPCC2. Corresponds to variant dbSNP:rs1430095281 PublicationEnsembl.1
Natural variantiVAR_043410385R → C in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637507601 PublicationEnsembl.1
Natural variantiVAR_043411385R → P in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637504301 PublicationEnsembl.1
Natural variantiVAR_076345389R → W in HNPCC2; unknown pathological significance; no effect on nuclear localization; normal interaction with PMS2 and EXO1. Corresponds to variant dbSNP:rs617516441 PublicationEnsembl.1
Natural variantiVAR_012920441A → T in HNPCC2. Corresponds to variant dbSNP:rs637503652 PublicationsEnsembl.1
Natural variantiVAR_043412443K → Q in HNPCC2; unknown pathological significance; no decrease in mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs342137264 PublicationsEnsembl.1
Natural variantiVAR_076347460E → A in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs2020384991 PublicationEnsembl.1
Natural variantiVAR_043414474R → Q in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637510832 PublicationsEnsembl.1
Natural variantiVAR_054532474R → W Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs1479398381 PublicationEnsembl.1
Natural variantiVAR_043415485D → E in HNPCC2. Corresponds to variant dbSNP:rs637509561 PublicationEnsembl.1
Natural variantiVAR_043416485D → H in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637503141 PublicationEnsembl.1
Natural variantiVAR_004455492A → T in HNPCC2; also found in sporadic colorectal cancer. Corresponds to variant dbSNP:rs637511451 PublicationEnsembl.1
Natural variantiVAR_004456506V → A in HNPCC2. Corresponds to variant dbSNP:rs63749909Ensembl.1
Natural variantiVAR_054533539A → D Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078431 PublicationEnsembl.1
Natural variantiVAR_004457542Q → L in HNPCC2; type II; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637505113 PublicationsEnsembl.1
Natural variantiVAR_043417542Q → P in HNPCC2. Corresponds to variant dbSNP:rs637505111 PublicationEnsembl.1
Natural variantiVAR_012921549L → P in HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs637502893 PublicationsEnsembl.1
Natural variantiVAR_043418550L → P in HNPCC2; decreased mismatch repair activity; defective in interaction with PMS2 and EXO1; loss of protein expression; may lose nuclear localization. Corresponds to variant dbSNP:rs637501934 PublicationsEnsembl.1
Natural variantiVAR_012922551N → T in HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs637502713 PublicationsEnsembl.1
Natural variantiVAR_022668559L → R in HNPCC2. Corresponds to variant dbSNP:rs637500591 PublicationEnsembl.1
Natural variantiVAR_012923565I → F in HNPCC2. Corresponds to variant dbSNP:rs637500621 PublicationEnsembl.1
Natural variantiVAR_004458574L → P in HNPCC2; type I; abrogates interaction with EXO1. Corresponds to variant dbSNP:rs637516084 PublicationsEnsembl.1
Natural variantiVAR_076348578 – 632Missing in HNPCC2; decreased mismatch repair activity; defective in interaction with PMS2. 1 PublicationAdd BLAST55
Natural variantiVAR_004459578E → G in HNPCC2 and CRC; unknown pathological significance; no decrease in mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs637516123 PublicationsEnsembl.1
Natural variantiVAR_076349582L → F in HNPCC2; decreased mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs637517132 PublicationsEnsembl.1
Natural variantiVAR_004460582L → V in HNPCC2; type II. Corresponds to variant dbSNP:rs637517131 PublicationEnsembl.1
Natural variantiVAR_054534585L → R Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078651 PublicationEnsembl.1
Natural variantiVAR_015689586A → P in HNPCC2. Corresponds to variant dbSNP:rs637511761 PublicationEnsembl.1
Natural variantiVAR_012924588L → P in HNPCC2. Corresponds to variant dbSNP:rs637505751 PublicationEnsembl.1
Natural variantiVAR_043419589A → D in HNPCC2; decreased mismatch repair activity; loss of interaction with PMS2 and EXO1; loss of protein expression; may lose nuclear localization. Corresponds to variant dbSNP:rs637500164 PublicationsEnsembl.1
Natural variantiVAR_043420596Missing in HNPCC2. 1
Natural variantiVAR_012925603P → R in HNPCC2; unknown pathological significance; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs358319313 PublicationsEnsembl.1
Natural variantiVAR_012926607L → H in HNPCC2; unknown pathological significance; also found in lobular carcinoma in situ of the breast; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs412952845 PublicationsEnsembl.1
Natural variantiVAR_043422612Missing in HNPCC2; loss of protein expression; loss of nuclear localization. 2 Publications1
Natural variantiVAR_004461616Missing in HNPCC2 and MMRCS; abrogates interaction with EXO1; loss of protein expression; loss of nuclear localization; no effect on MLH1 splicing. 11 Publications1
Natural variantiVAR_004462618K → A in HNPCC2; unknown pathological significance; requires 2 nucleotide substitutions; interacts weakly with PMS2; no decrease in mismatch repair activity; no effect on nuclear localization. Corresponds to variant dbSNP:rs3550253112 PublicationsEnsembl.1
Natural variantiVAR_004463618K → T in HNPCC2; type II; loss of nuclear localization. Corresponds to variant dbSNP:rs637504497 PublicationsEnsembl.1
Natural variantiVAR_043423618Missing in HNPCC2. 1 Publication1
Natural variantiVAR_054535619A → P Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078661 PublicationEnsembl.1
Natural variantiVAR_012927622L → H in HNPCC2. Corresponds to variant dbSNP:rs637506931 PublicationEnsembl.1
Natural variantiVAR_043425623A → P in HNPCC2; unknown pathological significance. 1 Publication1
Natural variantiVAR_004464626 – 627FS → ST in HNPCC2. 2
Natural variantiVAR_043426631D → A in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637502401 PublicationEnsembl.1
Natural variantiVAR_076350633 – 663Missing in HNPCC2; decreased mismatch repair activity; defective in interaction with PMS2; loss of protein expression; loss of nuclear localization. 1 PublicationAdd BLAST31
Natural variantiVAR_043428636L → P in HNPCC2. Corresponds to variant dbSNP:rs637508251 PublicationEnsembl.1
Natural variantiVAR_054536640P → L Associated with HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078751 PublicationEnsembl.1
Natural variantiVAR_043429640P → S in HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs637497922 PublicationsEnsembl.1
Natural variantiVAR_043430646Y → C in HNPCC2; defective in interaction with PMS2 and EXO1; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs350450675 PublicationsEnsembl.1
Natural variantiVAR_012928648P → L in HNPCC2; unknown pathological significance; defective in interaction with PMS2 and EXO1; may lose nuclear localization; loss of protein expression; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs637506105 PublicationsEnsembl.1
Natural variantiVAR_022669648P → S in HNPCC2; the protein is unstable; loss of nuclear localization; loss of protein expression; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs637508994 PublicationsEnsembl.1
Natural variantiVAR_043431654P → L in HNPCC2; decreased mismatch repair activity; defective in interaction with PMS2 and EXO1; loss of protein expression; may lose nuclear localization. Corresponds to variant dbSNP:rs637507264 PublicationsEnsembl.1
Natural variantiVAR_043432655I → V in HNPCC2; also found in an endometrial cancer sample; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs559074332 PublicationsEnsembl.1
Natural variantiVAR_054537656F → S in HNPCC2; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078761 PublicationEnsembl.1
Natural variantiVAR_043433657Missing in HNPCC2; unknown pathological significance. 1 Publication1
Natural variantiVAR_012929659R → L in HNPCC2. Corresponds to variant dbSNP:rs637499002 PublicationsEnsembl.1
Natural variantiVAR_004465659R → P in HNPCC2; interacts only very weakly with PMS2; abrogates interaction with EXO1; decreased mismatch repair activity; may lose nuclear localization. Corresponds to variant dbSNP:rs637499006 PublicationsEnsembl.1
Natural variantiVAR_043434659R → Q in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637499002 PublicationsEnsembl.1
Natural variantiVAR_012930662T → P in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs5877789642 PublicationsEnsembl.1
Natural variantiVAR_054538666W → R in HNPCC2; unknown pathological significance; no effect on MLH1 splicing. Corresponds to variant dbSNP:rs2676078871 PublicationEnsembl.1
Natural variantiVAR_004466681A → T in HNPCC2 and CRC; abrogates interaction with EXO1; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs637502177 PublicationsEnsembl.1
Natural variantiVAR_012931687R → W in HNPCC2; unknown pathological significance. Corresponds to variant dbSNP:rs637512754 Publications