Human Gene MLH3 (ENST00000355774.7) from GENCODE V38
  Description: Homo sapiens mutL homolog 3 (MLH3), transcript variant 1, mRNA. (from RefSeq NM_001040108)
RefSeq Summary (NM_001040108): 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].
Gencode Transcript: ENST00000355774.7
Gencode Gene: ENSG00000119684.16
Transcript (Including UTRs)
   Position: hg38 chr14:75,013,775-75,051,467 Size: 37,693 Total Exon Count: 13 Strand: -
Coding Region
   Position: hg38 chr14:75,017,082-75,049,655 Size: 32,574 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-09-27 09:51:20

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr14:75,013,775-75,051,467)mRNA (may differ from genome)Protein (1453 aa)
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UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: MLH3_HUMAN
DESCRIPTION: RecName: Full=DNA mismatch repair protein Mlh3; AltName: Full=MutL protein homolog 3;
FUNCTION: Probably involved in the repair of mismatches in DNA.
SUBUNIT: Heterodimer of MLH1 and MLH3. Interacts with MTMR15/FAN1.
SUBCELLULAR LOCATION: Nucleus (Potential).
TISSUE SPECIFICITY: Ubiquitous.
DISEASE: Defects in MLH3 are the cause of hereditary non-polyposis colorectal cancer type 7 (HNPCC7) [MIM:614385]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers 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, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an 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.
DISEASE: Defects in MLH3 are a cause of colorectal cancer (CRC) [MIM:114500].
SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
SEQUENCE CAUTION: Sequence=AAC42005.1; Type=Frameshift; Positions=Several; Sequence=AAC42005.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part;
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mlh3/";

-  MalaCards Disease Associations
  MalaCards Gene Search: MLH3
Diseases sorted by gene-association score: colorectal cancer, hereditary nonpolyposis, type 7* (1200), endometrial cancer* (478), colorectal cancer* (289), colonic benign neoplasm* (163), mlh3-related lynch syndrome* (100), colorectal cancer 7 (21), autosomal dominant disease (7), lynch syndrome (7), early-onset familial alzheimer disease (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.44 RPKM in Thyroid
Total median expression: 176.17 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -47.20151-0.313 Picture PostScript Text
3' UTR -930.803307-0.281 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003594 - ATPase-like_ATP-bd
IPR002099 - DNA_mismatch_repair
IPR013507 - DNA_mismatch_repair_C
IPR014762 - DNA_mismatch_repair_CS
IPR014790 - MutL_C
IPR020568 - Ribosomal_S5_D2-typ_fold
IPR014721 - Ribosomal_S5_D2-typ_fold_subgr

Pfam Domains:
PF01119 - DNA mismatch repair protein, C-terminal domain
PF02518 - Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
PF08676 - MutL C terminal dimerisation domain

ModBase Predicted Comparative 3D Structure on Q9UHC1
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
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Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003682 chromatin binding
GO:0003696 satellite DNA binding
GO:0003697 single-stranded DNA binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016887 ATPase activity
GO:0019237 centromeric DNA binding
GO:0030983 mismatched DNA binding

Biological Process:
GO:0006281 DNA repair
GO:0006298 mismatch repair
GO:0006974 cellular response to DNA damage stimulus
GO:0007130 synaptonemal complex assembly
GO:0007131 reciprocal meiotic recombination
GO:0007140 male meiosis
GO:0007144 female meiosis I
GO:0008104 protein localization

Cellular Component:
GO:0000793 condensed chromosome
GO:0000794 condensed nuclear chromosome
GO:0000795 synaptonemal complex
GO:0001673 male germ cell nucleus
GO:0005634 nucleus
GO:0005712 chiasma
GO:0032300 mismatch repair complex


-  Descriptions from all associated GenBank mRNAs
  BC036866 - Homo sapiens mutL homolog 3 (E. coli), mRNA (cDNA clone IMAGE:5198926), partial cds.
AF195657 - Homo sapiens DNA mismatch repair protein (MLH3) mRNA, complete cds.
JD487579 - Sequence 468603 from Patent EP1572962.
JD155998 - Sequence 137022 from Patent EP1572962.
JD260659 - Sequence 241683 from Patent EP1572962.
JD107904 - Sequence 88928 from Patent EP1572962.
JD157304 - Sequence 138328 from Patent EP1572962.
JD503959 - Sequence 484983 from Patent EP1572962.
JD181690 - Sequence 162714 from Patent EP1572962.
AL833875 - Homo sapiens mRNA; cDNA DKFZp762L056 (from clone DKFZp762L056).
L40399 - Homo sapiens (clone S240ii117/zap112) mRNA, complete cds.
JD122375 - Sequence 103399 from Patent EP1572962.
BC112167 - Homo sapiens mutL homolog 3 (E. coli), mRNA (cDNA clone MGC:138372 IMAGE:8327635), complete cds.
BC143729 - Homo sapiens cDNA clone IMAGE:9052243, containing frame-shift errors.
JD536867 - Sequence 517891 from Patent EP1572962.
JD132969 - Sequence 113993 from Patent EP1572962.
JD502106 - Sequence 483130 from Patent EP1572962.
AB039667 - Homo sapiens mRNA for DNA mismatch repair protein MLH3, complete cds.
HQ258639 - Synthetic construct Homo sapiens clone IMAGE:100073196 mutL homolog 3 (E. coli) (MLH3) gene, encodes complete protein.
KJ898650 - Synthetic construct Homo sapiens clone ccsbBroadEn_08044 MLH3 gene, encodes complete protein.
KR711731 - Synthetic construct Homo sapiens clone CCSBHm_00028935 MLH3 (MLH3) mRNA, encodes complete protein.
KR711732 - Synthetic construct Homo sapiens clone CCSBHm_00028944 MLH3 (MLH3) mRNA, encodes complete protein.
AK298777 - Homo sapiens cDNA FLJ52020 complete cds, highly similar to DNA mismatch repair protein Mlh3.
BC012544 - Homo sapiens mutL homolog 3 (E. coli), mRNA (cDNA clone IMAGE:4081607), with apparent retained intron.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03430 - Mismatch repair

Reactome (by CSHL, EBI, and GO)

Protein Q9UHC1 (Reactome details) participates in the following event(s):

R-HSA-912446 Meiotic recombination
R-HSA-1500620 Meiosis
R-HSA-1474165 Reproduction
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000355774.1, ENST00000355774.2, ENST00000355774.3, ENST00000355774.4, ENST00000355774.5, ENST00000355774.6, MLH3_HUMAN, NM_001040108, P49751, Q56DK9, Q9P292, Q9UHC0, Q9UHC1, uc001xrd.1, uc001xrd.2
UCSC ID: ENST00000355774.7
RefSeq Accession: NM_001040108
Protein: Q9UHC1 (aka MLH3_HUMAN)
CCDS: CCDS9837.1, CCDS32123.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.