MLH3 Gene - Mismatch Repair Protein
Key player in DNA mismatch repair and microsatellite stability
Gene Information Card
| Symbol | MLH3 |
|---|---|
| Full Name | mutL homolog 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 27030 ncbi.nlm.nih.gov/gene/27030 |
| Ensembl ID | ENSG00000119682 |
| UniProt ID | Q9UHC1 |
| OMIM ID | 604395 |
| HGNC ID | 7128 |
| Aliases | MUTL homolog 3, DNA mismatch repair protein Mlh3 |
Description
The MLH3 gene encodes a protein that is part of the DNA mismatch repair (MMR) system. It forms a heterodimer with MLH1 (MutLα) and is involved in repairing base-base mismatches and insertion-deletion loops that occur during DNA replication. MLH3 is also implicated in meiotic recombination and microsatellite stability. Mutations in MLH3 are associated with hereditary non-polyposis colorectal cancer (Lynch syndrome) and other cancers with microsatellite instability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (hereditary non-polyposis colorectal cancer) | Loss-of-function mutations in MLH3 impair mismatch repair, leading to microsatellite instability and increased cancer risk. | ClinVar, OMIM |
| Colorectal cancer | MLH3 mutations contribute to microsatellite instability in sporadic and hereditary colorectal cancers. | COSMIC, NCBI |
| Endometrial cancer | Defective MMR due to MLH3 alterations is linked to microsatellite instability in endometrial tumors. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Colon | 8.2 | Low |
| Small intestine | 7.9 | Low |
| Ovary | 6.1 | Low |
| Brain | 3.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.1 | Cervical cancer cell line |
| HCT116 | 9.5 | Colorectal carcinoma cell line |
| MCF7 | 7.8 | Breast cancer cell line |
| A549 | 6.3 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2531C>T (p.Pro844Leu) | Missense | Rare | Likely pathogenic; associated with Lynch syndrome |
| c.2931_2932del (p.Glu978Argfs*2) | Frameshift | Rare | Loss of function; microsatellite instability |
| c.2000A>G (p.Asn667Ser) | Missense | Unknown | Uncertain significance; reported in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the ATPase domain impair mismatch repair activity.
Gain of Function (GOF)
Not well characterized; no clear gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may interfere with heterodimer formation with MLH1, exerting a dominant-negative effect.
View complete mutation data：
Gene Ontology (GO)
| • DNA mismatch repair | • ATP binding |
| • protein heterodimerization activity | • meiotic recombination |
| • nucleotide binding |
Pathways
• Mismatch repair (MMR) pathway
• Meiotic recombination pathway
Protein Summary
The MLH3 protein (770 amino acids) contains an N-terminal ATPase domain and a C-terminal domain involved in protein-protein interactions. It forms a heterodimer with MLH1 to create MutLγ, which is essential for repairing DNA mismatches and insertion-deletion loops. MLH3 also plays a role in meiotic crossover formation. Defects in MLH3 lead to microsatellite instability and increased susceptibility to Lynch syndrome-associated cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MLH3 Knockout HEK293 Cell Line | EDJ-KQ51199 | Human | 27030 | Details Get a Quote |
| MLH3 Knockout HeLa Cell Line | EDJ-KQ55987 | Human | 27030 | Details Get a Quote |
| MLH3 Knockout A-549 Cell Line | EDJ-KQ64471 | Human | 27030 | Details Get a Quote |
| MLH3 Knockout HCT 116 Cell Line | EDJ-KQ72929 | Human | 27030 | Details Get a Quote |
