PMS2 Gene - DNA Mismatch Repair Protein
PMS2: Key player in DNA mismatch repair and Lynch syndrome
Gene Information Card
| Symbol | PMS2 |
|---|---|
| Full Name | PMS1 homolog 2, mismatch repair system component |
| Gene Type | protein-coding |
| Chromosomal Location | 7p22.1 |
| NCBI Gene ID | 5395 ncbi.nlm.nih.gov/gene/5395 |
| Ensembl ID | ENSG00000122512 |
| UniProt ID | P54278 |
| OMIM ID | 600259 |
| HGNC ID | 9122 |
| Aliases | PMS2CL, hPMS2, MLH4, PMS2L1 |
Description
The PMS2 gene encodes a protein that is a critical component of the DNA mismatch repair (MMR) system. It forms a heterodimer with MLH1 (MutLα complex) to correct DNA replication errors, such as base-base mismatches and insertion-deletion loops. Loss of PMS2 function leads to microsatellite instability and increased mutation rates, predisposing individuals to hereditary nonpolyposis colorectal cancer (Lynch syndrome) and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (hereditary nonpolyposis colorectal cancer) | Germline loss-of-function mutations in PMS2 impair DNA mismatch repair, leading to microsatellite instability and increased risk of colorectal, endometrial, and other cancers. | ClinVar, OMIM |
| Turcot syndrome | Biallelic PMS2 mutations cause constitutional mismatch repair deficiency (CMMR-D), associated with brain tumors and colorectal polyps. | OMIM |
| Mismatch repair cancer syndrome | Biallelic PMS2 mutations result in early-onset cancers, including hematologic malignancies and brain tumors. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 12.5 | Medium |
| Endometrium | 8.3 | Low |
| Ovary | 6.7 | Low |
| Testis | 15.2 | Medium |
| Brain | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.4 | Cervical cancer cell line |
| HCT116 | 2.1 | Colorectal cancer cell line (PMS2 deficient) |
| MCF7 | 14.8 | Breast cancer cell line |
| A549 | 11.3 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.137G>T (p.Ser46Ile) | Missense | Rare | Likely pathogenic; disrupts ATPase activity |
| c.943C>T (p.Gln315Ter) | Nonsense | 1-2% in Lynch syndrome | Loss of function; truncating |
| c.2007-1G>A | Splice site | Rare | Loss of function; exon skipping |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein |
Mutation functional classification
Loss of Function (LOF)
Most PMS2 mutations are loss-of-function, leading to deficient mismatch repair and microsatellite instability.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting heterodimer formation with MLH1.
View complete mutation data：
Gene Ontology (GO)
| • DNA mismatch repair | • ATP binding |
| • protein heterodimerization activity | • nucleus |
| • damaged DNA binding |
Pathways
• Mismatch repair (KEGG: hsa03430)
• Colorectal cancer (KEGG: hsa05210)
Protein Summary
PMS2 is a 862-amino acid protein that functions as the endonuclease subunit of the MutLα complex. It contains an N-terminal ATPase domain and a C-terminal endonuclease domain. The protein interacts with MLH1 to form a heterodimer that nicks the daughter strand near mismatches, facilitating excision and resynthesis. PMS2 is ubiquitously expressed but shows higher levels in testis and colon.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PMS2 Knockout HEK293 Cell Line | EDC07583 | Human | 5395 | Details Get a Quote |
| RBPMS2 Knockout HEK293 Cell Line | EDJ-KQ15017 | Human | 348093 | Details Get a Quote |
| RBPMS2 Knockout A-549 Cell Line | EDJ-KQ44287 | Human | 348093 | Details Get a Quote |
| PMS2 Knockout A-549 Cell Line | EDJ-KQ23427 | Human | 5395 | Details Get a Quote |
| PMS2 Knockout HCT 116 Cell Line | EDJ-KQ23428 | Human | 5395 | Details Get a Quote |
| PMS2 Knockout HeLa Cell Line | EDJ-KQ23429 | Human | 5395 | Details Get a Quote |
| RBPMS2 Knockout HCT 116 Cell Line | EDJ-KQ45547 | Human | 348093 | Details Get a Quote |
| RBPMS2 Knockout HeLa Cell Line | EDJ-KQ45548 | Human | 348093 | Details Get a Quote |
| PMS2 (p.P470S) Point Mutation in HAP1 Cell Line | EDC03581 | Human | 5395 | Details Get a Quote |
| PMS2 (c.2007-4G>A )Point Mutation in HAP1 Cell Line | EDC03580 | Human | 5395 | Details Get a Quote |
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