PGAM5
PGAM5: A Mitochondrial Phosphoglycerate Mutase Family Member Involved in Mitophagy and Apoptosis
Gene Information Card
| Symbol | PGAM5 |
|---|---|
| Full Name | PGAM family member 5, serine/threonine protein phosphatase, mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.33 |
| NCBI Gene ID | 192111 ncbi.nlm.nih.gov/gene/192111 |
| Ensembl ID | ENSG00000178919 |
| UniProt ID | Q96HS1 |
| OMIM ID | 614711 |
| HGNC ID | 28763 |
| Aliases | PGAM5, B5, PGAM5A, PGAM5B, MGC2615 |
Description
PGAM5 (PGAM family member 5) is a mitochondrial serine/threonine protein phosphatase that belongs to the phosphoglycerate mutase family. It plays a critical role in mitochondrial homeostasis, mitophagy, and apoptosis by dephosphorylating key substrates such as KEAP1, NRF2, and FUNDC1. PGAM5 is involved in the PINK1/Parkin pathway and regulates mitochondrial dynamics and cell death.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Parkinson's disease) | PGAM5 regulates mitophagy via PINK1/Parkin; loss of function impairs mitochondrial clearance | PMID: 24652937 |
| Cancer (e.g., hepatocellular carcinoma) | PGAM5 modulates apoptosis and NRF2 signaling; altered expression linked to tumor progression | PMID: 25944712 |
| Inflammatory diseases | PGAM5 dephosphorylates KEAP1, activating NRF2 and anti-inflammatory responses | PMID: 24652937 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 10.2 | Medium |
| Liver | 8.9 | Medium |
| Brain | 6.3 | Low |
| Kidney | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | High expression |
| HEK293 | 12.8 | Medium expression |
| SH-SY5Y | 9.4 | Medium expression |
| HepG2 | 11.1 | Medium expression |
| K562 | 6.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; likely loss of function |
| c.317C>T (p.Pro106Leu) | Missense | <0.01% | Unknown significance; reported in ClinVar |
| c.464_465del (p.Glu155Glyfs*2) | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations lead to truncated or absent protein, impairing mitophagy and increasing oxidative stress.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitophagy - PINK1/Parkin pathway
• NRF2-ARE signaling pathway
• Apoptosis - mitochondrial pathway
• FUNDC1-mediated mitophagy
Protein Summary
PGAM5 is a 289-amino acid mitochondrial phosphatase with a conserved phosphoglycerate mutase domain. It localizes to the outer mitochondrial membrane and functions as a serine/threonine phosphatase. PGAM5 dephosphorylates KEAP1, leading to NRF2 stabilization and antioxidant response, and dephosphorylates FUNDC1 to promote mitophagy. It also interacts with PINK1 and Parkin to regulate mitochondrial quality control. PGAM5 is implicated in neurodegeneration, cancer, and inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PGAM5 Knockout HEK293 Cell Line | EDJ-KQ883 | Human | 192111 | Details Get a Quote |
| PGAM5 Knockout A-549 Cell Line | EDJ-KQ21046 | Human | 192111 | Details Get a Quote |
| PGAM5 Knockout HCT 116 Cell Line | EDJ-KQ21047 | Human | 192111 | Details Get a Quote |
| PGAM5 Knockout HeLa Cell Line | EDJ-KQ21048 | Human | 192111 | Details Get a Quote |
| PGAM5 Knockout PK-15 Cell Line | EDJ-KZ391 | Pig | 106508765 | Details Get a Quote |
