PPM1K
Protein Phosphatase, Mg2+/Mn2+ Dependent 1K
Gene Information Card
| Symbol | PPM1K |
|---|---|
| Full Name | Protein Phosphatase, Mg2+/Mn2+ Dependent 1K |
| Gene Type | Protein coding |
| Chromosomal Location | 4q22.1 |
| NCBI Gene ID | 152926 ncbi.nlm.nih.gov/gene/152926 |
| Ensembl ID | ENSG00000163644 |
| UniProt ID | Q8N3J5 |
| OMIM ID | 611065 |
| HGNC ID | 25038 |
| Aliases | PP2Cm, PP2C kappa, mitochondrial phosphatase |
Description
PPM1K encodes a mitochondrial serine/threonine phosphatase that specifically dephosphorylates and activates the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, a key enzyme in the catabolism of branched-chain amino acids (leucine, isoleucine, valine). Loss-of-function mutations impair BCKDH activity and are associated with maple syrup urine disease (MSUD) type 2.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maple syrup urine disease type 2 | Loss-of-function mutations in PPM1K reduce BCKDH phosphatase activity, leading to accumulation of branched-chain amino acids and their keto acids. | ClinVar, OMIM |
| Branched-chain ketoaciduria | Impaired dephosphorylation of BCKDH E1-alpha subunit due to PPM1K deficiency. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Low |
| Skeletal muscle | 4.7 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Hepatocyte model |
| HEK293 | 5.4 | Embryonic kidney |
| K562 | 2.8 | Leukemia line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, no protein |
| c.331C>T (p.Arg111*) | Nonsense | Rare | Premature truncation, loss of function |
| c.502G>A (p.Gly168Arg) | Missense | Rare | Impaired catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most reported PPM1K mutations are loss-of-function, reducing BCKDH phosphatase activity and causing MSUD.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine phosphatase activity | • magnesium ion binding |
| • manganese ion binding | • dephosphorylation |
| • mitochondrion | • branched-chain amino acid catabolic process |
Pathways
• Branched-chain amino acid degradation (Reactome: R-HSA-70895)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
Protein Summary
PPM1K (PP2Cm) is a 382-amino acid mitochondrial phosphatase that specifically dephosphorylates the E1-alpha subunit of the BCKDH complex, activating it. It requires Mg2+ or Mn2+ for activity. Deficiency leads to impaired branched-chain amino acid catabolism and MSUD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPM1K Knockout HEK293 Cell Line | EDJ-KQ11491 | Human | 152926 | Details Get a Quote |
| PPM1K Knockout A-549 Cell Line | EDJ-KQ39812 | Human | 152926 | Details Get a Quote |
| PPM1K Knockout HCT 116 Cell Line | EDJ-KQ39813 | Human | 152926 | Details Get a Quote |
| PPM1K Knockout HeLa Cell Line | EDJ-KQ39814 | Human | 152926 | Details Get a Quote |
| PPM1K Knockout HAP1 Cell Line | EDC09471 | Human | 152926 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
