PPP4C: Protein Phosphatase 4 Catalytic Subunit
A key serine/threonine phosphatase regulating cell cycle, DNA repair, and apoptosis
Gene Information Card
| Symbol | PPP4C |
|---|---|
| Full Name | Protein Phosphatase 4 Catalytic Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 5531 ncbi.nlm.nih.gov/gene/5531 |
| Ensembl ID | ENSG00000140987 |
| UniProt ID | P60510 |
| OMIM ID | 602035 |
| HGNC ID | 9321 |
| Aliases | PP4C, PPX, PPP4 |
Description
PPP4C encodes the catalytic subunit of protein phosphatase 4 (PP4), a serine/threonine phosphatase involved in diverse cellular processes including cell cycle progression, DNA damage checkpoint recovery, homologous recombination repair, apoptosis, and microtubule organization. PP4C forms complexes with regulatory subunits to achieve substrate specificity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Dysregulation of PP4C expression may alter DNA repair and cell cycle control | PMID: 23431136 |
| Lung cancer | PPP4C overexpression linked to poor prognosis and increased proliferation | PMID: 25944712 |
| Hepatocellular carcinoma | PPP4C promotes tumor growth via dephosphorylation of HDAC2 | PMID: 28793258 |
| Colorectal cancer | PPP4C upregulation associated with metastasis and chemoresistance | PMID: 29395074 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | High |
| Lymph node | 15.2 | High |
| Brain | 12.8 | Medium |
| Liver | 10.1 | Medium |
| Heart | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | Embryonic kidney cells |
| HeLa | 19.7 | Cervical cancer cells |
| A549 | 17.3 | Lung cancer cells |
| MCF7 | 15.6 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | Rare | p.Met1Val; potential loss of start codon |
| c.287C>T | Missense | 0.01% | p.Thr96Ile; unknown functional effect |
| c.512G>A | Missense | 0.005% | p.Arg171Gln; observed in cancer samples |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in PPP4C; likely essential for cell viability.
Gain of Function (GOF)
Overexpression in multiple cancers suggests potential gain-of-function role in tumorigenesis.
Dominant Negative (DN)
No dominant-negative mutations described in PPP4C.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA damage response (ATM/ATR signaling)
• Homologous recombination repair
• Cell cycle checkpoint control
• Apoptosis signaling
Protein Summary
PPP4C is a 307-amino acid protein (35 kDa) that functions as the catalytic core of protein phosphatase 4. It dephosphorylates key substrates such as HDAC2, RPA2, and KAP1, thereby regulating chromatin remodeling, DNA repair, and cell cycle progression. PP4C activity is essential for embryonic development and its dysregulation contributes to cancer.
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