PPP4C
protein-codingprotein phosphatase 4 catalytic subunit, the group of Protein phosphatase catalytic subunits
Gene summary
Enables protein serine/threonine phosphatase activity. Involved in regulation of double-strand break repair via homologous recombination. Located in chromatin; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPP4C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002720.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 8 | 8 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 13 | 0 | 0 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002711.1 | 8 | MANE Select | |
| Ensembl | ENSP00000279387.7 | 8 | MANE Select | |
| RefSeq | NP_001290432.1 | 8 | Standard | |
| RefSeq | NP_001290433.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ppp4cb | Danio rerio | Structure: trunk Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glucagon signaling pathway - Homo sapiens (human)
- IGF-Ncore
- HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
- DNA Repair
- DNA Double-Strand Break Repair
Biological Process
- protein dephosphorylation
- regulation of double-strand break repair via homologous recombination
- NIK/NF-kappaB signaling
Molecular Function
- NF-kappaB-inducing kinase activity
- protein serine/threonine phosphatase activity
- protein binding
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- microtubule organizing center
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000279387
- Coding exons
- 8
- Length
- 9400
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.55 | 60 | 202 | 0.297 | 0.0000125 | 2019 |
| Missense (PolyPhen) | 13 | 84.78 | 0.15334 | 822 | ||
| Synonymous | -0.968 | 96 | 84.7 | 1.13 | 0.00000599 | 588 |
| Loss of Function | 3.15 | 4 | 18.7 | 0.214 | 9.70e-7 | 187 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. The PPP4C- PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on Ser-140 (gamma-H2AFX) generated during DNA replication and required for DNA double strand break repair. Dephosphorylates NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1 activity in interphase (By similarity). In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin. {ECO:0000250, ECO:0000269|PubMed:11698396, ECO:0000269|PubMed:12668731, ECO:0000269|PubMed:12934076, ECO:0000269|PubMed:1336397, ECO:0000269|PubMed:15805470, ECO:0000269|PubMed:18347064, ECO:0000269|PubMed:18487071, ECO:0000269|PubMed:18614045, ECO:0000269|PubMed:18758438, ECO:0000269|PubMed:20154705}.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.127
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |