PCP4
protein-codingPurkinje cell protein 4
Gene summary
Enables calcium ion binding activity and calmodulin binding activity. Involved in positive regulation of CAMKK-AMPK signaling cascade and positive regulation of neuron differentiation. Located in cytosol and nucleus. Part of protein-containing complex. Biomarker of Huntington's disease and leiomyoma. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.0 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 PCP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006198.3. 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 | 0 | |||||
| missense | 7 | 7 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 9 | 0 | 0 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006189.2 | 3 | MANE Select | |
| Ensembl | ENSP00000329403.5 | 3 | MANE Select | |
| Ensembl | ENSP00000433172.1 | 3 | Standard | |
| Ensembl | ENSP00000699599.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- positive regulation of neuron differentiation
- calmodulin dependent kinase signaling pathway
Molecular Function
- calcium ion binding
- protein binding
- calmodulin binding
Cellular Component
- nucleus
- cytosol
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328619
- Coding exons
- 3
- Length
- 62080
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.613 | 24 | 34.1 | 0.704 | 0.00000180 | 409 |
| Missense (PolyPhen) | 5 | 9.2612 | 0.53989 | 121 | ||
| Synonymous | 0.628 | 8 | 10.6 | 0.755 | 5.41e-7 | 106 |
| Loss of Function | 0.204 | 4 | 4.47 | 0.896 | 2.74e-7 | 42 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a modulator of calcium-binding by calmodulin. Thereby, regulates calmodulin activity and the different processes it controls (PubMed:19106096, PubMed:23204517, PubMed:27876793). For instance, may play a role in neuronal differentiation through activation of calmodulin-dependent kinase signaling pathways (PubMed:21491429). {ECO:0000269|PubMed:19106096, ECO:0000269|PubMed:21491429, ECO:0000269|PubMed:23204517, ECO:0000269|PubMed:27876793}.;
Intolerance Scores
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 59.43
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.283