PPP3CC
protein-codingprotein phosphatase 3 catalytic subunit gamma, the group of Protein phosphatase catalytic subunits
Gene summary
Calcineurin is a calcium-dependent, calmodulin-stimulated protein phosphatase involved in the downstream regulation of dopaminergic signal transduction. Calcineurin is composed of a regulatory subunit and a catalytic subunit. The protein encoded by this gene represents one of the regulatory subunits that has been found for calcineurin. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~100.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPP3CC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005605.5. 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 | 1 | 1 | ||||
| missense | 69 | 2 | 71 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 73 | 2 | 0 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005596.2 | 14 | MANE Select | |
| Ensembl | ENSP00000240139.5 | 14 | MANE Select | |
| RefSeq | NP_001230903.1 | 15 | Standard | |
| RefSeq | NP_001230904.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Oxytocin signaling pathway - Homo sapiens (human)
- T cell receptor signaling pathway - Homo sapiens (human)
- B cell receptor signaling pathway - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- VEGF signaling pathway - Homo sapiens (human)
Biological Process
- protein dephosphorylation
- brain development
- calcineurin-NFAT signaling cascade
- calcineurin-mediated signaling
- positive regulation of synaptic vesicle endocytosis
Molecular Function
- protein binding
- calmodulin binding
- calmodulin-dependent protein phosphatase activity
- metal ion binding
Cellular Component
- cytoplasm
- cytosol
- calcineurin complex
- glutamatergic synapse
- presynaptic cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397775
- Coding exons
- 15
- Length
- 100321
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125747
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 222 | 284 | 0.780 | 0.0000148 | 3404 |
| Missense (PolyPhen) | 76 | 108.41 | 0.70107 | 1305 | ||
| Synonymous | 1.31 | 86 | 103 | 0.836 | 0.00000549 | 971 |
| Loss of Function | 3.86 | 7 | 29.7 | 0.236 | 0.00000157 | 359 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.000039 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32. {ECO:0000269|PubMed:19154138}.;
Recessive Scores
- pRec
- 0.161
Intolerance Scores
- LoFtool
- 0.612
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.900
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |