PPP1CA
protein-codingprotein phosphatase 1 catalytic subunit alpha, the group of Protein phosphatase catalytic subunits
Gene summary
The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]
- PPP1A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.0 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 PPP1CA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002708.4. 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 | 4 | 1 | 5 | |||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 31 | 1 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002699.1 | 7 | MANE Select | |
| Ensembl | ENSP00000365936.4 | 7 | MANE Select | |
| RefSeq | NP_001008709.1 | 7 | Standard | |
| RefSeq | NP_996756.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ppp1caa | Danio rerio | Structure: convergent extension Quality: process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
- Platelet activation - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
- Oxytocin signaling pathway - Homo sapiens (human)
- Long-term potentiation - Homo sapiens (human)
Biological Process
- glycogen metabolic process
- regulation of glycogen biosynthetic process
- regulation of glycogen catabolic process
- protein dephosphorylation
- cell cycle
Molecular Function
- phosphoprotein phosphatase activity
- protein serine/threonine phosphatase activity
- protein binding
- protein phosphatase 1 binding
- phosphatase activity
Cellular Component
- protein phosphatase type 1 complex
- nuclear chromosome, telomeric region
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000312989
- Coding exons
- 7
- Length
- 23001
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125716
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.26 | 75 | 207 | 0.362 | 0.0000123 | 2227 |
| Missense (PolyPhen) | 16 | 79.64 | 0.2009 | 907 | ||
| Synonymous | -1.20 | 106 | 91.4 | 1.16 | 0.00000632 | 667 |
| Loss of Function | 3.63 | 1 | 17.3 | 0.0578 | 8.72e-7 | 182 |
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 | 0.0 | absent |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5- ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323). {ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323}.;
Recessive Scores
- pRec
- 0.459
Intolerance Scores
- LoFtool
- 0.451
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.63
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |