PPP1CA
protein phosphatase 1 catalytic subunit alpha, the group of Protein phosphatase catalytic subunits
Basic information
Region (hg38): 11:67398181-67421183
Previous symbols: [ "PPP1A" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (22 variants)
- not_provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1CA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002708.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 20 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 23 | 1 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PPP1CA | protein_coding | protein_coding | ENST00000312989 | 7 | 23001 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.986 | 0.0141 | 125704 | 0 | 12 | 125716 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.26 | 75 | 207 | 0.362 | 0.0000123 | 2227 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000905 | 0.0000905 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000188 | 0.000185 |
| European (Non-Finnish) | 0.0000442 | 0.0000440 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
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}.;
- Pathway
- 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);Dopaminergic synapse - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);mRNA surveillance pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Herpes simplex infection - Homo sapiens (human);Excitatory Neural Signalling Through 5-HTR 4 and Serotonin;Excitatory Neural Signalling Through 5-HTR 7 and Serotonin ;Excitatory Neural Signalling Through 5-HTR 6 and Serotonin ;Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin;Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone;Intracellular Signalling Through Histamine H2 Receptor and Histamine;TGF-Ncore;Sphingolipid Metabolism;Nicotine Activity on Dopaminergic Neurons;Common Pathways Underlying Drug Addiction;Focal Adhesion;Signaling by GPCR;Signal Transduction;Circadian Clock;regulation of ck1/cdk5 by type 1 glutamate receptors;protein kinase a at the centrosome;Metabolism of lipids;Metabolism;AndrogenReceptor;DARPP-32 events;BMP receptor signaling;Triglyceride catabolism;Triglyceride metabolism;Opioid Signalling;G alpha (i) signalling events;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;GPCR downstream signalling;TGF-beta receptor signaling activates SMADs;ALK1 signaling events;TGF-beta receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.459
Intolerance Scores
- loftool
- 0.451
- rvis_EVS
- -0.36
- rvis_percentile_EVS
- 28.63
Haploinsufficiency Scores
- pHI
- 0.996
- hipred
- Y
- hipred_score
- 0.711
- ghis
- 0.651
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ppp1ca
- Phenotype
Zebrafish Information Network
- Gene name
- ppp1caa
- Affected structure
- convergent extension
- Phenotype tag
- abnormal
- Phenotype quality
- process quality
Gene ontology
- Biological process
- glycogen metabolic process;regulation of glycogen biosynthetic process;regulation of glycogen catabolic process;protein dephosphorylation;cell cycle;response to lead ion;dephosphorylation;lung development;negative regulation of protein binding;circadian regulation of gene expression;peptidyl-threonine dephosphorylation;regulation of translational initiation by eIF2 alpha dephosphorylation;regulation of circadian rhythm;entrainment of circadian clock by photoperiod;branching morphogenesis of an epithelial tube;cell division;regulation of canonical Wnt signaling pathway;peptidyl-serine dephosphorylation;cell-cell adhesion;beta-catenin destruction complex disassembly;positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
- Cellular component
- protein phosphatase type 1 complex;nuclear chromosome, telomeric region;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;plasma membrane;cell-cell adherens junction;glycogen granule;dendritic spine;perikaryon;extracellular exosome;PTW/PP1 phosphatase complex;presynapse;glutamatergic synapse
- Molecular function
- phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein binding;protein phosphatase 1 binding;phosphatase activity;ribonucleoprotein complex binding;metal ion binding;cadherin binding involved in cell-cell adhesion