PRKCA
protein kinase C alpha, the group of MicroRNA protein coding host genes|AGC family kinases|C2 domain containing protein kinases
Basic information
Region (hg38): 17:66302612-66810743
Previous symbols: [ "PKCA" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (17 variants)
- Inborn genetic diseases (8 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKCA gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | |||||
| missense | 11 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | 2 | |||
| non coding ? | 1 | |||||
| Total | 0 | 0 | 9 | 8 | 6 |
Variants in PRKCA
This is a list of pathogenic ClinVar variants found in the PRKCA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-66302841-T-TG | PRKCA-related disorder | Likely benign (Jan 22, 2020) | ||
| 17-66302957-G-A | not specified | Uncertain significance (Apr 07, 2023) | ||
| 17-66302958-A-G | Uncertain significance (Apr 01, 2024) | |||
| 17-66496274-C-T | PRKCA-related disorder | Likely benign (Mar 25, 2019) | ||
| 17-66641453-G-A | Benign (Dec 31, 2019) | |||
| 17-66641454-A-G | not specified | Uncertain significance (Jun 21, 2021) | ||
| 17-66645387-C-T | Likely benign (Feb 16, 2018) | |||
| 17-66645390-T-C | PRKCA-related disorder | Likely benign (Jul 19, 2019) | ||
| 17-66645466-A-G | not specified | Uncertain significance (Jan 26, 2023) | ||
| 17-66687137-A-G | not specified | Uncertain significance (Dec 16, 2023) | ||
| 17-66687189-A-G | not specified | Uncertain significance (May 09, 2023) | ||
| 17-66687243-C-T | not specified | Uncertain significance (Mar 29, 2023) | ||
| 17-66688414-A-T | not specified | Uncertain significance (Jan 11, 2023) | ||
| 17-66688430-G-C | not specified | Uncertain significance (Apr 04, 2023) | ||
| 17-66688952-T-C | not specified | Uncertain significance (Nov 09, 2023) | ||
| 17-66688960-G-A | Benign (Jun 17, 2021) | |||
| 17-66688966-C-T | Benign (Dec 31, 2019) | |||
| 17-66688991-G-A | not specified | Uncertain significance (Jun 24, 2022) | ||
| 17-66732738-C-T | Benign (May 16, 2018) | |||
| 17-66732747-A-G | Likely benign (Dec 31, 2019) | |||
| 17-66738796-C-T | Likely benign (Oct 10, 2018) | |||
| 17-66741709-G-C | not specified | Uncertain significance (Oct 28, 2023) | ||
| 17-66742638-A-G | Uncertain significance (Jan 14, 2022) | |||
| 17-66742640-C-T | Likely benign (Jun 29, 2018) | |||
| 17-66742701-A-G | Likely benign (Jun 01, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKCA | protein_coding | protein_coding | ENST00000413366 | 17 | 508108 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.368 | 0.632 | 125724 | 0 | 24 | 125748 | 0.0000954 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.22 | 213 | 392 | 0.543 | 0.0000214 | 4498 |
| Missense in Polyphen | 47 | 151.73 | 0.30976 | 1802 | ||
| Synonymous | -0.121 | 158 | 156 | 1.01 | 0.0000101 | 1194 |
| Loss of Function | 4.52 | 9 | 39.8 | 0.226 | 0.00000221 | 441 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000869 | 0.0000869 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.000278 | 0.000277 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000658 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)- dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B- ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF- kappa-B-induced genes, through IL1A-dependent induction of NF- kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O- tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. {ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Long-term depression - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Gap junction - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Axon guidance - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Leukocyte transendothelial migration - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;VEGF Signaling Pathway;Fc Epsilon Receptor I Signaling in Mast Cells;EGF-Ncore;Target Of Rapamycin (TOR) Signaling;Angiogenesis overview;miRs in Muscle Cell Differentiation;Follicle Stimulating Hormone (FSH) signaling pathway;Regulation of Microtubule Cytoskeleton;Endothelin Pathways;Signaling Pathways in Glioblastoma;Pathogenic Escherichia coli infection;AGE-RAGE pathway;Corticotropin-releasing hormone signaling pathway;Oncostatin M Signaling Pathway;Spinal Cord Injury;Alpha 6 Beta 4 signaling pathway;T-Cell Receptor and Co-stimulatory Signaling;Common Pathways Underlying Drug Addiction;Cardiac Hypertrophic Response;Human Complement System;Myometrial Relaxation and Contraction Pathways;Transcriptional activation by NRF2;Kit receptor signaling pathway;Focal Adhesion;Melatonin metabolism and effects;G Protein Signaling Pathways;Wnt Signaling Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;PDGFR-beta pathway;Wnt Signaling Pathway and Pluripotency;PI3K-Akt Signaling Pathway;Ras Signaling;Wnt Signaling Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;Calcium Regulation in the Cardiac Cell;ErbB Signaling Pathway;SHC1 events in ERBB2 signaling;Developmental Biology;Signaling by GPCR;Regulation of Ras family activation;Signaling by WNT;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;ionomycin and phorbal ester signaling pathway;bioactive peptide induced signaling pathway;links between pyk2 and map kinases;oxidative stress induced gene expression via nrf2;telomeres telomerase cellular aging and immortality;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;aspirin blocks signaling pathway involved in platelet activation;egf signaling pathway;transcription factor creb and its extracellular signals;regulation of eif-4e and p70s6 kinase;nitric oxide signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;role of mef2d in t-cell apoptosis;phospholipids as signalling intermediaries;cadmium induces dna synthesis and proliferation in macrophages;ccr3 signaling in eosinophils;vegf hypoxia and angiogenesis;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;VEGFA-VEGFR2 Pathway;effects of calcineurin in keratinocyte differentiation;signaling pathway from g-protein families;thrombin signaling and protease-activated receptors;g-secretase mediated erbb4 signaling pathway;cbl mediated ligand-induced downregulation of egf receptors pathway;attenuation of gpcr signaling;trka receptor signaling pathway;t cell receptor signaling pathway;bcr signaling pathway;keratinocyte differentiation;Alpha6Beta4Integrin;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;Extracellular matrix organization;Metabolism of RNA;Metabolism;Ghrelin;Calmodulin induced events;CaM pathway;KitReceptor;ATF-2 transcription factor network;Acetylcholine regulates insulin secretion;Regulation of insulin secretion;Neuronal System;CRH;pdgf signaling pathway;activation of pkc through g-protein coupled receptors;Disinhibition of SNARE formation;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;IL-7 signaling;Regulation of KIT signaling;tpo signaling pathway;WNT5A-dependent internalization of FZD4;PCP/CE pathway;ROBO receptors bind AKAP5;EGFR1;Ras signaling in the CD4+ TCR pathway;growth hormone signaling pathway;Ca2+ pathway;Beta-catenin independent WNT signaling;ErbB1 downstream signaling;fmlp induced chemokine gene expression in hmc-1 cells;Hemostasis;DAG and IP3 signaling;HuR (ELAVL1) binds and stabilizes mRNA;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;EGFR Transactivation by Gastrin;IL11;EPO signaling;Depolymerisation of the Nuclear Lamina;Nuclear Envelope Breakdown;Mitotic Prophase;Signaling events regulated by Ret tyrosine kinase;IL3;a6b1 and a6b4 Integrin signaling;Gastrin;Signaling by ROBO receptors;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;Signaling by VEGF;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Ca-dependent events;PLC beta mediated events;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Syndecan interactions;G-protein mediated events;Non-integrin membrane-ECM interactions;Opioid Signalling;G alpha (i) signalling events;RET signaling;Axon guidance;M Phase;G alpha (z) signalling events;Signaling by SCF-KIT;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;Signaling by ERBB2;Cell Cycle;Wnt;TNFalpha;Regulation of mRNA stability by proteins that bind AU-rich elements;Signaling by Receptor Tyrosine Kinases;Integration of energy metabolism;VEGF;Cell Cycle, Mitotic;Gastrin-CREB signalling pathway via PKC and MAPK;G alpha (q) signalling events;GPCR downstream signalling;Canonical NF-kappaB pathway;Intracellular signaling by second messengers;mTOR signaling pathway;PAR1-mediated thrombin signaling events;Downstream signaling in naïve CD8+ T cells;IL8- and CXCR1-mediated signaling events;Retinoic acid receptors-mediated signaling;TCR signaling in naïve CD8+ T cells;Role of Calcineurin-dependent NFAT signaling in lymphocytes;PDGFR-beta signaling pathway;Syndecan-4-mediated signaling events;Endothelins;IL8- and CXCR2-mediated signaling events;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;VEGFR1 specific signals;VEGFR2 mediated cell proliferation
(Consensus)
Recessive Scores
- pRec
- 0.856
Intolerance Scores
- loftool
- 0.298
- rvis_EVS
- -0.33
- rvis_percentile_EVS
- 30.7
Haploinsufficiency Scores
- pHI
- 0.810
- hipred
- Y
- hipred_score
- 0.790
- ghis
- 0.581
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkca
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- prkcaa
- Affected structure
- thrombocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- angiogenesis;positive regulation of endothelial cell proliferation;desmosome assembly;protein phosphorylation;mitotic nuclear envelope disassembly;cell adhesion;axon guidance;positive regulation of endothelial cell migration;positive regulation of cardiac muscle hypertrophy;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;platelet activation;positive regulation of cell migration;positive regulation of lipopolysaccharide-mediated signaling pathway;negative regulation of glial cell apoptotic process;histone H3-T6 phosphorylation;intracellular signal transduction;ERBB2 signaling pathway;regulation of mRNA stability;positive regulation of blood vessel endothelial cell migration;positive regulation of macrophage differentiation;positive regulation of angiogenesis;positive regulation of bone resorption;positive regulation of cell adhesion;positive regulation of mitotic cell cycle;regulation of insulin secretion;positive regulation of ERK1 and ERK2 cascade;response to interleukin-1;regulation of platelet aggregation;apoptotic signaling pathway;positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway;positive regulation of dense core granule biogenesis
- Cellular component
- nucleoplasm;cytoplasm;mitochondrion;endoplasmic reticulum;cytosol;plasma membrane;mitochondrial membrane;alphav-beta3 integrin-PKCalpha complex;perinuclear region of cytoplasm;extracellular exosome
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein kinase C activity;calcium-dependent protein kinase C activity;integrin binding;protein binding;ATP binding;zinc ion binding;enzyme binding;histone kinase activity (H3-T6 specific)