PRKCE
protein kinase C epsilon, the group of AGC family kinases|C2 domain containing protein kinases
Basic information
Region (hg38): 2:45651344-46187990
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (11 variants)
- not provided (8 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKCE 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 | 4 | |||||
| missense | 12 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | ||||
| non coding ? | 0 | |||||
| Total | 1 | 0 | 12 | 2 | 4 |
Variants in PRKCE
This is a list of pathogenic ClinVar variants found in the PRKCE region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-45652107-G-C | not specified | Uncertain significance (Jan 26, 2023) | ||
| 2-45843021-AGAGTGTATGTGATCATC-A | Uncertain significance (Dec 08, 2022) | |||
| 2-45976465-G-A | not specified | Uncertain significance (Nov 27, 2023) | ||
| 2-45976482-C-A | Likely benign (Dec 31, 2018) | |||
| 2-45984593-G-A | not specified | Uncertain significance (Jul 20, 2021) | ||
| 2-46001554-G-A | Benign (Jul 01, 2022) | |||
| 2-46007479-A-G | not specified | Uncertain significance (Apr 12, 2022) | ||
| 2-46007492-A-C | not specified | Uncertain significance (Sep 27, 2021) | ||
| 2-46007502-A-G | Benign (Dec 31, 2019) | |||
| 2-46007504-T-A | not specified | Uncertain significance (Dec 19, 2022) | ||
| 2-46007549-G-C | not specified | Uncertain significance (Oct 06, 2021) | ||
| 2-46007564-C-G | not specified | Uncertain significance (Jun 12, 2023) | ||
| 2-46007602-C-T | not specified | Uncertain significance (Feb 15, 2023) | ||
| 2-46010391-G-A | Benign (Dec 31, 2019) | |||
| 2-46010445-A-G | Benign (Dec 31, 2019) | |||
| 2-46086231-A-T | not specified | Uncertain significance (Jan 31, 2024) | ||
| 2-46086289-C-A | not specified | Uncertain significance (Sep 27, 2022) | ||
| 2-46086299-G-A | Likely benign (May 01, 2023) | |||
| 2-46086303-C-G | See cases | Uncertain significance (Dec 02, 2019) | ||
| 2-46086305-A-G | not specified | Uncertain significance (Jun 29, 2023) | ||
| 2-46151104-G-A | Pathogenic (Nov 01, 2019) | |||
| 2-46151202-C-A | not specified | Uncertain significance (Apr 25, 2023) | ||
| 2-46159645-G-A | Benign (Dec 31, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKCE | protein_coding | protein_coding | ENST00000306156 | 15 | 536646 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000124 | 118851 | 0 | 5 | 118856 | 0.0000210 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.77 | 231 | 458 | 0.504 | 0.0000270 | 4872 |
| Missense in Polyphen | 42 | 185.62 | 0.22627 | 2024 | ||
| Synonymous | -0.0589 | 184 | 183 | 1.01 | 0.0000118 | 1377 |
| Loss of Function | 5.33 | 3 | 38.8 | 0.0773 | 0.00000195 | 435 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000664 | 0.0000652 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000856 | 0.0000856 |
| European (Non-Finnish) | 0.0000359 | 0.0000268 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F- actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL- mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Insulin resistance - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Tight junction - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;VEGF Signaling Pathway;Physiological and Pathological Hypertrophy of the Heart;miRs in Muscle Cell Differentiation;Oncostatin M Signaling Pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;VEGFA-VEGFR2 Signaling Pathway;Wnt Signaling Pathway and Pluripotency;Calcium Regulation in the Cardiac Cell;SHC1 events in ERBB2 signaling;Signaling by GPCR;Regulation of Ras family activation;Signal Transduction;cardiac protection against ros;protein kinase a at the centrosome;phosphoinositides and their downstream targets;keratinocyte differentiation;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;Ghrelin;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;IL-7 signaling;Hemostasis;DAG and IP3 signaling;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;EPO signaling;IL2-mediated signaling events;G alpha (z) signalling events;Leptin;Signaling by ERBB2;Signaling by Receptor Tyrosine Kinases;VEGF;G alpha (q) signalling events;GPCR downstream signalling;Intracellular signaling by second messengers;LPA4-mediated signaling events;LPA receptor mediated events;CDC42 signaling events;Downstream signaling in naïve CD8+ T cells;IL8- and CXCR1-mediated signaling events;TCR signaling in naïve CD8+ T cells;Role of Calcineurin-dependent NFAT signaling in lymphocytes;PDGFR-beta signaling pathway;Endothelins;TCR signaling in naïve CD4+ T cells
(Consensus)
Recessive Scores
- pRec
- 0.778
Intolerance Scores
- loftool
- 0.0209
- rvis_EVS
- -0.02
- rvis_percentile_EVS
- 52.09
Haploinsufficiency Scores
- pHI
- 0.881
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.550
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkce
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; 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); hematopoietic system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype;
Zebrafish Information Network
- Gene name
- prkceb
- Affected structure
- pronephric glomerulus
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- macrophage activation involved in immune response;protein phosphorylation;apoptotic process;cell cycle;cell adhesion;signal transduction;positive regulation of epithelial cell migration;positive regulation of fibroblast migration;positive regulation of cell-substrate adhesion;peptidyl-serine phosphorylation;platelet activation;positive regulation of actin filament polymerization;negative regulation of protein ubiquitination;lipopolysaccharide-mediated signaling pathway;positive regulation of insulin secretion;positive regulation of synaptic transmission, GABAergic;positive regulation of cytokinesis;intracellular signal transduction;locomotory exploration behavior;TRAM-dependent toll-like receptor 4 signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of catalytic activity;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to morphine;positive regulation of MAPK cascade;regulation of peptidyl-tyrosine phosphorylation;positive regulation of lipid catabolic process;release of sequestered calcium ion into cytosol;regulation of release of sequestered calcium ion into cytosol;cell division;regulation of insulin secretion involved in cellular response to glucose stimulus;positive regulation of mucus secretion;cellular response to ethanol;cellular response to prostaglandin E stimulus;cellular response to hypoxia;positive regulation of wound healing;positive regulation of protein localization to plasma membrane;positive regulation of signaling receptor activity;negative regulation of sodium ion transmembrane transporter activity;positive regulation of cellular glucuronidation
- Cellular component
- nucleus;cytoplasm;mitochondrion;endoplasmic reticulum;Golgi apparatus;cytosol;cytoskeleton;plasma membrane;perinuclear region of cytoplasm;cell periphery
- Molecular function
- actin monomer binding;protein serine/threonine kinase activity;protein kinase C activity;calcium-independent protein kinase C activity;protein binding;ATP binding;enzyme activator activity;enzyme binding;receptor activator activity;ethanol binding;metal ion binding;14-3-3 protein binding