PRKCB
protein kinase C beta, the group of AGC family kinases|C2 domain containing protein kinases|MicroRNA protein coding host genes
Basic information
Region (hg38): 16:23835983-24220611
Previous symbols: [ "PRKCB2", "PKCB", "PRKCB1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKCB 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 | 22 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 2 | ||||
| non coding | 1 | |||||
| Total | 0 | 0 | 22 | 8 | 5 |
Variants in PRKCB
This is a list of pathogenic ClinVar variants found in the PRKCB region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 16-23836191-G-A | not specified | Uncertain significance (Oct 04, 2022) | ||
| 16-23836216-A-T | not specified | Uncertain significance (Aug 28, 2021) | ||
| 16-23836262-G-A | Benign/Likely benign (Aug 01, 2023) | |||
| 16-23836270-A-T | not specified | Uncertain significance (Jun 07, 2023) | ||
| 16-23836315-C-T | not specified | Uncertain significance (Nov 27, 2023) | ||
| 16-23836337-C-T | Benign (May 08, 2018) | |||
| 16-23988577-G-T | Progressive sensorineural hearing impairment | Pathogenic (Feb 12, 2016) | ||
| 16-23988588-G-T | not specified | Uncertain significance (Jun 16, 2024) | ||
| 16-24032170-C-T | not specified | Uncertain significance (Oct 26, 2022) | ||
| 16-24032175-T-G | not specified | Uncertain significance (Aug 20, 2024) | ||
| 16-24035424-A-G | not specified | Uncertain significance (Sep 01, 2021) | ||
| 16-24035494-G-A | not specified | Uncertain significance (Jul 30, 2024) | ||
| 16-24035523-G-A | not specified | Uncertain significance (May 17, 2023) | ||
| 16-24035531-C-T | Likely benign (Mar 01, 2023) | |||
| 16-24035532-G-A | not specified | Uncertain significance (Oct 01, 2024) | ||
| 16-24035540-T-C | Benign (Dec 31, 2019) | |||
| 16-24092867-C-T | PRKCB-related disorder | Benign (Sep 04, 2019) | ||
| 16-24094178-G-A | Benign (Jun 10, 2018) | |||
| 16-24094190-A-G | PRKCB-related disorder | Benign (Aug 11, 2024) | ||
| 16-24113044-A-G | PRKCB-related disorder | Likely benign (Jun 22, 2023) | ||
| 16-24123866-C-T | not specified | Uncertain significance (Apr 27, 2023) | ||
| 16-24123896-A-G | not specified | Uncertain significance (Feb 12, 2024) | ||
| 16-24123897-A-G | PRKCB-related disorder | Likely benign (Jan 03, 2024) | ||
| 16-24123911-G-C | PRKCB-related disorder | Conflicting classifications of pathogenicity (Sep 25, 2023) | ||
| 16-24123923-G-A | not specified | Uncertain significance (Dec 21, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKCB | protein_coding | protein_coding | ENST00000303531 | 17 | 384611 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000191 | 125723 | 0 | 2 | 125725 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.99 | 182 | 409 | 0.445 | 0.0000235 | 4509 |
| Missense in Polyphen | 29 | 138.62 | 0.2092 | 1496 | ||
| Synonymous | 0.300 | 154 | 159 | 0.970 | 0.00000986 | 1198 |
| Loss of Function | 5.62 | 0 | 36.8 | 0.00 | 0.00000184 | 432 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000654 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1- MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. {ECO:0000250, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790}.;
- Pathway
- 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);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);B cell receptor 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);Insulin resistance - 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);Carbohydrate digestion and absorption - Homo sapiens (human);Gap junction - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - 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);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);Leishmaniasis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Amphetamine addiction - 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);NF-kappa B 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;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;miRs in Muscle Cell Differentiation;Signaling Pathways in Glioblastoma;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Corticotropin-releasing hormone signaling pathway;Oncostatin M Signaling Pathway;Common Pathways Underlying Drug Addiction;Serotonin and anxiety;Myometrial Relaxation and Contraction Pathways;Kit receptor signaling pathway;Focal Adhesion;G Protein Signaling Pathways;Wnt Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Serotonin and anxiety-related events;PDGFR-beta pathway;Wnt Signaling Pathway and Pluripotency;Transcriptional regulation by RUNX1;Ras Signaling;Wnt Signaling Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Regulation of Ras family activation;Signaling by WNT;Signal Transduction;Gene expression (Transcription);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;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;Generic Transcription Pathway;B cell receptor signaling;GPCR GroupI metabotropic glutamate receptor;Activation of NF-kappaB in B cells;Signaling by the B Cell Receptor (BCR);GPCR signaling-G alpha q;RNA Polymerase II Transcription;Immune System;Ghrelin;Adaptive Immune System;KitReceptor;Downstream signaling events of B Cell Receptor (BCR);Neuronal System;BCR;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;tpo signaling pathway;fc epsilon receptor i signaling in mast cells;WNT5A-dependent internalization of FZD4;PCP/CE pathway;EGFR1;Ras signaling in the CD4+ TCR pathway;growth hormone signaling pathway;Beta-catenin independent WNT signaling;fmlp induced chemokine gene expression in hmc-1 cells;Hemostasis;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;IL11;EPO signaling;Depolymerisation of the Nuclear Lamina;Nuclear Envelope Breakdown;Mitotic Prophase;IL3;IL2-mediated signaling events;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;Signaling by VEGF;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;M Phase;G alpha (z) signalling events;RUNX1 regulates transcription of genes involved in differentiation of myeloid cells;Cell Cycle;Wnt;Signaling by Receptor Tyrosine Kinases;VEGF;Cell Cycle, Mitotic;GPCR downstream signalling;Transcriptional regulation by RUNX1;PAR1-mediated thrombin signaling events;Downstream signaling in naïve CD8+ T cells;Fc-epsilon receptor I signaling in mast cells;IL8- and CXCR1-mediated signaling events;TCR signaling in naïve CD8+ T cells;JNK signaling in the CD4+ TCR pathway;Role of Calcineurin-dependent NFAT signaling in lymphocytes;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
- 0.683
Intolerance Scores
- loftool
- 0.101
- rvis_EVS
- -0.8
- rvis_percentile_EVS
- 12.24
Haploinsufficiency Scores
- pHI
- 0.977
- hipred
- Y
- hipred_score
- 0.739
- ghis
- 0.599
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.866
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkcb
- 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- prkcbb
- Affected structure
- thrombocyte
- Phenotype tag
- abnormal
- Phenotype quality
- cellular adhesivity
Gene ontology
- Biological process
- adaptive immune response;regulation of transcription by RNA polymerase II;protein phosphorylation;calcium ion transport;cellular calcium ion homeostasis;apoptotic process;mitotic nuclear envelope disassembly;signal transduction;negative regulation of glucose transmembrane transport;peptidyl-serine phosphorylation;platelet activation;positive regulation of vascular endothelial growth factor receptor signaling pathway;histone H3-T6 phosphorylation;intracellular signal transduction;B cell activation;lipoprotein transport;positive regulation of I-kappaB kinase/NF-kappaB signaling;regulation of myeloid cell differentiation;positive regulation of angiogenesis;negative regulation of insulin receptor signaling pathway;B cell receptor signaling pathway;positive regulation of B cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;cellular response to carbohydrate stimulus;presynaptic modulation of chemical synaptic transmission;positive regulation of nucleic acid-templated transcription;regulation of synaptic vesicle exocytosis
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;calyx of Held;extracellular exosome;presynaptic cytosol
- Molecular function
- chromatin binding;protein serine/threonine kinase activity;protein kinase C activity;calcium-dependent protein kinase C activity;protein kinase C binding;calcium channel regulator activity;protein binding;ATP binding;zinc ion binding;nuclear receptor transcription coactivator activity;histone kinase activity (H3-T6 specific);histone binding;androgen receptor binding