PRKCD
protein kinase C delta, the group of C2 domain containing protein kinases|AGC family kinases
Basic information
Region (hg38): 3:53156009-53192717
Links
Phenotypes
GenCC
Source:
- autoimmune lymphoproliferative syndrome (Supportive), mode of inheritance: AD
- common variable immunodeficiency (Supportive), mode of inheritance: AD
- autosomal systemic lupus erythematosus type 16 (Supportive), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Autoimmune lymphoproliferative syndrome type III | AR | Allergy/Immunology/Infectious | Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; medical management (eg, with immunosuppressive agents) of autoimmune manifestations has been described as beneficial | Allergy/Immunology/Infectious | 23319571; 23430113; 23666743 |
ClinVar
This is a list of variants' phenotypes submitted to
- Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (5 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKCD 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 | 129 | 142 | ||||
| missense | 171 | 176 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| splice region | 13 | 18 | 2 | 33 | ||
| non coding | 82 | 46 | 130 | |||
| Total | 5 | 4 | 179 | 216 | 56 |
Highest pathogenic variant AF is 0.00000657
Variants in PRKCD
This is a list of pathogenic ClinVar variants found in the PRKCD region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-53178163-C-T | Benign (May 22, 2021) | |||
| 3-53178196-C-A | Benign (May 14, 2021) | |||
| 3-53178367-C-T | not specified | Benign (Nov 12, 2023) | ||
| 3-53178427-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Jun 20, 2022) | ||
| 3-53178428-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Feb 26, 2021) | ||
| 3-53178431-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Dec 07, 2023) | ||
| 3-53178443-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Jan 10, 2024) | ||
| 3-53178444-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Jun 23, 2018) | ||
| 3-53178452-C-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Apr 16, 2022) | ||
| 3-53178466-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Nov 27, 2021) | ||
| 3-53178466-G-C | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Aug 27, 2021) | ||
| 3-53178478-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Aug 30, 2021) | ||
| 3-53178479-C-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Dec 18, 2020) | ||
| 3-53178479-C-G | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Dec 31, 2019) | ||
| 3-53178479-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Feb 16, 2023) | ||
| 3-53178485-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Jun 02, 2020) | ||
| 3-53178486-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Nov 06, 2020) | ||
| 3-53178490-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD • Inborn genetic diseases | Conflicting classifications of pathogenicity (Jan 25, 2024) | ||
| 3-53178491-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Oct 25, 2023) | ||
| 3-53178509-C-T | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Jul 19, 2023) | ||
| 3-53178510-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Uncertain significance (Jul 18, 2023) | ||
| 3-53178512-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Oct 23, 2021) | ||
| 3-53178512-G-C | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Jan 08, 2021) | ||
| 3-53178515-G-C | Inborn genetic diseases | Uncertain significance (Feb 27, 2023) | ||
| 3-53178527-G-A | Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD | Likely benign (Nov 04, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKCD | protein_coding | protein_coding | ENST00000394729 | 17 | 36709 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000517 | 125743 | 0 | 3 | 125746 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.11 | 241 | 421 | 0.573 | 0.0000262 | 4525 |
| Missense in Polyphen | 80 | 201.72 | 0.39658 | 2127 | ||
| Synonymous | 1.22 | 150 | 170 | 0.881 | 0.0000119 | 1217 |
| Loss of Function | 5.31 | 2 | 36.8 | 0.0544 | 0.00000185 | 421 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| 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 contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor- initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self- antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)- induced inhibition of cell cycle progression at G1/S phase by up- regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro- survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl- phenylalanine (fMLP)-treated cells, is required for NCF1 (p47- phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C- terminal and regulates the interaction between MUC1 and beta- catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). {ECO:0000250, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500}.;
- Disease
- DISEASE: Autoimmune lymphoproliferative syndrome 3 (ALPS3) [MIM:615559]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity. {ECO:0000269|PubMed:23319571}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Neurotrophin signaling pathway - 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);GnRH signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;VEGF Signaling Pathway;Type II diabetes mellitus;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;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Alpha 6 Beta 4 signaling pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;IL-6 signaling pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Wnt Signaling Pathway and Pluripotency;EGF-EGFR Signaling Pathway;Insulin Signaling;Calcium Regulation in the Cardiac Cell;Type II interferon signaling (IFNG);T-Cell antigen Receptor (TCR) Signaling Pathway;SHC1 events in ERBB2 signaling;Signaling by GPCR;RAGE;Neutrophil degranulation;Signal Transduction;hiv-1 nef: negative effector of fas and tnf;VEGFA-VEGFR2 Pathway;keratinocyte differentiation;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;Metabolism of RNA;TCR;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Ghrelin;FGF;Programmed Cell Death;Calmodulin induced events;CaM pathway;Fibroblast growth factor-1;BCR;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;IL-7 signaling;EGFR1;ErbB1 downstream signaling;Hemostasis;DAG and IP3 signaling;Validated transcriptional targets of TAp63 isoforms;HuR (ELAVL1) binds and stabilizes mRNA;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;NGF;EPO signaling;Gastrin;Interferon gamma signaling;IFN-gamma pathway;Signaling by VEGF;Ca-dependent events;PLC beta mediated events;G-protein mediated events;IL4;Opioid Signalling;G alpha (i) signalling events;G alpha (z) signalling events;IL5;Leptin;Signaling by ERBB2;IL6;Wnt;TNFalpha;Regulation of mRNA stability by proteins that bind AU-rich elements;Signaling by Receptor Tyrosine Kinases;VEGF;G alpha (q) signalling events;GPCR downstream signalling;Intracellular signaling by second messengers;PAR1-mediated thrombin signaling events;LPA receptor mediated events;Interferon Signaling;IGF1 pathway;Alpha-synuclein signaling;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;Trk receptor signaling mediated by the MAPK pathway;Hedgehog signaling events mediated by Gli proteins;Syndecan-4-mediated signaling events;IL6-mediated signaling events;Endothelins;Signaling events mediated by VEGFR1 and VEGFR2;Ceramide signaling pathway;p53 pathway;Syndecan-2-mediated signaling events;VEGFR2 mediated cell proliferation
(Consensus)
Recessive Scores
- pRec
- 0.641
Intolerance Scores
- loftool
- 0.201
- rvis_EVS
- -1.04
- rvis_percentile_EVS
- 7.77
Haploinsufficiency Scores
- pHI
- 0.507
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.553
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.966
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkcd
- Phenotype
- liver/biliary system 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; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype;
Gene ontology
- Biological process
- stimulatory C-type lectin receptor signaling pathway;protein phosphorylation;apoptotic process;cell cycle;signal transduction;intrinsic apoptotic signaling pathway in response to oxidative stress;regulation of signaling receptor activity;immunoglobulin mediated immune response;histone phosphorylation;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;peptidyl-tyrosine phosphorylation;termination of signal transduction;platelet activation;negative regulation of actin filament polymerization;positive regulation of endodeoxyribonuclease activity;negative regulation of protein binding;activation of protein kinase activity;interleukin-10 production;interleukin-12 production;positive regulation of superoxide anion generation;regulation of actin cytoskeleton organization;negative regulation of glial cell apoptotic process;positive regulation of protein dephosphorylation;intracellular signal transduction;Fc-gamma receptor signaling pathway involved in phagocytosis;B cell proliferation;neutrophil activation;positive regulation of protein import into nucleus;defense response to bacterium;neutrophil degranulation;negative regulation of MAP kinase activity;regulation of mRNA stability;negative regulation of insulin receptor signaling pathway;negative regulation of inflammatory response;negative regulation of peptidyl-tyrosine phosphorylation;protein stabilization;negative regulation of filopodium assembly;cell chemotaxis;interferon-gamma-mediated signaling pathway;cellular response to hydrogen peroxide;cellular response to hydroperoxide;negative regulation of platelet aggregation;cellular senescence;positive regulation of phospholipid scramblase activity;cellular response to angiotensin;positive regulation of ceramide biosynthetic process;positive regulation of glucosylceramide catabolic process;positive regulation of sphingomyelin catabolic process;positive regulation of response to DNA damage stimulus;positive regulation of apoptotic signaling pathway
- Cellular component
- extracellular region;nucleus;nucleoplasm;cytoplasm;endoplasmic reticulum;cytosol;plasma membrane;cell-cell junction;nuclear matrix;azurophil granule lumen;perinuclear region of cytoplasm;extracellular exosome
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein kinase C activity;calcium-independent protein kinase C activity;non-membrane spanning protein tyrosine kinase activity;protein binding;ATP binding;enzyme activator activity;enzyme binding;kinase binding;protein kinase binding;insulin receptor substrate binding;metal ion binding