PRKCZ
protein kinase C zeta, the group of AGC family kinases
Basic information
Region (hg38): 1:2050411-2185395
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 PRKCZ 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 | 5 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 2 | |||||
| Total | 0 | 0 | 5 | 3 | 4 |
Variants in PRKCZ
This is a list of pathogenic ClinVar variants found in the PRKCZ region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-2055515-G-A | Benign (May 18, 2018) | |||
| 1-2056556-A-G | not specified | Uncertain significance (Sep 16, 2021) | ||
| 1-2135276-C-T | not specified | Uncertain significance (Nov 09, 2021) | ||
| 1-2148890-C-G | not specified | Uncertain significance (Jul 14, 2021) | ||
| 1-2150781-C-T | Benign (Jan 22, 2018) | |||
| 1-2150864-A-G | Likely benign (Aug 16, 2018) | |||
| 1-2150880-C-T | Uncertain significance (Mar 06, 2018) | |||
| 1-2172067-C-G | Benign (Jul 16, 2018) | |||
| 1-2173976-C-T | Likely benign (Jun 01, 2023) | |||
| 1-2175249-G-A | not specified | Uncertain significance (Jul 14, 2021) | ||
| 1-2184675-C-G | Likely benign (Jul 01, 2022) | |||
| 1-2184994-C-T | Benign (Dec 31, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKCZ | protein_coding | protein_coding | ENST00000378567 | 18 | 134926 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.541 | 0.459 | 125683 | 0 | 65 | 125748 | 0.000258 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.80 | 224 | 377 | 0.594 | 0.0000250 | 3943 |
| Missense in Polyphen | 51 | 150.99 | 0.33776 | 1557 | ||
| Synonymous | 0.292 | 160 | 165 | 0.971 | 0.0000133 | 1084 |
| Loss of Function | 4.18 | 7 | 32.9 | 0.213 | 0.00000140 | 389 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000845 | 0.000843 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000654 | 0.000653 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.000247 | 0.000246 |
| Middle Eastern | 0.000654 | 0.000653 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro (PubMed:17313651). {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:18321849, ECO:0000269|PubMed:9447975}.;
- Pathway
- Platelet activation - Homo sapiens (human);Relaxin 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);Endocytosis - Homo sapiens (human);Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;VEGF Signaling Pathway;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Type II diabetes mellitus;IL-1 signaling pathway;miRs in Muscle Cell Differentiation;Signaling Pathways in Glioblastoma;TNF alpha Signaling Pathway;AGE-RAGE pathway;Allograft Rejection;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Interleukin-1 Induced Activation of NF-kappa-B;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;HDAC6 interactions;Wnt Signaling Pathway and Pluripotency;Prader-Willi and Angelman Syndrome;Splicing factor NOVA regulated synaptic proteins;EGF-EGFR Signaling Pathway;Insulin Signaling;Calcium Regulation in the Cardiac Cell;Regulation of Ras family activation;RAGE;Signal Transduction;VEGFA-VEGFR2 Pathway;phosphoinositides and their downstream targets;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;IL-7 signaling;EGFR1;CXCR4-mediated signaling events;ErbB1 downstream signaling;Hemostasis;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;IL2;Noncanonical Wnt signaling pathway;EPO signaling;Signaling by VEGF;IL4;TNFalpha;Signaling by Receptor Tyrosine Kinases;Signaling by TGF-beta Receptor Complex;VEGF;Signaling by TGF-beta family members;Insulin Pathway;Neurotrophic factor-mediated Trk receptor signaling;TNF receptor signaling pathway ;CDC42 signaling events;Insulin-mediated glucose transport;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);IL2 signaling events mediated by PI3K;p75(NTR)-mediated signaling;IGF1 pathway;Role of Calcineurin-dependent NFAT signaling in lymphocytes;IL1-mediated signaling events;Nephrin/Neph1 signaling in the kidney podocyte;Ceramide signaling pathway;TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition);RhoA signaling pathway;VEGFR2 mediated cell proliferation
(Consensus)
Recessive Scores
- pRec
- 0.448
Intolerance Scores
- loftool
- 0.375
- rvis_EVS
- -0.98
- rvis_percentile_EVS
- 8.85
Haploinsufficiency Scores
- pHI
- 0.193
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.685
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkcz
- Phenotype
- vision/eye phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; hematopoietic system phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- prkcz
- Affected structure
- dorsal longitudinal anastomotic vessel
- Phenotype tag
- abnormal
- Phenotype quality
- aplastic
Gene ontology
- Biological process
- microtubule cytoskeleton organization;positive regulation of cell-matrix adhesion;protein phosphorylation;inflammatory response;signal transduction;transforming growth factor beta receptor signaling pathway;long-term memory;positive regulation of cell population proliferation;cell migration;peptidyl-serine phosphorylation;establishment of cell polarity;negative regulation of protein complex assembly;activation of phospholipase D activity;activation of protein kinase B activity;positive regulation of interleukin-4 production;cellular response to insulin stimulus;intracellular signal transduction;negative regulation of apoptotic process;positive regulation of T-helper 2 cell differentiation;negative regulation of insulin receptor signaling pathway;positive regulation of insulin receptor signaling pathway;vesicle transport along microtubule;negative regulation of peptidyl-tyrosine phosphorylation;positive regulation of NF-kappaB transcription factor activity;protein heterooligomerization;negative regulation of hydrolase activity;membrane depolarization;membrane hyperpolarization;long-term synaptic potentiation;positive regulation of ERK1 and ERK2 cascade;protein kinase C signaling;protein localization to plasma membrane;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane;neuron projection extension;positive regulation of excitatory postsynaptic potential;positive regulation of T-helper 2 cell cytokine production;positive regulation of interleukin-5 secretion;positive regulation of interleukin-13 secretion;positive regulation of interleukin-10 secretion
- Cellular component
- stress fiber;nuclear envelope;cytoplasm;endosome;microtubule organizing center;cytosol;plasma membrane;cell-cell junction;bicellular tight junction;postsynaptic density;membrane;apical plasma membrane;nuclear matrix;cell junction;cell leading edge;vesicle;protein-containing complex;myelin sheath abaxonal region;axon hillock;membrane raft;apical cortex;perinuclear region of cytoplasm;extracellular exosome;Schaffer collateral - CA1 synapse;glutamatergic synapse
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein kinase C activity;protein binding;ATP binding;potassium channel regulator activity;protein kinase binding;protein domain specific binding;phospholipase binding;insulin receptor substrate binding;metal ion binding;14-3-3 protein binding