PRKCH
protein kinase C eta, the group of C2 domain containing protein kinases|AGC family kinases
Basic information
Region (hg38): 14:61187559-61550980
Previous symbols: [ "PRKCL" ]
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 PRKCH 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 | 2 | |||||
| missense | 33 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 2 | |||||
| Total | 0 | 0 | 34 | 2 | 2 |
Variants in PRKCH
This is a list of pathogenic ClinVar variants found in the PRKCH region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-61280106-C-T | not specified | Uncertain significance (May 01, 2024) | ||
| 14-61280116-G-T | not specified | Uncertain significance (Oct 25, 2022) | ||
| 14-61280133-A-T | not specified | Uncertain significance (Aug 28, 2024) | ||
| 14-61280216-C-T | not specified | Uncertain significance (Apr 19, 2024) | ||
| 14-61280236-G-T | not specified | Uncertain significance (Jun 29, 2023) | ||
| 14-61280250-T-G | not specified | Uncertain significance (Feb 28, 2024) | ||
| 14-61280256-C-T | not specified | Uncertain significance (Mar 01, 2023) | ||
| 14-61280304-C-A | not specified | Uncertain significance (Jul 19, 2023) | ||
| 14-61280312-G-A | EBV-positive nodal T- and NK-cell lymphoma | Likely benign (-) | ||
| 14-61280321-G-A | not specified | Uncertain significance (Aug 17, 2021) | ||
| 14-61280337-G-T | not specified | Uncertain significance (Dec 05, 2024) | ||
| 14-61280340-G-T | not specified | Uncertain significance (Jul 02, 2024) | ||
| 14-61280342-A-C | not specified | Uncertain significance (Dec 06, 2023) | ||
| 14-61280358-T-C | not specified | Uncertain significance (Sep 25, 2024) | ||
| 14-61280366-G-C | not specified | Uncertain significance (Mar 25, 2022) | ||
| 14-61280375-G-A | not specified | Uncertain significance (Oct 06, 2021) | ||
| 14-61280408-T-C | not specified | Uncertain significance (Aug 15, 2023) | ||
| 14-61280469-G-A | not specified | Uncertain significance (Jan 30, 2024) | ||
| 14-61280508-C-A | not specified | Uncertain significance (Apr 09, 2024) | ||
| 14-61280508-C-G | not specified | Uncertain significance (Dec 02, 2024) | ||
| 14-61280511-T-C | not specified | Uncertain significance (Feb 28, 2024) | ||
| 14-61280519-G-A | not specified | Uncertain significance (Mar 07, 2024) | ||
| 14-61280571-G-A | not specified | Uncertain significance (Sep 08, 2024) | ||
| 14-61280597-C-T | not specified | Uncertain significance (May 17, 2023) | ||
| 14-61280605-C-A | not specified | Uncertain significance (Oct 17, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKCH | protein_coding | protein_coding | ENST00000332981 | 14 | 363418 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.429 | 0.571 | 125735 | 0 | 12 | 125747 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.19 | 283 | 407 | 0.695 | 0.0000222 | 4531 |
| Missense in Polyphen | 75 | 163.54 | 0.45862 | 1862 | ||
| Synonymous | 0.0256 | 159 | 159 | 0.997 | 0.00000934 | 1292 |
| Loss of Function | 4.58 | 9 | 40.5 | 0.222 | 0.00000271 | 382 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000116 | 0.000116 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000165 | 0.000109 |
| Finnish | 0.0000463 | 0.0000462 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.000165 | 0.000109 |
| South Asian | 0.0000334 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1- dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}.;
- Disease
- DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269|PubMed:17206144}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;VEGF Signaling Pathway;miRs in Muscle Cell Differentiation;Signaling Pathways in Glioblastoma;Oncostatin M Signaling Pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Wnt Signaling Pathway and Pluripotency;Insulin Signaling;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;keratinocyte differentiation;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;IL-7 signaling;Hemostasis;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;EPO signaling;G alpha (z) signalling events;VEGF;G alpha (q) signalling events;GPCR downstream signalling;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Endothelins
(Consensus)
Recessive Scores
- pRec
- 0.291
Intolerance Scores
- loftool
- 0.272
- rvis_EVS
- -0.44
- rvis_percentile_EVS
- 24.46
Haploinsufficiency Scores
- pHI
- 0.460
- hipred
- Y
- hipred_score
- 0.792
- ghis
- 0.464
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkch
- Phenotype
- immune system phenotype; vision/eye phenotype; 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); neoplasm; homeostasis/metabolism phenotype; growth/size/body region phenotype; 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); endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- protein phosphorylation;signal transduction;positive regulation of macrophage derived foam cell differentiation;peptidyl-serine phosphorylation;platelet activation;negative regulation of glial cell apoptotic process;intracellular signal transduction;positive regulation of keratinocyte differentiation;positive regulation of B cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;positive regulation of glial cell proliferation;positive regulation of protein localization to plasma membrane;regulation of bicellular tight junction assembly
- Cellular component
- cytoplasm;cytosol;plasma membrane;extracellular exosome
- Molecular function
- protein serine/threonine kinase activity;protein kinase C activity;protein binding;ATP binding;enzyme binding;metal ion binding