PRKCQ

protein kinase C theta, the group of AGC family kinases|C2 domain containing protein kinases

Basic information

Region (hg38): 10:6427142-6580301

Links

ENSG00000065675 ∙ NCBI:5588 ∙ OMIM:600448 ∙ HGNC:9410 ∙ Uniprot:Q04759 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRKCQ gene.

• Inborn genetic diseases (23 variants)
• not provided (4 variants)
• Inflammatory bowel disease 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKCQ 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					1	1
missense			23		3	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	0	4

Variants in PRKCQ

This is a list of pathogenic ClinVar variants found in the PRKCQ region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-6428225-C-T		not specified	Uncertain significance (Jan 23, 2023)
10-6428308-G-A		not specified	Uncertain significance (Jan 04, 2024)
10-6430871-C-T		not specified	Uncertain significance (Mar 03, 2022)
10-6430905-C-T		not specified	Uncertain significance (Jul 14, 2023)
10-6441955-G-C		not specified	Uncertain significance (Jun 17, 2022)
10-6442024-G-A		not specified	Uncertain significance (Dec 18, 2023)
10-6442078-A-C		not specified	Uncertain significance (Jul 14, 2022)
10-6456722-A-C		not specified	Uncertain significance (Nov 23, 2021)
10-6464322-G-C			Benign (Jul 23, 2018)
10-6464401-T-G		not specified	Uncertain significance (Apr 04, 2023)
10-6479019-C-T			Benign (Sep 12, 2018)
10-6479117-C-A		not specified	Uncertain significance (Feb 05, 2024)
10-6479123-T-C		not specified	Uncertain significance (Jul 15, 2021)
10-6479126-C-T		not specified	Uncertain significance (Apr 17, 2023)
10-6483484-C-T		not specified	Uncertain significance (Sep 12, 2023)
10-6483546-T-C		not specified	Uncertain significance (Jun 24, 2022)
10-6483556-T-C		not specified	Uncertain significance (Dec 20, 2023)
10-6483574-G-A		not specified	Uncertain significance (Aug 08, 2022)
10-6483589-T-C		not specified	Uncertain significance (Jan 09, 2024)
10-6485181-G-A		Inflammatory bowel disease 1	Benign (Apr 30, 2020)
10-6485209-G-T		not specified	Uncertain significance (Jul 20, 2021)
10-6485227-G-C		not specified	Uncertain significance (Jun 09, 2022)
10-6485251-T-C		not specified	Uncertain significance (Mar 01, 2024)
10-6497055-T-C			Benign (Mar 29, 2018)
10-6498527-T-A		not specified	Uncertain significance (Feb 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRKCQ	protein_coding	protein_coding	ENST00000263125	17	153159

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.297	0.703	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	283	419	0.676	0.0000242	4749
Missense in Polyphen		63	140.5	0.44839		1578
Synonymous	-0.230	162	158	1.02	0.0000102	1231
Loss of Function	4.69	10	43.3	0.231	0.00000248	477

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non- redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non- canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. {ECO:0000269|PubMed:11342610, ECO:0000269|PubMed:14988727, ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:16252004, ECO:0000269|PubMed:16356855, ECO:0000269|PubMed:16709830, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:8657160}.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Measles - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;VEGF Signaling Pathway;miRs in Muscle Cell Differentiation;Signaling Pathways in Glioblastoma;Corticotropin-releasing hormone signaling pathway;Vitamin D Receptor Pathway;Myometrial Relaxation and Contraction Pathways;MFAP5-mediated ovarian cancer cell motility and invasiveness;G Protein Signaling Pathways;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Wnt Signaling Pathway and Pluripotency;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Insulin Signaling;Calcium Regulation in the Cardiac Cell;T-Cell antigen Receptor (TCR) Signaling Pathway;Developmental Biology;Signaling by GPCR;Signal Transduction;Gene expression (Transcription);keratinocyte differentiation;Generic Transcription Pathway;Downstream TCR signaling;TCR signaling;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Fc epsilon receptor (FCERI) signaling;TCR;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Ghrelin;Programmed Cell Death;Adaptive Immune System;BCR;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;IL-7 signaling;Hemostasis;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;EPO signaling;Netrin-1 signaling;Gastrin;G alpha (i) signalling events;Axon guidance;G alpha (z) signalling events;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;FCERI mediated NF-kB activation;VEGF;G alpha (q) signalling events;GPCR downstream signalling;Transcriptional regulation by RUNX1;Downstream signaling in naïve CD8+ T cells;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;TCR signaling in naïve CD8+ T cells;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Endothelins;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.459

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

• pHI: 0.670
• hipred: Y
• hipred_score: 0.756
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.793

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prkcq
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; vision/eye phenotype; muscle 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); pigmentation phenotype; neoplasm; hematopoietic 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); reproductive 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); respiratory system phenotype; immune system phenotype

Gene ontology

• Biological process: regulation of cell growth;regulation of transcription, DNA-templated;membrane protein ectodomain proteolysis;inflammatory response;axon guidance;peptidyl-serine phosphorylation;platelet activation;positive regulation of telomere maintenance via telomerase;positive regulation of interleukin-17 production;positive regulation of interleukin-4 production;intracellular signal transduction;Fc-epsilon receptor signaling pathway;positive regulation of T cell proliferation;positive regulation of interleukin-2 biosynthetic process;regulation of megakaryocyte differentiation;negative regulation of insulin receptor signaling pathway;T cell receptor signaling pathway;positive regulation of T cell activation;positive regulation of NF-kappaB transcription factor activity;positive regulation of telomerase activity;cell chemotaxis;negative regulation of T cell apoptotic process;regulation of platelet aggregation;positive regulation of telomere capping;positive regulation of T-helper 17 type immune response;positive regulation of T-helper 2 cell activation
• Cellular component: immunological synapse;microtubule organizing center;cytosol;plasma membrane;aggresome
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein kinase C activity;protein binding;ATP binding;metal ion binding