GeneBe

PRKCI

protein-coding

protein kinase C iota, the group of AGC family kinases

Gene summary

This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]

Previous symbols:
  • DXS1179E

MANE transcript

NM_002740.6

Inheritance

—

ClinVar variants

U:63B:3

Top phenotype

PRKCI-related disorder

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr3:170,222,424-170,305,977

External References & Databases

Ensembl (ENSG00000163558)NCBI Gene (5584)OMIM (600539)HGNC:9404GenCCUniProt (P41743)AlphaFoldClinVar (PRKCI)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~83.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRKCI variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 43
PRKCI-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002740.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
3
clinvar
 6
missense
54
clinvar
 54
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total00633066
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002740.6RefSeqNP_002731.418MANE Select
ENST00000295797.5EnsemblENSP00000295797.418MANE Select
ENST00000904925.1EnsemblENSP00000574984.119Standard
ENST00000904925.2EnsemblENSP00000574984.119Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
prkciDanio rerio

Structure: neuroepithelial cell

Quality: broken

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Platelet activation - Homo sapiens (human)
  • Endocytosis - Homo sapiens (human)
  • Tight junction - Homo sapiens (human)
  • Hippo signaling pathway - Homo sapiens (human)
  • Rap1 signaling pathway - Homo sapiens (human)

Biological Process

  • protein phosphorylation
  • protein targeting to membrane
  • cytoskeleton organization
  • actin filament organization
  • positive regulation of neuron projection development

Molecular Function

  • protein kinase activity
  • protein serine/threonine kinase activity
  • protein kinase C activity
  • protein binding
  • ATP binding

Cellular Component

  • Golgi membrane
  • nucleus
  • nucleoplasm
  • endosome
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000295797
Coding exons
18
Length
83617
Individuals with no LoFs
125722
Homozygous LoFs
0
Heterozygous LoFs
26
Defined
125748
p
0.000103
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.791903330.5700.00001763978
Missense (PolyPhen)761740.436782073
Synonymous-0.7171151061.090.000005141058
Loss of Function4.271038.60.2590.00000222428

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.0000320.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000220.00022rare
Finnish0.000140.00014rare
European (Non-Finnish)0.0000790.000079rare
South Asian0.0000980.000098rare
Other0.000340.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non- small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. {ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}.;

Intolerance Scores

LoFtool
0.499
RVIS EVS
-0.89
RVIS percentile EVS
10.3

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.993

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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