PRKCG

Chr 19AD

protein kinase C gamma

Also known as: PKC-gamma, PKCC, PKCG, PKCI(3), PKCgamma, SCA14

NCBI Gene: 5582 ENSG00000126583 UniProt: P05129 OMIM: 176980

The protein kinase C gamma (PRKCG) encodes a brain-specific serine/threonine kinase that regulates neuronal receptors, synaptic plasticity, and cerebellar development through phosphorylation of key targets including glutamate receptors and p53. Mutations cause spinocerebellar ataxia 14 (SCA14), a progressive cerebellar degenerative disorder with autosomal dominant inheritance. PRKCG is highly constrained against loss-of-function mutations (pLI 0.999, LOEUF 0.203), reflecting its critical role in neuronal function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

ADLOEUF 0.201 OMIM phenotype

Clinical Summary— PRKCG

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 66 VUS of 97 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — PRKCG

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 5.28

OE 0.08 (0.04–0.20)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.06Z-score

OE missense 0.58 (0.52–0.64)

238 obs / 413.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.20)

0≤0.351.4

Missense OE?0.58 (0.52–0.64)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 3 / 38.3Missense obs/exp: 238 / 413.0Syn Z: -0.34

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic10

VUS66

Likely Benign10

Benign4

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	9	1	0	10
VUS	2	55	4	5	66
Likely Benign	0	0	3	7	10
Benign	0	1	2	1	4
Total	2	65	10	13	90

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

1 pathogenic / likely-pathogenic (of 3) ClinVar copy-number / structural variants overlap PRKCG — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →