PRKCZ

Chr 1

protein kinase C zeta

Also known as: PKC-ZETA, PKC2

Protein kinase C zeta is a calcium-independent serine/threonine kinase that functions in PI3K and MAP kinase signaling pathways, regulating cell proliferation, polarity, inflammatory responses, and neuronal processes including long-term potentiation. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay, with onset typically in infancy. The gene shows significant constraint against loss-of-function variants (LOEUF 0.4), indicating intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
17
Pubs (1 yr)
141
P/LP submissions
P/LP missense
0.40
LOEUF
Mechanism
Clinical SummaryPRKCZ
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.54) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
134 unique Pathogenic / Likely Pathogenic· 37 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.541
Z-score 4.18
OE 0.21 (0.120.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.80Z-score
OE missense 0.59 (0.530.66)
224 obs / 377.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.120.40)
00.351.4
Missense OE0.59 (0.530.66)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 7 / 32.9Missense obs/exp: 224 / 377.3Syn Z: 0.29

ClinVar Variant Classifications

199 submitted variants in ClinVar

Classification Summary

Pathogenic127
Likely Pathogenic7
VUS37
Likely Benign7
Benign4
127
Pathogenic
7
Likely Pathogenic
37
VUS
7
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
127
Likely Pathogenic
7
VUS
37
Likely Benign
7
Benign
4
Total182

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRKCZ · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC