PRKCB

Chr 16

protein kinase C beta

Also known as: PKC-beta, PKCB, PKCI(2), PKCbeta, PRKCB1, PRKCB2

NCBI Gene: 5579 ENSG00000166501 UniProt: P05771 OMIM: 176970

The protein kinase C beta (PRKCB) gene encodes a calcium-activated serine/threonine kinase that regulates B-cell receptor signaling, insulin signaling, glucose transport, and endothelial cell function. This gene is extremely intolerant to loss-of-function variants (pLI near 1.0, LOEUF 0.081), but no specific Mendelian disease has been definitively associated with PRKCB mutations in humans. The high constraint scores suggest that mutations would likely be pathogenic if identified, but the inheritance pattern and clinical phenotype remain to be established.

OMIM ResearchSummary from RefSeq, 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 family members 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 a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.08

Clinical Summary— PRKCB

⚡

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

1 unique Pathogenic / Likely Pathogenic· 43 VUS of 81 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.08LOEUF

pLI 1.000

Z-score 5.62

OE 0.00 (0.00–0.08)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.99Z-score

OE missense 0.45 (0.39–0.50)

182 obs / 408.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.08)

0≤0.351.4

Missense OE?0.45 (0.39–0.50)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 0 / 36.8Missense obs/exp: 182 / 408.9Syn Z: 0.30

This gene — mechanism propensity

0.4189th %ile

GOF

0.5758th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

81 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS43

Likely Benign8

Benign8

Conflicting1

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	43	0	0	43
Likely Benign	0	1	0	7	8
Benign	0	0	3	5	8
Conflicting	—				1
Total	0	45	3	12	61

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap PRKCB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →