PRKCA

Chr 17

protein kinase C alpha

Also known as: AAG6, PKC-alpha, PKCA, PKCI+/-, PKCalpha

NCBI Gene: 5578ENSG00000154229UniProt: P17252

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the 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 kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Pituitary tumor, invasive
0
Active trials
11
Pathogenic / LP
75
ClinVar variants
8
Pubs (1 yr)
3.2
Missense Z· constrained
0.40
LOEUF
Clinical Summary— PRKCA
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 43 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.40LOEUF
pLI 0.368
Z-score 4.52
OE 0.23 (0.14–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.22Z-score
OE missense 0.54 (0.48–0.61)
213 obs / 392.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.23 (0.14–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.48–0.61)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 9 / 39.8Missense obs/exp: 213 / 392.4Syn Z: -0.12

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS43
Likely Benign13
Benign8
10
Pathogenic
1
Likely Pathogenic
43
VUS
13
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
1
35
7
0
43
Likely Benign
0
2
2
9
13
Benign
0
0
2
6
8
Total137221575

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

View in ClinVar →

Protein Context — Lollipop Plot

PRKCA · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pituitary tumor, invasive

Molecular basis of disorder known

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Histologic and Genetic Features of 51 Melanocytic Neoplasms With Protein Kinase C Fusion Genes.
de la Fouchardière A et al.·Mod Pathol
2023
SNPs, adipokynes and adiposity in children with asthma.
Machado ME et al.·J Asthma
2023Review
Melanocytic Skin Neoplasms: What Lesson From Genomic Aberrations?
Urso C·Am J Dermatopathol
2019Review
Integrated network pharmacology, proteomics, molecular docking, and experiments in vivo and in vitro to explore the efficacy and potential mechanism of bufalin against hepatocellular carcinoma angiogenesis.
Li Y et al.·J Ethnopharmacol
2025Functional
[Chordoid glioma: a clinicopathological study].
Wang LM et al.·Zhonghua Bing Li Xue Za Zhi
2021
Papillary glioneuronal tumors: histological and molecular characteristics and diagnostic value of SLC44A1-PRKCA fusion.
Pages M et al.·Acta Neuropathol Commun
2015
Atypical defects resulting in growth hormone insensitivity.
Wit JM et al.·Growth Horm IGF Res
2016Review
Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma.
Guo Y et al.·Oncotarget
2017
Chemogenetic targeting TRPV1 in obesity-induced depression: Unveiling therapeutic potential of eicosapentaenoic acid and acupuncture.
Lin YW et al.·Brain Behav Immun
2025
Pharmacogenomics of Antihypertensive Drugs in Brazil: Recent Progress and Clinical Implications.
Vecchia Genvigir FD et al.·Endocr Metab Immune Disord Drug Targets
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The chordoid glioma PRKCA D463H mutation is a kinase inactive, gain-of-function allele that induces early-onset chondrosarcoma in mice.
Calleja V et al.·Sci Signal
2025Open Access
Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer Through Targeting Pre-miR-374b-PRKCA/HBP1 Axis.
Liu F et al.·Mol Carcinog
2025
Tensile stress promotes the chondrogenic ability of condylar cartilage stem/progenitor cells in the temporomandibular joint via the Piezo1-Ca2+-Prkca pathway.
Gong W et al.·Stem Cell Res Ther
2025Open Access
Knowledge-guided multi-level network modeling with experimental characterization identifies PRKCA as a novel biomarker and tumor suppressor triggering ferroptosis in prostate cancer.
Lin Y et al.·Brief Bioinform
2025Open AccessFunctional
Injectable sustainable andrographolide-releasing hydrogel for long-lasting alleviation of osteoarthritis and regulation of chondrocyte autophagy via PRKCA/EGFR.
Chen Y et al.·Mater Today Bio
2025Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
Xie Z et al.·Bioengineered
2021
Association of PRKCA expression and polymorphisms with layer duck eggshell quality.
Tan GH et al.·Br Poult Sci
2021
Identification of Novel Anthracycline Resistance Genes and Their Inhibitors
Kadioglu O et al.·Pharmaceuticals (Basel)
2021
Study on the expression of lncRNA PRKCA-AS1 in oral squamous cell carcinoma.
Wang D et al.·Transl Cancer Res
2024
Papillary Glioneuronal Tumor With a Novel GPR37L1-PRKCA Fusion.
Ahn JS et al.·J Neuropathol Exp Neurol
2021
Preclinical In Silico Evidence Indicates the Pharmacological Targets and Mechanisms of Mogroside V in Patients With Ovarian Cancer and Coronavirus Disease 2019
Li Y et al.·Front Endocrinol (Lausanne)
2022Cohort
SLC44A1::PRKCA fusion-positive glioneuronal tumor without histological and epigenetic features of papillary glioneuronal tumor.
Huynh V et al.·J Neuropathol Exp Neurol
2025
Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of asparagus against polycystic ovary syndrome
Xing J et al.·J Ovarian Res
2023Functional
tsRNA-04002 alleviates intervertebral disk degeneration by targeting PRKCA to inhibit apoptosis of nucleus pulposus cells
Pan J et al.·J Orthop Surg Res
2023
Top 9 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients