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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PRKACG
protein kinase cAMP-activated catalytic subunit gamma
Chromosome 9 · 9q21.11
NCBI Gene: 5568Ensembl: ENSG00000165059.8HGNC: HGNC:9382UniProt: P22612
60PubMed Papers
21Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
CLINICAL
Early PipelineOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
potassium channel inhibitor activityprotein bindingprotein kinase A regulatory subunit bindingcAMP-dependent protein kinase activityplatelet-type bleeding disorder 19Rare hemorrhagic disorder due to a constitutional platelet anomalynephrolithiasisneurodegenerative disease
✦AI Summary

PRKACG encodes the γ-catalytic subunit of cAMP-dependent protein kinase (PKA), a serine/threonine kinase expressed primarily in testis 1. As a PKA catalytic subunit, PRKACG phosphorylates numerous cytoplasmic and nuclear substrates in response to cAMP signaling 2. The protein is localized to chromosome 9 1. PRKACG plays a critical role in platelet biogenesis and function. Loss-of-function mutations impair proplatelet formation in megakaryocytes and reduce filamin A levels, leading to severe macrothrombocytopenia with giant platelets and bleeding tendency 3. A missense mutation (p.74Ile>Met) was identified as causative for inherited macrothrombocytopenia with thrombocytopathy, where platelet activation and cytoskeleton reorganization were markedly impaired 3. Overexpression of wild-type PRKACG rescued defective proplatelet formation in patient megakaryocytes, establishing PRKACG as central to platelet biogenesis 3. Clinically, PRKACG mutations constitute a newly recognized genetic cause of inherited platelet disorders 45. PRKACG is designated as the causative gene for Bleeding disorder, platelet-type, 19 6. Additionally, PRKACG expression associates with HDL metabolism in coronary artery disease patients 7, and genetic variants influence vitamin D status 8, suggesting broader metabolic functions beyond platelet biology.

Sources cited
1
PRKACG chromosomal localization to 9q13 and testis-specific expression
PMID: 1339328
2
PRKACG mutations cause macrothrombocytopenia through defects in proplatelet formation and filamin A expression
PMID: 25061177
3
PRKACG deficiency identified as cause of inherited platelet function disorder
PMID: 26149024
4
PRKACG mutations in families with severe macrothrombocytopenia discovered via next-generation sequencing
PMID: 26164464
5
PRKACG belongs to PKA catalytic subunit family with conserved kinase function
PMID: 23593352
6
PRKACG designated as disease gene for inherited macrothrombocytopenia
PMID: 25323684
7
PRKACG expression associates with HDL metabolism in coronary artery disease
PMID: 37623250
8
PRKACG variants associated with vitamin D serum concentrations
PMID: 25396269
Disease Associationsⓘ21
platelet-type bleeding disorder 19Open Targets
0.52Moderate
Rare hemorrhagic disorder due to a constitutional platelet anomalyOpen Targets
0.46Moderate
nephrolithiasisOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.24Weak
cancerOpen Targets
0.05Suggestive
migraine disorderOpen Targets
0.04Suggestive
nephrotic syndromeOpen Targets
0.03Suggestive
familial hemolytic anemiaOpen Targets
0.03Suggestive
cardiomyopathyOpen Targets
0.03Suggestive
cellulitisOpen Targets
0.03Suggestive
Abruptio PlacentaeOpen Targets
0.03Suggestive
abscessOpen Targets
0.03Suggestive
HeadacheOpen Targets
0.03Suggestive
atrioventricular blockOpen Targets
0.02Suggestive
headache disorderOpen Targets
0.02Suggestive
PainOpen Targets
0.02Suggestive
intelligenceOpen Targets
0.02Suggestive
dry eye syndromeOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
MacrothrombocytopeniaOpen Targets
0.01Suggestive
Bleeding disorder, platelet-type, 19UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
GSK-690693Phase I
Protein kinase C (PKC) inhibitor
Related Genes
AKAP9Protein interaction100%SUFUProtein interaction100%TRPV1Protein interaction100%PKIAProtein interaction100%AKAP4Protein interaction100%AKAP7Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
0%
Brain
0%
Heart
0%
Lung
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
PRKACGAKAP9SUFUTRPV1PKIAAKAP4AKAP7
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P22612
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.26LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.65–1.26]
RankingsWhere PRKACG stands among ~20K protein-coding genes
  • #7,699of 20,598
    Most Researched60
  • #13,284of 17,882
    Most Constrained (LOEUF)1.26
Genes detectedPRKACG
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Localization of the catalytic subunit C gamma of the cAMP-dependent protein kinase gene (PRKACG) to human chromosome region 9q13.
PMID: 1339328
Cytogenet Cell Genet · 1992
1.00
2
A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene.
PMID: 25061177
Blood · 2014
0.90
3
Inherited disorders of platelet function: selected updates.
PMID: 26149024
J Thromb Haemost · 2015
0.80
4
Update on the inherited platelet disorders.
PMID: 26164464
Curr Opin Hematol · 2015
0.70
5
Evolutionary paths of the cAMP-dependent protein kinase (PKA) catalytic subunits.
PMID: 23593352
PLoS One · 2013
0.60