PDE3A
Chr 12ADphosphodiesterase 3A
Also known as: CGI-PDE, CGI-PDE A, CGI-PDE-A, HTNB
The protein is a cyclic nucleotide phosphodiesterase that hydrolyzes cAMP and cGMP to regulate intracellular signaling, mediating platelet aggregation and controlling vascular smooth muscle contraction and relaxation. Mutations cause hypertension and brachydactyly syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.515), suggesting intolerance to protein-disrupting mutations.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PDE3A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools