PDE9A

Chr 21

phosphodiesterase 9A

Also known as: HSPDE9A2

The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

0
Active trials
12
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.48
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPDE9A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.005
Z-score 4.11
OE 0.30 (0.190.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.09Z-score
OE missense 0.84 (0.760.92)
307 obs / 365.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.190.48)
00.351.4
Missense OE0.84 (0.760.92)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 12 / 40.1Missense obs/exp: 307 / 365.5Syn Z: 0.48
DN
0.6551th %ile
GOF
0.7126th %ile
LOF
0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PDE9A · protein map & ClinVar variants

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

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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