PDE8B

Chr 5

phosphodiesterase 8B

Also known as: ADSD, PPNAD3

NCBI Gene: 8622ENSG00000284762UniProt: O95263

The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtStriatal degeneration, autosomal dominant 1
UniProtPrimary pigmented nodular adrenocortical disease 3

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
14
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
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GeneReview available — PDE8B
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.25LOEUF
pLI 0.999
Z-score 5.31
OE 0.12 (0.06–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.00Z-score
OE missense 0.62 (0.56–0.68)
305 obs / 492.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.06–0.25)
0≤0.351.4
Missense OE?0.62 (0.56–0.68)
0≤0.61.4
Synonymous OE?1.06
0≤1.21.6
LoF obs/exp: 5 / 42.2Missense obs/exp: 305 / 492.1Syn Z: -0.69

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PDE8B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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