PDE6B
Chr 4ADARphosphodiesterase 6B
Also known as: CSNB3, CSNBAD2, GMP-PDEbeta, PDEB, RP40, rd1
PDE6B encodes the beta subunit of rod-specific cGMP phosphodiesterase, which catalyzes the hydrolysis of cGMP in the visual signal transduction cascade of rod photoreceptors. Mutations cause retinitis pigmentosa-40 and autosomal dominant congenital stationary night blindness, with inheritance patterns including both autosomal dominant and autosomal recessive forms. The gene shows tolerance to loss-of-function variants (LOEUF 1.187), indicating that different mutation types may lead to distinct clinical phenotypes.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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.
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
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 18 | 1 | 33 | 0 | 52 |
Likely Pathogenic | 13 | 3 | 6 | 0 | 22 |
VUS | 4 | 209 | 22 | 9 | 244 |
Likely Benign | 0 | 5 | 77 | 84 | 166 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 3 | |||
| Total | 35 | 218 | 139 | 93 | 488 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PDE6B · 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
Natural History Study in Patients with PDE6A-, PDE6B- and RHO-linked Retinitis Pigmentosa
RECRUITINGPromising ROd-cone DYstrophy Gene therapY
RECRUITINGProspective Natural History Study of Retinitis Pigmentosa
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools