PDE6B

Chr 4ADAR

phosphodiesterase 6B

Also known as: CSNB3, CSNBAD2, GMP-PDEbeta, PDEB, RP40, rd1

NCBI Gene: 5158 ENSG00000133256 UniProt: P35913 OMIM: 180072

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Photon absorption triggers a signaling cascade in rod photoreceptors that activates cGMP phosphodiesterase (PDE), resulting in the rapid hydrolysis of cGMP, closure of cGMP-gated cation channels, and hyperpolarization of the cell. PDE is a peripheral membrane heterotrimeric enzyme made up of alpha, beta, and gamma subunits. This gene encodes the beta subunit. Mutations in this gene result in retinitis pigmentosa and autosomal dominant congenital stationary night blindness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 1.192 OMIM phenotypes

Clinical Summary— PDE6B

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Gene-Disease Validity (ClinGen)

inherited retinal dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

188 unique Pathogenic / Likely Pathogenic· 589 VUS of 1310 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PDE6B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 0.51

OE 0.92 (0.72–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.80Z-score

OE missense 1.10 (1.02–1.18)

572 obs / 520.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.92 (0.72–1.19)

0≤0.351.4

Missense OE?1.10 (1.02–1.18)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 43 / 46.7Missense obs/exp: 572 / 520.8Syn Z: -1.42

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePDE6B-related retinitis pigmentosaLOFAR

strongPDE6B-related night blindness, congenital stationaryGOFAD

This gene — mechanism propensity

0.6161th %ile

GOF

0.74top 25%

LOF

0.3746th %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

1310 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic107

Likely Pathogenic81

VUS589

Likely Benign368

Benign56

Conflicting97

107

Pathogenic

Likely Pathogenic

589

VUS

368

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	86	11	10	0	107
Likely Pathogenic	50	25	6	0	81
VUS	8	503	60	18	589
Likely Benign	3	11	158	196	368
Benign	1	6	46	3	56
Conflicting	—				97
Total	148	556	280	217	1,298

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

148 pathogenic / likely-pathogenic (of 174) ClinVar copy-number / structural variants overlap PDE6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →