PDE6H

Chr 12AR

phosphodiesterase 6H

Also known as: ACHM6, RCD3

The protein functions as the inhibitory gamma subunit of cone-specific cGMP phosphodiesterase, which is essential for phototransduction and visual signal transmission in retinal cone cells. Mutations cause achromatopsia 6, a retinal cone dystrophy affecting color vision and visual acuity, with autosomal recessive inheritance. This gene shows tolerance to loss-of-function variants (pLI 0.008, LOEUF 1.81), suggesting that complete loss of both copies is required for disease manifestation.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Achromatopsia 6MIM #610024
AR
0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.81
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPDE6H
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.81LOEUF
pLI 0.008
Z-score 0.21
OE 0.88 (0.391.81)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.19Z-score
OE missense 0.92 (0.721.19)
43 obs / 46.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.88 (0.391.81)
00.351.4
Missense OE0.92 (0.721.19)
00.61.4
Synonymous OE1.24
01.21.6
LoF obs/exp: 3 / 3.4Missense obs/exp: 43 / 46.7Syn Z: -0.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPDE6H-related retinal cone dystrophyOTHERAR
strongPDE6H-related achromatopsiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.79top 25%
GOF
0.6053th %ile
LOF
0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PDE6H · 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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