PDE6H

Chr 12

phosphodiesterase 6H

Also known as: ACHM6, RCD3

NCBI Gene: 5149 ENSG00000139053 UniProt: Q13956

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the inhibitory (or gamma) subunit of the cone-specific cGMP phosphodiesterase, which is a tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma). It is specifically expressed in the retina, and is involved in the transmission and amplification of the visual signal. Mutations in this gene are associated with retinal cone dystrophy type 3A (RCD3A). [provided by RefSeq, Mar 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAchromatopsia 6

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.81

LOEUF

LOF

Mechanism· G2P

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GeneReview available — PDE6H