PDE6D

Chr 2

phosphodiesterase 6D

Also known as: JBTS22, PDED

NCBI Gene: 5147 ENSG00000156973 UniProt: O43924

The encoded protein promotes the release of prenylated proteins from cellular membranes and is required for normal ciliary targeting of farnesylated proteins, functioning as a GTP-specific dissociation inhibitor that modulates ARL3 activity. Mutations cause Joubert syndrome 22, a ciliopathy affecting the brain, kidneys, liver, and retina. This condition follows autosomal recessive inheritance.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the delta subunit of rod-specific photoreceptor phosphodiesterase (PDE), a key enzyme in the phototransduction cascade. A similar protein in cow functions in solubilizing membrane-bound PDE. In addition to its role in the PDE complex, the encoded protein is thought to bind to prenyl groups of proteins to target them to subcellular organelles called cilia. Mutations in this gene are associated with Joubert syndrome-22. Alternative splicing results in multiple splice variants. [provided by RefSeq, Mar 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtJoubert syndrome 22

Clinical highlights

Gene-disease validity (ClinGen)

ciliopathy · ARModerateconsider for supplementary testing

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)

—

P/LP submissions

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P/LP missense

1.02

LOEUF

LOF

Mechanism· G2P

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GeneReview available — PDE6D