PDE6D

Chr 2AR

phosphodiesterase 6D

Also known as: JBTS22, PDED

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Joubert syndrome 22MIM #615665
AR
0
Active trials
11
Pubs (1 yr)
41
P/LP submissions
0%
P/LP missense
1.02
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPDE6D
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 31 VUS of 112 total submissions
📖
GeneReview available — PDE6D
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.006
Z-score 1.54
OE 0.48 (0.251.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.60Z-score
OE missense 0.52 (0.410.66)
45 obs / 87.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.251.02)
00.351.4
Missense OE0.52 (0.410.66)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 5 / 10.3Missense obs/exp: 45 / 87.0Syn Z: 0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPDE6D-related Joubert syndromeLOFAR

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

DN
0.6648th %ile
GOF
0.4283th %ile
LOF
0.3356th %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

112 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic3
VUS31
Likely Benign39
36
Pathogenic
3
Likely Pathogenic
31
VUS
39
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
32
0
36
Likely Pathogenic
2
0
1
0
3
VUS
0
22
8
1
31
Likely Benign
0
2
16
21
39
Benign
0
0
0
0
0
Total6245722109

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

View in ClinVar →

Protein Context — Lollipop Plot

PDE6D · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC