PTGDS

Chr 9

prostaglandin D2 synthase

Also known as: L-PGDS, LPGDS, PDS, PGD2, PGDS, PGDS2

This protein catalyzes the conversion of prostaglandin H2 to prostaglandin D2, which functions as a neuromodulator and trophic factor in the central nervous system and is involved in non-rapid eye movement sleep regulation. The gene shows very low intolerance to loss-of-function variants (pLI 0.005) and has a predicted de novo mechanism of pathogenicity, but no specific disease phenotypes are provided in the available data. The protein also binds lipophilic molecules and may contribute to blood-brain barrier maintenance and CNS development.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.85
Clinical SummaryPTGDS
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
0.85LOEUF
pLI 0.005
Z-score 1.98
OE 0.43 (0.230.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.53Z-score
OE missense 0.86 (0.731.02)
101 obs / 117.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.230.85)
00.351.4
Missense OE0.86 (0.731.02)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 6 / 14.0Missense obs/exp: 101 / 117.2Syn Z: 0.36
DN
0.7229th %ile
GOF
0.6541th %ile
LOF
0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTGDS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

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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