PTGS1

Chr 9

prostaglandin-endoperoxide synthase 1

Also known as: COX1, COX3, PCOX1, PES-1, PGG/HS, PGHS-1, PGHS1, PHS1

The protein functions as a dual cyclooxygenase and peroxidase enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H2, the precursor of all prostaglandins and thromboxanes, with constitutive roles in gastric cytoprotection and platelet aggregation. Based on the provided information, no specific pediatric neurogenetic diseases have been definitively associated with PTGS1 mutations, though the predicted gain-of-function mechanism and low constraint metrics suggest potential pathogenicity when mutated.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.78
Clinical SummaryPTGS1
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Gene-Disease Validity (ClinGen)
platelet-type bleeding disorder 12 · SDLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.47
OE 0.51 (0.340.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.57Z-score
OE missense 0.92 (0.841.00)
338 obs / 368.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.340.78)
00.351.4
Missense OE0.92 (0.841.00)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 15 / 29.5Missense obs/exp: 338 / 368.8Syn Z: 0.14
DN
0.6260th %ile
GOF
0.6443th %ile
LOF
0.2484th %ile

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

GOFprediction above median
DNprediction 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

PTGS1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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