PTGR1
Chr 9prostaglandin reductase 1
Also known as: DIG-1, LTB4DH, PGR1, ZADH3
The encoded enzyme catalyzes the NADP+-dependent reduction of pro- and anti-inflammatory eicosanoids including prostaglandins, leukotrienes, and lipoxins, and also reduces cytotoxic aldehydes like 4-hydroxy-2-nonenal. Biallelic mutations in PTGR1 cause infantile-onset neurodegeneration with brain atrophy, characterized by severe developmental delay, seizures, and progressive brain volume loss. This gene follows autosomal recessive inheritance and is not highly constrained against loss-of-function variation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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.
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
113 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 28 | 0 | 28 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 43 | 4 | 0 | 47 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 0 | 47 | 38 | 0 | 85 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PTGR1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools