PTGFR

Chr 1

prostaglandin F receptor

Also known as: FP

The PTGFR protein is a G-protein coupled receptor that binds prostaglandin F2-alpha and activates phosphatidylinositol-calcium signaling pathways, with roles in smooth muscle contraction and modulating intraocular pressure. Mutations cause autosomal recessive primary congenital glaucoma, typically presenting in infancy with elevated intraocular pressure, corneal clouding, and progressive vision loss. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.754), consistent with its autosomal recessive inheritance pattern.

Summary from RefSeq, UniProt
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0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.75
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPTGFR
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.066
Z-score 2.17
OE 0.33 (0.160.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.17Z-score
OE missense 0.76 (0.670.88)
149 obs / 194.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.160.75)
00.351.4
Missense OE0.76 (0.670.88)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 4 / 12.1Missense obs/exp: 149 / 194.9Syn Z: 0.05
DN
0.75top 25%
GOF
0.80top 10%
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

PTGFR · 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.

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Clinical Literature
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