P3H1
Chr 1ARprolyl 3-hydroxylase 1
Also known as: GROS1, LEPRE1, OI8
This gene encodes a prolyl 3-hydroxylase that catalyzes the post-translational formation of 3-hydroxyproline in collagen types IV and V, which is essential for proper collagen synthesis and assembly in the endoplasmic reticulum. Mutations cause osteogenesis imperfecta type VIII, a severe bone fragility disorder with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (LOEUF 1.226), suggesting that complete loss of function may be required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
600 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 | 46 | 0 | 5 | 0 | 51 |
Likely Pathogenic | 34 | 3 | 3 | 0 | 40 |
VUS | 3 | 135 | 13 | 4 | 155 |
Likely Benign | 0 | 10 | 137 | 185 | 332 |
Benign | 0 | 0 | 4 | 0 | 4 |
Conflicting | — | 8 | |||
| Total | 83 | 148 | 162 | 189 | 590 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
P3H1 · 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