P4HA1

Chr 10

prolyl 4-hydroxylase subunit alpha 1

Also known as: P4HA

NCBI Gene: 5033ENSG00000122884UniProt: P13674

This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
62
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.34
LOEUF· LoF intol.
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.34LOEUF
pLI 0.932
Z-score 4.29
OE 0.16 (0.08–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.01Z-score
OE missense 0.67 (0.59–0.75)
195 obs / 291.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.16 (0.08–0.34)
0≤0.351.4
Missense OE?0.67 (0.59–0.75)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 5 / 30.6Missense obs/exp: 195 / 291.8Syn Z: 0.41

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

P4HA1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients