P4HA3

Chr 11

prolyl 4-hydroxylase subunit alpha 3

NCBI Gene: 283208ENSG00000149380UniProt: Q7Z4N8

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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

93
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— P4HA3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 81 VUS of 93 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.80
OE 0.64 (0.45–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.53Z-score
OE missense 0.91 (0.83–1.01)
268 obs / 293.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.45–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.83–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 19 / 29.6Missense obs/exp: 268 / 293.4Syn Z: 0.97

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS81
Likely Benign4
8
Pathogenic
81
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
78
3
0
81
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total08111193

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

P4HA3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
P4HA3 depletion induces ferroptosis and inhibits colorectal cancer growth by stabilizing ACSL4 mRNA.
Xu W et al.·Biochem Pharmacol
2025
Collagen Prolyl Hydroxylases Are Bifunctional Growth Regulators in Melanoma.
Atkinson A et al.·J Invest Dermatol
2019Review
CT-Based Radiogenomics of P4HA3 Expression in Clear Cell Renal Cell Carcinoma.
Greco F et al.·Acad Radiol
2024
COL6A6 interacted with P4HA3 to suppress the growth and metastasis of pituitary adenoma via blocking PI3K-Akt pathway.
Long R et al.·Aging (Albany NY)
2019
Prognostic and diagnostic roles of prolyl 4-hydroxylase subunit α members in breast cancer.
Li M et al.·Biomark Med
2021
Construction of iron metabolism-related prognostic features of gastric cancer based on RNA sequencing and TCGA database.
Liu X et al.·BMC Cancer
2023
Protrec2: tissue-specific network-based missing protein recovery method.
Kong W et al.·Brief Bioinform
2025
A Prognostic Model Based on Six Metabolism-Related Genes in Colorectal Cancer.
Sun YL et al.·Biomed Res Int
2020Functional
Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.
van den Akker GG et al.·PLoS One
2016
DKK3 expression is correlated with poorer prognosis in head and neck squamous cell carcinoma: A bioinformatics study based on the TCGA database.
Katase N et al.·J Oral Biosci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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