P4HA2

Chr 5AD

prolyl 4-hydroxylase subunit alpha 2

NCBI Gene: 8974ENSG00000072682UniProt: O15460

Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins

Primary Disease Associations & Inheritance

Myopia 25, autosomal dominantMIM #617238
AD
144
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— P4HA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 97 VUS of 144 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.
0.66LOEUF
pLI 0.000
Z-score 3.20
OE 0.43 (0.29–0.66)
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.
0.82Z-score
OE missense 0.87 (0.79–0.96)
272 obs / 312.9 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.0.43 (0.29–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.79–0.96)
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.1.00
0≤1.21.6
LoF obs/exp: 16 / 37.0Missense obs/exp: 272 / 312.9Syn Z: -0.02

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic4
VUS97
Likely Benign22
Benign3
Conflicting1
17
Pathogenic
4
Likely Pathogenic
97
VUS
22
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
15
0
17
Likely Pathogenic
0
2
2
0
4
VUS
1
88
7
1
97
Likely Benign
1
5
4
12
22
Benign
0
0
3
0
3
Conflicting
—1
Total3963113144

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

View in ClinVar →

Protein Context — Lollipop Plot

P4HA2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

P4HA2-related myopia

strong
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myopia 25, autosomal dominant

MIM #617238

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell and spatial transcriptomics reveal P4HA2-mediated radiotherapy resistance mechanisms in breast cancer.
Li H et al.·Theranostics
2026Functional
Familial Whole Exome Sequencing Study of 30 Families With Early-Onset High Myopia.
Yang E et al.·Invest Ophthalmol Vis Sci
2023
YTHDF3-induced degradation of P4HA2 mRNA inhibits glycolysis in papillary thyroid cancer through Hippo signaling pathway.
Ding Y et al.·Int J Biol Macromol
2025
Identification of thyroid cancer biomarkers using WGCNA and machine learning.
Hu G et al.·Eur J Med Res
2025
Autosomal-dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation.
Napolitano F et al.·Clin Genet
2018
CEBPB upregulates P4HA2 to promote the malignant biological behavior in IDH1 wildtype glioma.
Wang S et al.·FASEB J
2023
Collagen Prolyl Hydroxylases Are Bifunctional Growth Regulators in Melanoma.
Atkinson A et al.·J Invest Dermatol
2019Review
P4HA2 knockdown prevents the progression of intracranial aneurysm by inducing prolyl hydroxylation of YAP1.
Li L et al.·Neurosurg Rev
2024
High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis.
Lu XH et al.·Clinics (Sao Paulo)
2022
P4HA2 promotes the progression of thyroid cancer by regulating PFKP-mediated glycolysis.
Sun J et al.·J Physiol Biochem
2025
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