P4HA3

Chr 11

prolyl 4-hydroxylase subunit alpha 3

NCBI Gene: 283208 ENSG00000149380 UniProt: Q7Z4N8

This gene encodes an alpha subunit of prolyl 4-hydroxylase, which catalyzes the post-translational formation of 4-hydroxyproline in collagen sequences essential for proper procollagen folding. The gene is not constrained against loss-of-function variants and no established Mendelian diseases have been definitively linked to P4HA3 mutations in current medical literature. Clinical significance of variants in this gene remains uncertain and requires careful interpretation in the context of patient phenotype.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.80

OE 0.64 (0.45–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.53Z-score

OE missense 0.91 (0.83–1.01)

268 obs / 293.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.45–0.94)

0≤0.351.4

Missense OE?0.91 (0.83–1.01)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 19 / 29.6Missense obs/exp: 268 / 293.4Syn Z: 0.97

Background carrier burden — how many people carry a rare variant somewhere in P4HA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

825 rare PASS variants

Rare truncating (LoF)

1 in 1,900

116 rare PASS variants

Rare synonymous (reference)

1 in 330

274 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for P4HA3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 85	1 in 2,400
South Asian	~43k	1 in 73	1 in 890
Remaining (unassigned)	~30k	1 in 64	1 in 2,900
European (Finnish)	~27k	1 in 150	1 in 3,500
Admixed American	~22k	1 in 81	1 in 800
African / African American	~21k	1 in 78	1 in 880
East Asian	~20k	1 in 75	1 in 910
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 100	≈ 1 in 970

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 13 coding exons well covered in gnomAD exomes; exons 5, 10 marginal. Genomes: 12 of 13 (exon 5 below).? see exons ↓