ALDH3A1

Chr 17

aldehyde dehydrogenase 3 family member A1

Also known as: ALDH3, ALDHIII

The enzyme oxidizes aromatic and medium-chain aldehydes to corresponding acids and comprises about 50% of corneal epithelial soluble proteins, playing a role in protecting the cornea from UV-induced oxidative damage. Biallelic mutations cause autosomal recessive microphthalmia with coloboma and other eye abnormalities. The gene shows low constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance requiring biallelic mutations for disease.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.53
Clinical SummaryALDH3A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.53LOEUF
pLI 0.000
Z-score -0.40
OE 1.09 (0.791.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.30Z-score
OE missense 0.95 (0.861.05)
273 obs / 287.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.09 (0.791.53)
00.351.4
Missense OE0.95 (0.861.05)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 24 / 22.0Missense obs/exp: 273 / 287.1Syn Z: -0.58
DN
0.7327th %ile
GOF
0.6639th %ile
LOF
0.2874th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALDH3A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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