ALDH3A1

Chr 17

aldehyde dehydrogenase 3 family member A1

Also known as: ALDH3, ALDHIII

NCBI Gene: 218ENSG00000108602UniProt: P30838

Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]

160
ClinVar variants
99
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALDH3A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 51 VUS of 160 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.
1.53LOEUF
pLI 0.000
Z-score -0.40
OE 1.09 (0.79–1.53)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.30Z-score
OE missense 0.95 (0.86–1.05)
273 obs / 287.1 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.1.09 (0.79–1.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.05)
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.1.07
0≤1.21.6
LoF obs/exp: 24 / 22.0Missense obs/exp: 273 / 287.1Syn Z: -0.58

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic3
VUS51
Likely Benign5
Benign5
96
Pathogenic
3
Likely Pathogenic
51
VUS
5
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
1
2
0
3
VUS
0
37
14
0
51
Likely Benign
0
3
1
1
5
Benign
0
1
0
4
5
Total0421135160

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming.
Chen Y et al.·Cell Death Dis
2023
Lian Qiao Wen Dan Decoction attenuates gastric carcinogenesis by alleviating oxidative phosphorylation dysfunction.
Chi X et al.·Phytomedicine
2025
ALDH Enzymes and Hematological Diseases: A Scoping Review of Literature.
Foucault A et al.·Discov Med
2024Review
Corneal strain influences keratocyte proliferation and migration through upregulation of ALDH3A1 expression.
Zhang Q et al.·FASEB J
2024
Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease.
Balestrieri N et al.·Circ Res
2023
ALDH3A1 upregulation inhibits neutrophils N2 polarization and halts oral cancer growth.
He Y et al.·Oral Dis
2024
Identification of proteomic signatures associated with lung cancer and COPD.
Pastor MD et al.·J Proteomics
2013Clinical trial
Multi-omics revealed GOT1/ALDH3A1 pathway attenuated head and neck squamous cell carcinoma and increased cisplatin sensitivity through ROS induced by mitochondrial dysfunction.
Liu Z et al.·Redox Rep
2025
ALDH3A1 overexpression in OSCC inhibits inflammation via phospho-Ser727 at STAT3 in tumor-associated macrophages.
Wang B et al.·Oral Dis
2023
Exploring the mechanisms of glycolytic genes involvement in pulmonary arterial hypertension through integrative bioinformatics analysis.
Lou YX et al.·J Cell Mol Med
2024Functional
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