ALDH3A2

Chr 17AR

aldehyde dehydrogenase 3 family member A2

Also known as: ALDH10, FALDH, SLS

NCBI Gene: 224ENSG00000072210UniProt: P51648

Aldehyde dehydrogenase isozymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This gene product catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. Mutations in the gene cause Sjogren-Larsson syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Sjogren-Larsson syndromeMIM #270200
AR
UniProtSjoegren-Larsson syndrome
538
ClinVar variants
222
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ALDH3A2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
222 Pathogenic / Likely Pathogenic· 74 VUS of 538 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.82LOEUF
pLI 0.000
Z-score 2.21
OE 0.51 (0.33–0.82)
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.
0.68Z-score
OE missense 0.88 (0.80–0.98)
245 obs / 277.0 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.0.51 (0.33–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.98)
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.0.81
0≤1.21.6
LoF obs/exp: 12 / 23.6Missense obs/exp: 245 / 277.0Syn Z: 1.53

ClinVar Variant Classifications

538 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic160
Likely Pathogenic62
VUS74
Likely Benign185
Benign32
Conflicting25
160
Pathogenic
62
Likely Pathogenic
74
VUS
185
Likely Benign
32
Benign
25
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
38
11
111
0
160
Likely Pathogenic
29
13
20
0
62
VUS
3
29
42
0
74
Likely Benign
1
6
77
101
185
Benign
0
0
30
2
32
Conflicting
—25
Total7159280103538

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

View in ClinVar →

Protein Context — Lollipop Plot

ALDH3A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALDH3A2-related Sjogren-Larsson syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Sjogren-Larsson syndrome

MIM #270200

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sjogren-Larsson syndrome associated hypermelanosis.
Xu YC et al.·J Cosmet Dermatol
2020Review
ALDH3A2 targets arachidonic acid to promote cell metastasis in TNBC via AMPK/m-TOR signaling pathway.
Wang D et al.·Breast Cancer Res
2025
ALDH Enzymes and Hematological Diseases: A Scoping Review of Literature.
Foucault A et al.·Discov Med
2024Review
ALDH3A2 negatively orchestrates gastric cancer progression through a synergistic induction of ferroptosis and ferroptosis-driven macrophage reprogramming.
Ren Y et al.·Cell Death Dis
2025
Clinical, biochemical, and genetic aspects of Sjögren-Larsson syndrome.
Cho KH et al.·Clin Genet
2018Review
Novel ALDH3A2 mutations in structural and functional domains of FALDH causing diverse clinical phenotypes in Sjögren-Larsson syndrome patients.
Rajeshwari M et al.·Hum Mutat
2021Cohort
Genetic assessment of ten Egyptian patients with Sjögren-Larsson syndrome: expanding the clinical spectrum and reporting a novel ALDH3A2 mutation.
Amr K et al.·Arch Dermatol Res
2019Cohort
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.
Chen W et al.·Cardiovasc Diabetol
2024Review
Phenotypic and mutational spectrum of thirty-five patients with Sjögren-Larsson syndrome: identification of eleven novel ALDH3A2 mutations and founder effects.
Abdel-Hamid MS et al.·J Hum Genet
2019Cohort
Genotype and phenotype variability in Sjögren-Larsson syndrome.
Weustenfeld M et al.·Hum Mutat
2019
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
Sjogren-Larsson Syndrome

ADX-629 Therapy for Sjogren-Larsson Syndrome

ACTIVE NOT RECRUITING
NCT05443685Phase PHASE1, PHASE2University of NebraskaStarted 2023-01-02
ADX-629

External Resources

Links to major genomics databases and tools