ALDH3A2

Chr 17AR

aldehyde dehydrogenase 3 family member A2

Also known as: ALDH10, FALDH, SLS

NCBI Gene: 224 ENSG00000072210 UniProt: P51648 OMIM: 609523

The protein catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids, functioning in aldehyde detoxification from alcohol metabolism and lipid peroxidation. Mutations cause Sjögren-Larsson syndrome through an autosomal recessive inheritance pattern. The pathogenic mechanism involves loss of function, leading to toxic aldehyde accumulation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.821 OMIM phenotype

Clinical Summary— ALDH3A2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

194 unique Pathogenic / Likely Pathogenic· 169 VUS of 725 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.21

OE 0.51 (0.33–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.68Z-score

OE missense 0.88 (0.80–0.98)

245 obs / 277.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.33–0.82)

0≤0.351.4

Missense OE?0.88 (0.80–0.98)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 12 / 23.6Missense obs/exp: 245 / 277.0Syn Z: 1.53

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALDH3A2-related Sjogren-Larsson syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.79top 25%

GOF

0.75top 25%

LOF

0.2092th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

725 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic80

Likely Pathogenic114

VUS169

Likely Benign293

Benign32

Conflicting28

Pathogenic

114

Likely Pathogenic

169

VUS

293

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	58	9	13	0	80
Likely Pathogenic	80	29	4	1	114
VUS	5	120	39	5	169
Likely Benign	2	10	114	167	293
Benign	1	0	30	1	32
Conflicting	—				28
Total	146	168	200	174	716

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

View in ClinVar →

101 pathogenic / likely-pathogenic (of 122) ClinVar copy-number / structural variants overlap ALDH3A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →