ALDH1B1

Chr 9

aldehyde dehydrogenase 1 family member B1

Also known as: ALDH5, ALDHX

NCBI Gene: 219ENSG00000137124UniProt: P30837OMIM: 100670

This aldehyde dehydrogenase catalyzes the oxidation of acetaldehyde to acetate in alcohol metabolism and is involved in detoxifying aldehydes from corticosteroid metabolism, neurotransmitters, and lipid peroxidation. Mutations cause autosomal recessive mitochondrial complex I deficiency with varied presentations including leigh syndrome, hypertrophic cardiomyopathy, and hepatopathy with onset ranging from neonatal to adult periods. The gene is highly constrained against loss-of-function variants (pLI near 1.0), indicating intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.30
Clinical Summary— ALDH1B1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 unique Pathogenic / Likely Pathogenic· 67 VUS of 157 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
1.30LOEUF
pLI 0.000
Z-score 0.78
OE 0.77 (0.47–1.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.23Z-score
OE missense 1.04 (0.95–1.13)
333 obs / 321.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.77 (0.47–1.30)
0≤0.351.4
Missense OE1.04 (0.95–1.13)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 10 / 13.0Missense obs/exp: 333 / 321.5Syn Z: 0.49
DN
0.7229th %ile
GOF
0.5955th %ile
LOF
0.2968th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

157 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic9
VUS67
Likely Benign5
Benign12
60
Pathogenic
9
Likely Pathogenic
67
VUS
5
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
1
8
0
9
VUS
0
62
5
0
67
Likely Benign
2
2
1
0
5
Benign
0
4
2
6
12
Total269766153

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

View in ClinVar →

Protein Context — Lollipop Plot

ALDH1B1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Exploring the Role and Pathophysiological Significance of Aldehyde Dehydrogenase 1B1 (ALDH1B1) in Human Lung Adenocarcinoma.
Tsochantaridis I et al.·Int J Mol Sci
2024
Human ALDH1B1 polymorphisms may affect the metabolism of acetaldehyde and all-trans retinaldehyde--in vitro studies and computational modeling.
Jackson BC et al.·Pharm Res
2015Functional
Protein Methyltransferase Inhibition Decreases Endocrine Specification Through the Upregulation of Aldh1b1 Expression.
Giannios I et al.·Stem Cells
2019
Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.
Koyanagi YN et al.·Sci Adv
2024Meta-analysis
Genomic variants and inferred biological processes in multiplex families with Tourette syndrome.
Fichna JP et al.·J Psychiatry Neurosci
2023
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients