ALDH5A1

Chr 6AR

aldehyde dehydrogenase 5 family member A1

ENSG00000112294UniProt: P51649

Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)

Primary Disease Associations & Inheritance

Succinic semialdehyde dehydrogenase deficiencyMIM #271980
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ALDH5A1
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Gene-Disease Validity (ClinGen)
succinic semialdehyde dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.94LOEUF
pLI 0.000
Z-score 1.79
OE 0.60 (0.40–0.94)
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.
0.73Z-score
OE missense 0.88 (0.79–0.97)
254 obs / 289.1 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.0.60 (0.40–0.94)
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 (0.79–0.97)
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.0.94
0≤1.21.6
LoF obs/exp: 14 / 23.4Missense obs/exp: 254 / 289.1Syn Z: 0.54

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ALDH5A1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALDH5A1-related succinate semialdehyde dehydrogenase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Succinic semialdehyde dehydrogenase deficiency

MIM #271980

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Bioinformatics Analysis Reveals ALDH5A1: A Novel Molecular Brake on Th17 Cell Pathogenicity in Systemic Lupus Erythematosus.
Yu H et al.·FASEB J
2026
A novel hereditary encephalopathy in four related Labrador Retrievers associated with a missense variant in the ALDH5A1 gene.
Schofield E et al.·J Vet Intern Med
2026🔓 Open Access
ALDH5A1/miR-210 axis plays a key role in reprogramming cellular metabolism and has a significant correlation with glioblastoma patient survival.
Mondal I et al.·Cancer Cell Int
2024🔓 Open Access
Downregulation of ALDH5A1 suppresses cisplatin resistance in esophageal squamous cell carcinoma by regulating ferroptosis signaling pathways.
Song K et al.·Mol Carcinog
2024
Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.
Dong H et al.·BMC Med Genomics
2024🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools