ALDH5A1

Chr 6AR

aldehyde dehydrogenase 5 family member A1

Also known as: SSADH, SSDH

This mitochondrial NAD(+)-dependent enzyme catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Mutations cause succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyricaciduria), a rare autosomal recessive inborn error of GABA metabolism that leads to accumulation of GHB in physiologic fluids. The gene shows very low constraint against loss-of-function variants (pLI near zero), which is consistent with its autosomal recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.941 OMIM phenotype
Clinical SummaryALDH5A1
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Gene-Disease Validity (ClinGen)
succinic semialdehyde dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
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GeneReview available — ALDH5A1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.79
OE 0.60 (0.400.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.73Z-score
OE missense 0.88 (0.790.97)
254 obs / 289.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.400.94)
00.351.4
Missense OE0.88 (0.790.97)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 14 / 23.4Missense obs/exp: 254 / 289.1Syn Z: 0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveALDH5A1-related succinate semialdehyde dehydrogenase deficiencyLOFAR

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

DN
0.75top 25%
GOF
0.6444th %ile
LOF
0.3066th %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

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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