ALDH5A1

Chr 6AR

aldehyde dehydrogenase 5 family member A1

Also known as: SSADH, SSDH

NCBI Gene: 7915 ENSG00000112294 UniProt: P51649 OMIM: 610045

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Succinic semialdehyde dehydrogenase deficiencyMIM #271980

Clinical highlights

Gene-disease validity (ClinGen)

succinic semialdehyde dehydrogenase deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ALDH5A1