ABAT

Chr 16AR

4-aminobutyrate aminotransferase

Also known as: GABA-AT, GABAT, NPD009

NCBI Gene: 18 ENSG00000183044 UniProt: P80404 OMIM: 137150

4-aminobutyrate aminotransferase catalyzes the breakdown of GABA, the brain's primary inhibitory neurotransmitter, into succinate semialdehyde. Mutations cause GABA-transaminase deficiency, an autosomal recessive disorder characterized by early-onset psychomotor retardation, hypotonia, hyperreflexia, lethargy, and refractory seizures with EEG abnormalities. The gene shows moderate intolerance to loss-of-function variants (LOEUF 0.567).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. GABA is estimated to be present in nearly one-third of human synapses. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

GABA-transaminase deficiencyMIM #613163

Clinical highlights

Gene-disease validity (ClinGen)

genetic developmental and epileptic encephalopathy · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ABAT