ABAT

Chr 16

4-aminobutyrate aminotransferase

Also known as: GABA-AT, GABAT, NPD009

NCBI Gene: 18 ENSG00000183044 UniProt: P80404

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 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 ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.57

Clinical Summary— ABAT

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Gene-Disease Validity (ClinGen)

genetic developmental and epileptic encephalopathy · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

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ClinVar Variants

48 unique Pathogenic / Likely Pathogenic· 337 VUS of 835 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ABAT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.006

Z-score 3.29

OE 0.32 (0.20–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.57Z-score

OE missense 0.91 (0.82–1.00)

266 obs / 293.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.20–0.57)

0≤0.351.4

Missense OE?0.91 (0.82–1.00)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 9 / 27.7Missense obs/exp: 266 / 293.6Syn Z: -0.64

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveABAT-related GABA-transaminase deficiencyLOFAR

This gene — mechanism propensity

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

0.75top 25%

GOF

0.5759th %ile

LOF

0.3065th %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

835 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic27

VUS337

Likely Benign330

Benign64

Conflicting33

Pathogenic

Likely Pathogenic

337

VUS

330

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	6	6	0	21
Likely Pathogenic	20	4	3	0	27
VUS	6	232	96	3	337
Likely Benign	4	9	169	148	330
Benign	0	2	56	6	64
Conflicting	—				33
Total	39	253	330	157	812

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 85) ClinVar copy-number / structural variants overlap ABAT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →