ABAT

Chr 16AR

4-aminobutyrate aminotransferase

Also known as: GABA-AT, GABAT, NPD009

NCBI Gene: 18ENSG00000183044UniProt: P80404

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]

Primary Disease Associations & Inheritance

GABA-transaminase deficiencyMIM #613163
AR
576
ClinVar variants
55
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— ABAT
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 267 VUS of 576 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.57LOEUF
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?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.
0.57Z-score
OE missense 0.91 (0.82–1.00)
266 obs / 293.6 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.0.32 (0.20–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.00)
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.1.08
0≤1.21.6
LoF obs/exp: 9 / 27.7Missense obs/exp: 266 / 293.6Syn Z: -0.64

ClinVar Variant Classifications

576 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic22
VUS267
Likely Benign219
Benign14
Conflicting21
33
Pathogenic
22
Likely Pathogenic
267
VUS
219
Likely Benign
14
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
4
24
0
33
Likely Pathogenic
11
2
9
0
22
VUS
4
161
100
2
267
Likely Benign
1
7
109
102
219
Benign
0
0
14
0
14
Conflicting
—21
Total21174256104576

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

View in ClinVar →

Protein Context — Lollipop Plot

ABAT · protein map & ClinVar variants

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

Gene2Phenotype Curations

ABAT-related GABA-transaminase 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

GABA-transaminase deficiency

MIM #613163

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ABAT
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial DNA maintenance defects.
El-Hattab AW et al.·Biochim Biophys Acta Mol Basis Dis
2017Review
Genetic variations in GABA metabolism and epilepsy.
Feng Y et al.·Seizure
2022Review
ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma.
Lu J et al.·J Transl Med
2020
Loss of ABAT-Mediated GABAergic System Promotes Basal-Like Breast Cancer Progression by Activating Ca(2+)-NFAT1 Axis.
Chen X et al.·Theranostics
2019
A crucial exosome-related gene pair (AAMP and ABAT) is associated with inflammatory cells in intervertebral disc degeneration.
Ren H et al.·Front Immunol
2023
Epigenetic dysregulation of articular cartilage during progression of hip femoroacetabular impingement disease.
Kamenaga T et al.·J Orthop Res
2023
Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma.
Liu Y et al.·Rev Invest Clin
2023
Metabolically active brown adipose tissue in PPGL: an observational cohort study.
Oštarijaš E et al.·Endocr Relat Cancer
2025Cohort
Polymorphisms of ABAT, SCN2A and ALDH5A1 may affect valproic acid responses in the treatment of epilepsy in Chinese.
Li X et al.·Pharmacogenomics
2016
GABAergic signaling contributes to tumor cell invasion and poor overall survival in colorectal cancer.
Strelez C et al.·Oncogene
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools