ABAT

Summary

ABAT (4-aminobutyrate aminotransferase, HGNC:23) is a protein-coding gene on chromosome 16p13.2, encoding 4-aminobutyrate aminotransferase, mitochondrial (P80404). Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively.

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.

Source: NCBI Gene 18 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GABA aminotransaminase deficiency (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 898 total — 30 pathogenic, 23 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 31 tissues, sQTL in 12 (q < 0.05)
• Phenotypes (HPO): 34
• Drug target: yes — 1 curated mechanism-of-action drug
• Approved drugs (ChEMBL mechanism of action): 1 — Vigabatrin
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.87 (unconstrained)
• MANE Select transcript: NM_020686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23
Approved symbol	ABAT
Name	4-aminobutyrate aminotransferase
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Aliases	GABAT, GABA-T
Ensembl gene	ENSG00000183044
Ensembl biotype	protein_coding
OMIM	137150
Entrez	18

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000268251

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 3, TSL 4: 3, TSL 5: 3

ENST00000268251, ENST00000396600, ENST00000425191, ENST00000561870, ENST00000562115, ENST00000563215, ENST00000563992, ENST00000564453, ENST00000564714, ENST00000565016, ENST00000565671, ENST00000566590, ENST00000567812, ENST00000568847, ENST00000569156, ENST00000569695, ENST00000909342, ENST00000909343, ENST00000909344, ENST00000909345, ENST00000909346, ENST00000973466, ENST00001116842, ENST00001132837

RefSeq mRNA: 20 — MANE Select: NM_020686 NM_000663, NM_001127448, NM_001386600, NM_001386601, NM_001386602, NM_001386603, NM_001386604, NM_001386605, NM_001386606, NM_001386607, NM_001386608, NM_001386609, NM_001386610, NM_001386611, NM_001386612, NM_001386613, NM_001386614, NM_001386615, NM_001386616, NM_020686

CCDS: CCDS10534, CCDS92104

Canonical transcript exons

ENST00000268251 — 16 exons

Exon	Start	End
ENSE00000861767	8746001	8746098
ENSE00002581122	8674617	8674711
ENSE00003461231	8774890	8775057
ENSE00003472248	8764069	8764149
ENSE00003474659	8772780	8772917
ENSE00003481806	8766208	8766270
ENSE00003498841	8735699	8735809
ENSE00003511473	8779479	8779590
ENSE00003516022	8776344	8776490
ENSE00003520608	8748108	8748137
ENSE00003601280	8757757	8757806
ENSE00003613650	8768193	8768256
ENSE00003643965	8768825	8768973
ENSE00003658474	8764738	8764830
ENSE00003689474	8750422	8750539
ENSE00003850950	8781309	8784570

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1067 / max 1193.6546, expressed in 1302 samples.

Highest expression (Bgee): Brodmann (1909) area 23, endothelial cell, middle temporal gyrus, dorsal motor nucleus of vagus nerve, inferior olivary complex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ABAT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	1.5e-57	+0.43	16:8678720:T:C
Brain Cerebellar Hemisphere	sqtl	7.1e-41	+1.98	16:8773769:G:A
Testis	eqtl	3.6e-40	+0.67	16:8717918:A:G
Brain Cerebellum	sqtl	4.7e-40	+1.99	16:8773769:G:A
Whole Blood	eqtl	1.2e-27	-0.24	16:8729991:A:G
Brain Nucleus accumbens basal ganglia	sqtl	1.7e-25	+1.74	16:8774523:T:C
Brain Caudate basal ganglia	sqtl	4.1e-19	+1.57	16:8774523:T:C
Brain Hypothalamus	sqtl	9.1e-18	+1.68	16:8773769:G:A
Pituitary	sqtl	9.3e-16	+0.72	16:8715088:A:G
Brain Cortex	sqtl	4.1e-13	+1.40	16:8773769:G:A
Muscle Skeletal	eqtl	6.7e-13	-0.45	16:8667835:G:A
Brain Frontal Cortex BA9	sqtl	2.0e-10	+0.62	16:8715088:A:G
Spleen	eqtl	3.7e-09	-0.49	16:8730686:G:C
Nerve Tibial	eqtl	9.1e-09	-0.15	16:8671243:C:T
Cells Cultured fibroblasts	eqtl	4.8e-08	-0.27	16:8678756:G:A
Thyroid	eqtl	1.9e-07	-0.21	16:8670461:C:T
Brain Anterior cingulate cortex BA24	sqtl	2.4e-07	+0.65	16:8715088:A:G
Esophagus Muscularis	eqtl	3.0e-07	+0.16	16:8658164:T:C
Esophagus Gastroesophageal Junction	eqtl	5.1e-07	+0.19	16:8659519:A:G
Brain Spinal cord cervical c-1	eqtl	2.9e-06	-0.32	16:8680333:T:A

FANTOM5 promoters

showing 10 of 16 alternative TSS:

Promoter ID	TPM avg	Samples expressed
152650	11.3362	1189
152658	2.2692	141
152651	1.5316	510
152662	1.1592	184
152653	1.0806	164
152649	0.6593	280
152665	0.5953	235
152659	0.3356	87
152654	0.3139	140
152652	0.2570	75

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.84	gold quality
endothelial cell	CL:0000115	99.80	gold quality
middle temporal gyrus	UBERON:0002771	99.78	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.72	gold quality
inferior olivary complex	UBERON:0002127	99.52	gold quality
entorhinal cortex	UBERON:0002728	99.51	gold quality
postcentral gyrus	UBERON:0002581	99.44	gold quality
lateral globus pallidus	UBERON:0002476	99.42	gold quality
orbitofrontal cortex	UBERON:0004167	99.38	gold quality
parietal lobe	UBERON:0001872	99.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.34	gold quality
superior vestibular nucleus	UBERON:0007227	99.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.29	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.27	gold quality
substantia nigra pars compacta	UBERON:0001965	99.26	gold quality
superior frontal gyrus	UBERON:0002661	99.18	gold quality
CA1 field of hippocampus	UBERON:0003881	99.15	gold quality
medulla oblongata	UBERON:0001896	99.13	gold quality
ventral tegmental area	UBERON:0002691	99.08	gold quality
choroid plexus epithelium	UBERON:0003911	99.00	gold quality
nephron tubule	UBERON:0001231	98.90	gold quality
occipital lobe	UBERON:0002021	98.77	gold quality
primary visual cortex	UBERON:0002436	98.70	gold quality
adult organism	UBERON:0007023	98.67	gold quality
liver	UBERON:0002107	98.52	gold quality
jejunal mucosa	UBERON:0000399	98.37	gold quality
right lobe of liver	UBERON:0001114	98.21	gold quality
nucleus accumbens	UBERON:0001882	98.21	gold quality
pons	UBERON:0000988	98.17	gold quality
inferior vagus X ganglion	UBERON:0005363	98.15	gold quality
temporal lobe	UBERON:0001871	98.14	gold quality
subthalamic nucleus	UBERON:0001906	98.13	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.10	gold quality
ventricular zone	UBERON:0003053	97.93	gold quality
hypothalamus	UBERON:0001898	97.92	gold quality
caudate nucleus	UBERON:0001873	97.85	gold quality
midbrain	UBERON:0001891	97.75	gold quality
kidney epithelium	UBERON:0004819	97.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.66	gold quality
telencephalon	UBERON:0001893	97.65	gold quality
substantia nigra	UBERON:0002038	97.65	gold quality
cerebral cortex	UBERON:0000956	97.60	gold quality
globus pallidus	UBERON:0001875	97.54	gold quality
forebrain	UBERON:0001890	97.48	gold quality
putamen	UBERON:0001874	97.41	gold quality
frontal cortex	UBERON:0001870	97.40	gold quality
neocortex	UBERON:0001950	97.38	gold quality
prefrontal cortex	UBERON:0000451	97.35	gold quality
cingulate cortex	UBERON:0003027	97.33	gold quality
brain	UBERON:0000955	97.31	gold quality
amygdala	UBERON:0001876	97.31	gold quality
anterior cingulate cortex	UBERON:0009835	97.27	gold quality
central nervous system	UBERON:0001017	97.23	gold quality
Ammon’s horn	UBERON:0001954	97.23	gold quality
right frontal lobe	UBERON:0002810	97.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.12	gold quality
medial globus pallidus	UBERON:0002477	97.11	gold quality
cerebellar vermis	UBERON:0004720	96.49	gold quality
renal glomerulus	UBERON:0000074	96.38	gold quality
duodenum	UBERON:0002114	96.11	gold quality
cranial nerve II	UBERON:0000941	96.07	gold quality
adrenal tissue	UBERON:0018303	96.06	gold quality
renal medulla	UBERON:0000362	95.91	gold quality
cerebellum	UBERON:0002037	95.88	gold quality
ganglionic eminence	UBERON:0004023	95.73	gold quality
cerebellar cortex	UBERON:0002129	95.61	gold quality
cerebellar hemisphere	UBERON:0002245	95.58	gold quality
metanephric glomerulus	UBERON:0004736	95.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.40	gold quality
pituitary gland	UBERON:0000007	95.22	gold quality
bronchial epithelial cell	CL:0002328	94.92	gold quality
spinal cord	UBERON:0002240	94.81	gold quality
adenohypophysis	UBERON:0002196	94.60	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.49	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.27	gold quality
frontal pole	UBERON:0002795	93.48	gold quality
caput epididymis	UBERON:0004358	93.48	gold quality
corpus callosum	UBERON:0002336	93.38	gold quality
kidney	UBERON:0002113	93.33	gold quality
adult mammalian kidney	UBERON:0000082	93.22	gold quality
body of pancreas	UBERON:0001150	92.86	gold quality
epithelium of bronchus	UBERON:0002031	92.81	gold quality
esophagus squamous epithelium	UBERON:0006920	92.78	gold quality
paraflocculus	UBERON:0005351	92.45	gold quality
middle frontal gyrus	UBERON:0002702	92.43	gold quality
bronchus	UBERON:0002185	92.40	gold quality
cortical plate	UBERON:0005343	92.29	gold quality
germinal epithelium of ovary	UBERON:0001304	91.63	gold quality
pancreas	UBERON:0001264	91.31	gold quality
epithelium of esophagus	UBERON:0001976	91.26	gold quality
metanephros	UBERON:0000081	90.92	gold quality
olfactory bulb	UBERON:0002264	90.74	gold quality
embryo	UBERON:0000922	90.66	gold quality
epithelium of nasopharynx	UBERON:0001951	90.57	gold quality
tibia	UBERON:0000979	90.36	gold quality
secondary oocyte	CL:0000655	90.16	gold quality
epithelial cell of pancreas	CL:0000083	90.15	gold quality
trigeminal ganglion	UBERON:0001675	90.10	gold quality
cortex of kidney	UBERON:0001225	90.02	gold quality
left ventricle myocardium	UBERON:0006566	90.00	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-110499	yes	43.84
E-MTAB-7303	no	314.94
E-GEOD-99795	no	29.61
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	323.2	high
Caudate putamen	tissue	281.7
Locus coeruleus	tissue	262.2
Basal ganglia	tissue	194.8	high
Nucleus accumbens	tissue	187.7
Putamen	tissue	184.2
Postcentral gyrus	tissue	179.8
Ventral forebrain	tissue	179.4
Septum	tissue	172.3
Thalamus	tissue	160.8
Hypothalamus	tissue	160.7
Amygdala	tissue	145.0
Hippocampal formation	tissue	143.2
Frontal cortex	tissue	142.3
Pons	tissue	140.2
Cerebral cortex	tissue	137.8	high
Motor cortex	tissue	137.8
Prefrontal cortex	tissue	133.5
Periaqueductal gray	tissue	132.1
Substantia nigra	tissue	131.5
Pancreas	tissue	130.4	medium
Insular cortex	tissue	127.7
Somatosensory cortex	tissue	125.0
Kidney	tissue	124.5	high
Midbrain	tissue	123.7
Temporal cortex	tissue	120.9
Entorhinal cortex	tissue	120.6
Medulla oblongata	tissue	119.4
Superior colliculi	tissue	117.3
Choroid plexus	tissue	116.5
Retrosplenial and cingulate cortex	tissue	115.5
Retrosplenial cortex	tissue	114.6
Hippocampus	tissue	114.4	high
Occipital cortex	tissue	108.8
Olfactory bulb	tissue	103.7
Spinal cord	tissue	83.7
Cerebellum	tissue	69.1	high
Pituitary gland	tissue	53.0
Corpus callosum	tissue	51.6
Duodenum	tissue	41.1	medium
Retina	tissue	27.5
Thyroid gland	tissue	27.5	medium
Adrenal gland	tissue	26.2	medium
Prostate	tissue	20.4	medium
Small intestine	tissue	18.9	medium
Heart muscle	tissue	13.2	not detected
Testis	tissue	12.5	high
Urinary bladder	tissue	9.3	low
Epididymis	tissue	9.1	low
Ovary	tissue	7.7	not detected
Parathyroid gland	tissue	7.7	medium
Rectum	tissue	7.4	low
Colon	tissue	7.1	low
Stomach 1	tissue	7.0	medium
Tonsil	tissue	5.6	low
Esophagus	tissue	5.1	medium
Breast	tissue	4.8	low
Lymph node	tissue	4.6	low
Salivary gland	tissue	4.6	low
Appendix	tissue	4.4	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (264.1), Ventromedial nucleus (254.0), Dorsomedial nucleus (222.8), Medial dorsal thalamic nucleus (217.7), Arcuate nucleus (217.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ABAT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 95 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4729	99.69	72.18	4233

Functional genomics

gnomAD constraint: pLI 1.18e-10, LOEUF 0.871, missense Z 0.753 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000268251 — one region, missense o/e 0.96. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Marked differences in platelet uptake of GABA and activity of catabolic enzyme GABA-T between patients with generalized and localization-related epileptic syndromes. May indicate an impairment in function of brain GABAergic systems. (PMID:12694932)
• results suggest that the Cys321 residue is essential for the catalytic function of GABAT, and that it is involved in the formation of a disulfide link between two monomers of human brain GABAT (PMID:15528998)
• lysine 357 is essential for catalytic function of brain GABA transaminase, and is involved in binding PLP at the active site (PMID:15650327)
• Analysis of the autistic disorder susceptibility locus suggests an association on chromosome 16p between GRIN2A and ABAT. (PMID:15830322)
• excessive prenatal GABA exposure in the central nervous system (CNS) is responsible for the clinical manifestations of GABA transaminase deficiency [case report] (PMID:20052547)
• direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control in gastro esophageal reflux disease (PMID:21552517)
• Findings point to a possible role of ABAT gene-regulated GABA catabolism for an altered processing of somatosensory stimuli as a potential vulnerability marker for affective disorders. (PMID:22225676)
• A-to-G transition at nucleotide 754 of the human ABAT gene identified in lymphoblast cDNA (c.754A>G) results in substitution of an invariant arginine at amino acid 220 by lysine (p.Arg220Lys). This point mutation results in destabilization of the binding of pyridoxal-5’-phosphate to GABA-transaminase (required for transamination of GABA to succinic semialdehyde) and thus results in GABA-transaminase deficiency. (PMID:25485164)
• This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance. (PMID:25771305)
• ABAT SNP rs1641025 is a potential candidate locus for responsiveness to opioid analgesics in patients with cancer pain. (PMID:30277654)
• Exploring the Genetic Association of the ABAT Gene with Alzheimer’s Disease. (PMID:33404980)
• ABAT targeted by miR-183-5p regulates cell functions in liver cancer. (PMID:34742920)
• Effects of UGT1A, CYP2C9/19 and ABAT polymorphisms on plasma concentration of valproic acid in Chinese epilepsy patients. (PMID:36718958)
• A crucial exosome-related gene pair (AAMP and ABAT) is associated with inflammatory cells in intervertebral disc degeneration. (PMID:37122729)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	abat	ENSDARG00000006031
mus_musculus	Abat	ENSMUSG00000057880
rattus_norvegicus	Abat	ENSRNOG00000002636
drosophila_melanogaster	Gabat	FBGN0036927
caenorhabditis_elegans		WBGENE00001794

Paralogs (4): OAT (ENSG00000065154), AGXT2 (ENSG00000113492), ETNPPL (ENSG00000164089), PHYKPL (ENSG00000175309)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2443582) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased susceptibility to experimental autoimmune encephalomyelitis	1
decreased T cell proliferation	1
abnormal CD4-positive T cell differentiation	1
abnormal T-helper 1 cell differentiation	1
abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology	1
abnormal T-helper 17 cell differentiation	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mycobacterium tuberculosis variant bovis AF2122/97	P63510	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WQ76	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WQ77	100.0%	Diamond
Bos taurus	Q9BGI0	96.6%	Diamond
Sus scrofa	P80147	94.8%	Diamond
Amycolatopsis lactamdurans	Q05174	81.4%	Diamond
Saccharomyces cerevisiae S288C	P17649	77.1%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CJ86	77.1%	Diamond
Aspergillus nidulans FGSC A4	P14010	57.4%	Diamond
Dictyostelium discoideum	Q55FI1	57.3%	Diamond
Schizosaccharomyces pombe 972h-	O13837	57.1%	Diamond
Mycosarcoma maydis	P49604	57.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TMEM186	protein-coding	25880
METTL22	protein-coding	79091
TMEM114	protein-coding	283953
PMM2	protein-coding	5373
CARHSP1-DT	ncRNA	119545623
CARHSP1	protein-coding	23589

Protein

Protein identifiers

4-aminobutyrate aminotransferase, mitochondrial — P80404 (reviewed: P80404)

Alternative names: (S)-3-amino-2-methylpropionate transaminase, GABA aminotransferase, Gamma-amino-N-butyrate transaminase, L-AIBAT

All UniProt accessions (10): P80404, H3BMJ9, H3BNQ7, H3BP74, H3BP84, H3BPW8, H3BRJ1, H3BRN4, H3BRT1, X5D8S1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Liver > pancreas > brain > kidney > heart > placenta.

Disease relevance. GABA-transaminase deficiency (GABATD) [MIM:613163] An enzymatic deficiency resulting in psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. GABATD inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 [2Fe-2S] cluster per homodimer.

Similarity. Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.

RefSeq proteins (20): NP_000654, NP_001120920, NP_001373529, NP_001373530, NP_001373531, NP_001373532, NP_001373533, NP_001373534, NP_001373535, NP_001373536, NP_001373537, NP_001373538, NP_001373539, NP_001373540, NP_001373541, NP_001373542, NP_001373543, NP_001373544, NP_001373545, NP_065737* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004631	4NH2But_aminotransferase_euk	Family
IPR005814	Aminotrans_3	Family
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR049704	Aminotrans_3_PPA_site	Conserved_site

Pfam: PF00202

Enzyme classification (BRENDA)

• EC 2.6.1.19 — 4-aminobutyrate-2-oxoglutarate transaminase (BRENDA: 34 organisms, 110 substrates, 209 inhibitors, 111 Km, 46 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-AMINOBUTANOATE	0.077–146	35
2-OXOGLUTARATE	0.0021–46	24
BETA-ALANINE	1.05–18	4
PYRUVATE	0.0188–0.24	4
GLYOXYLATE	0.0165–0.11	3
(4R)-4-AMINO-1-CYCLOPENTENE-1-CARBOXYLIC ACID	0.1–1.6	2
(R)-4-AMINO-3-FLUOROBUTANOIC ACID	0.059	1
(R,S)-4-AMINO-3-FLUOROBUTANOIC ACID	0.045	1
1H-TETRAZOLE-5-BUTANAMINE	8	1
1H-TETRAZOLE-5-ETHANAMINE	2.3	1
1H-TETRAZOLE-5-PROPANAMINE	2.4	1
3-AMINOPROPANESULFONATE	8.5	1
4-(AMINOMETHYL)-1H-PYRROLE-2-CARBOXYLIC ACID	1.4	1
4-(AMINOMETHYL)FURAN-2-CARBOXYLIC ACID	0.31	1
4-(AMINOMETHYL)FURAN-3-CARBOXYLIC ACID	2.8	1

Catalyzed reactions (Rhea)

• (S)-3-amino-2-methylpropanoate + 2-oxoglutarate = 2-methyl-3-oxopropanoate + L-glutamate (RHEA:13993)
• 4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate (RHEA:23352)

UniProt features (33 total): sequence conflict 12, modified residue 10, binding site 5, sequence variant 2, transit peptide 1, chain 1, disulfide bond 1, mutagenesis site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80404-F1	93.91	0.92

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5)

Position	Role
163	[2Fe-2S] cluster
164–165	pyridoxal 5’-phosphate
166	[2Fe-2S] cluster
220	substrate
381	pyridoxal 5’-phosphate

Post-translational modifications (10)

Type	Positions
N6-acetyllysine	279, 318, 413, 452, 470, 252
N6-(pyridoxal phosphate)lysine	357
N6-succinyllysine	413, 231, 252

Disulfide bonds (1)

Type	Positions
Interchain	321

Mutagenesis-validated functional residues (1)

Position	Phenotype
321	loss of 4-aminobutyrate aminotransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-916853	Degradation of GABA	curated
R-HSA-888590	GABA synthesis, release, reuptake and degradation	—
R-HSA-112316	Neuronal System	—
R-HSA-112310	Neurotransmitter release cycle	—
R-HSA-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 417 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_HINDBRAIN_DEVELOPMENT, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_ACID_SECRETION, MODULE_274, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_COCAINE, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GGGNRMNNYCAT_UNKNOWN, RORA1_01

GO Biological Process (23): response to hypoxia (GO:0001666), copulation (GO:0007620), locomotory behavior (GO:0007626), response to xenobiotic stimulus (GO:0009410), GABA biosynthetic process (GO:0009449), GABA catabolic process (GO:0009450), response to iron ion (GO:0010039), negative regulation of gamma-aminobutyric acid secretion (GO:0014053), cerebellum development (GO:0021549), positive regulation of heat generation (GO:0031652), positive regulation of insulin secretion (GO:0032024), negative regulation of dopamine secretion (GO:0033602), response to nicotine (GO:0035094), exploration behavior (GO:0035640), response to cocaine (GO:0042220), response to ethanol (GO:0045471), negative regulation of blood pressure (GO:0045776), positive regulation of dopamine metabolic process (GO:0045964), nervous system process (GO:0050877), positive regulation of uterine smooth muscle contraction (GO:0070474), positive regulation of inhibitory postsynaptic potential (GO:0097151), positive regulation of prolactin secretion (GO:1902722), positive regulation of aspartate secretion (GO:1904450)

GO Molecular Function (9): pyridoxal phosphate binding (GO:0030170), succinate-semialdehyde dehydrogenase binding (GO:0032145), 4-aminobutyrate:2-oxoglutarate transaminase activity (GO:0034386), identical protein binding (GO:0042802), metal ion binding (GO:0046872), (S)-3-amino-2-methylpropionate:2-oxoglutarate transaminase activity (GO:0047298), iron-sulfur cluster binding (GO:0051536), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), 4-aminobutyrate transaminase complex (GO:0032144)

Reactome top-level categories

4 top-level categories:

Category	Pathways
GABA synthesis, release, reuptake and degradation	1
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter release cycle	1

GO top-level categories

53 GO namespaces:

Category	Terms
behavior	2
response to chemical	2
transaminase activity	2
response to stress	1
response to decreased oxygen levels	1
mating behavior	1
amino acid biosynthetic process	1
non-proteinogenic amino acid biosynthetic process	1
amino acid catabolic process	1
non-proteinogenic amino acid catabolic process	1
response to metal ion	1
gamma-aminobutyric acid secretion	1
regulation of gamma-aminobutyric acid secretion	1
negative regulation of organic acid transport	1
negative regulation of secretion	1
negative regulation of amino acid transport	1
metencephalon development	1
animal gross anatomical part developmental process	1
heat generation	1
regulation of heat generation	1
positive regulation of multicellular organismal process	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
dopamine secretion	1
regulation of dopamine secretion	1
negative regulation of catecholamine secretion	1
response to alkaloid	1
response to oxygen-containing compound	1
response to alcohol	1
regulation of blood pressure	1
positive regulation of amine metabolic process	1
regulation of dopamine metabolic process	1
dopamine metabolic process	1
system process	1
positive regulation of smooth muscle contraction	1
uterine smooth muscle contraction	1
regulation of uterine smooth muscle contraction	1
anion binding	1
vitamin B6 binding	1
enzyme binding	1
protein binding	1
cation binding	1
metal cluster binding	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
intracellular protein-containing complex	1
transferase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 36 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
4-aminobutyrate transaminase complex	CC	direct assay
mitochondrion	CC	direct assay
4-aminobutyrate:2-oxoglutarate transaminase activity	MF	direct assay
identical protein binding	MF	physical interaction
pyridoxal phosphate binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,156 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABAT	ALDH5A1	P51649	847
ABAT	GAD1	Q99259	699
ABAT	GAD2	Q05329	634
ABAT	GOT1	P17174	561
ABAT	ALDH6A1	Q02252	560
ABAT	GLUD2	P49448	465
ABAT	ASS1	P00966	443
ABAT	GLUL	P15104	442
ABAT	PPAT	Q06203	441
ABAT	AGXT	P21549	441
ABAT	UPB1	Q9UBR1	431
ABAT	ALDH4A1	P30038	424
ABAT	MAN1C1	Q9NR34	419
ABAT	GLUD1	P00367	416
ABAT	PDXK	O00764	412

IntAct

Human interaction partners of ABAT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
ARMH1	physical association	0.400	2
CRK	physical association	0.400	1

BioGRID (86 interactions; top human partners by supporting records): SEC22C (Affinity Capture-MS; 3 records), ALDH7A1 (Co-fractionation; 2 records), ASGR1 (Affinity Capture-MS; 2 records), C1orf228 (Affinity Capture-MS; 2 records), DSTN (Co-fractionation; 2 records), ETFA (Co-fractionation; 2 records), FAHD1 (Co-fractionation; 2 records), PGM2 (Co-fractionation; 2 records), SOD2 (Co-fractionation; 2 records), ZSCAN29 (Affinity Capture-MS; 2 records), ACP6 (Co-fractionation), ADSL (Co-fractionation), AKR1B1 (Co-fractionation), AKR1C2 (Co-fractionation), AKR1C3 (Co-fractionation)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ABAT homodimer	1	ABAT

Disease & clinical

Genetic variants

Variant evidence for ABAT: 898 ClinVar records (53 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

898 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	23
Uncertain significance	382
Likely benign	326
Benign	60

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 53 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
635252	NM_020686.6(ABAT):c.168+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
16216	NM_020686.6(ABAT):c.659G>A (p.Arg220Lys)	Pathogenic	criteria provided, single submitter	2
162035	NM_020686.6(ABAT):c.1433T>C (p.Leu478Pro)	Pathogenic	criteria provided, single submitter	2
162037	NM_000663.4(ABAT):c.199-?_316+?del	Pathogenic	criteria provided, single submitter	1
635253	NM_020686.6(ABAT):c.454C>T (p.Pro152Ser)	Pathogenic	criteria provided, single submitter	1
635254	NM_020686.6(ABAT):c.1393G>C (p.Gly465Arg)	Pathogenic	criteria provided, single submitter	1
635255	NM_020686.6(ABAT):c.638T>G (p.Phe213Cys)	Pathogenic	criteria provided, single submitter	1
2011985	NM_020686.6(ABAT):c.378dup (p.Asn127fs)	Pathogenic	criteria provided, single submitter	1
2012439	NM_020686.6(ABAT):c.274C>T (p.Arg92Ter)	Pathogenic	criteria provided, single submitter	1
2131506	NM_020686.6(ABAT):c.829_832del (p.Leu276_Ile277insTer)	Pathogenic	criteria provided, single submitter	1
3376949	NM_020686.6(ABAT):c.1031G>A (p.Trp344Ter)	Pathogenic	criteria provided, single submitter	1
3659859	NM_020686.6(ABAT):c.658_659del (p.Arg220fs)	Pathogenic	criteria provided, single submitter	1
4713129	NM_020686.6(ABAT):c.1145G>A (p.Trp382Ter)	Pathogenic	criteria provided, single submitter	1
4736587	NM_020686.6(ABAT):c.405del (p.Pro136fs)	Pathogenic	criteria provided, single submitter	1
191066	NM_020686.6(ABAT):c.709G>A (p.Asp237Asn)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ABAT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 1,567):

Position(s)	Effect	Δscore	Sites
16:8674712–8674713	donor_loss	1.0000	2
16:8735810–8735811	donor_loss	1.0000	5
16:8745999–8746000	acceptor_loss	1.0000	4
16:8746099–8746100	donor_loss	1.0000	5
16:8750420	acceptor_gain	1.0000
16:8750540–8750541	donor_loss	1.0000	5
16:8764067–8764068	acceptor_loss	1.0000	6
16:8764150–8764151	donor_loss	1.0000	5
16:8764736–8764737	acceptor_loss	1.0000	6
16:8766271–8766272	donor_loss	1.0000	4

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.11e-08
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	2.14e-05
Lung Adenocarcinoma (TCGA)	favorable	6.68e-05
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000542

Disease associations

OMIM: gene MIM:137150 | disease phenotypes: MIM:613163, MIM:212065

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
GABA aminotransaminase deficiency	Definitive	Autosomal recessive	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (13 panels, 13 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

13 panels:

Panel	Rating
DDG2P	green
Dystonia, chorea or related movement disorder, childhood onset	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial DNA maintenance disorder	green
Mitochondrial disorders	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): GABA aminotransaminase deficiency (MONDO:0013166), Landau-Kleffner syndrome (MONDO:0009509), PMM2-congenital disorder of glycosylation (MONDO:0008907)

Orphanet (5): Gamma-aminobutyric acid transaminase deficiency (Orphanet:2066), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Developmental and epileptic encephalopathy with spike-wave activation in sleep (Orphanet:725), Landau-Kleffner syndrome (Orphanet:98818), PMM2-CDG (Orphanet:79318)

HPO phenotypes

34 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000098	Tall stature
HP:0000278	Retrognathia
HP:0000494	Downslanted palpebral fissures
HP:0000845	Elevated circulating growth hormone concentration
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001274	Agenesis of corpus callosum
HP:0001321	Cerebellar hypoplasia
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002059	Cerebral atrophy
HP:0002353	EEG abnormality
HP:0002415	Leukodystrophy
HP:0003623	Neonatal onset
HP:0003819	Death in childhood
HP:0007266	Cerebral dysmyelination
HP:0007272	Progressive psychomotor deterioration
HP:0007291	Posterior fossa cyst
HP:0008872	Feeding difficulties in infancy
HP:0010851	EEG with burst suppression
HP:0011344	Severe global developmental delay
HP:0011968	Feeding difficulties
HP:0025430	High-pitched cry
HP:0032531	Elevated CSF gamma-aminobutyric acid concentration
HP:0200134	Epileptic encephalopathy
HP:0410053	Elevated circulating GABA concentration
HP:0500253	Increased level of gamma-aminobutyric acid in urine

GWAS associations

4 associations:

Study	Trait	p-value
GCST007106_1	Response to opioid analgesics in cancer (pain decrease)	2e-8
GCST005312_36	Menopause (age at onset)	3e-8
GCST006460_12	Bronchopulmonary dysplasia in preterm infants	3e-6
GCST002324_12	Anger	8e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0003015	aggressive behavior
EFO:0004704	age at menopause
EFO:0008541	response to opioid

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D018887	Landau-Kleffner Syndrome	C10.228.140.490.493.500
C535739	Congenital disorder of glycosylation type 1A *(supp.)*
C535407	Gamma aminobutyric acid transaminase deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2044 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ABAT protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
VIGABATRIN	Small molecule	4

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1731017	valproic acid	Metabolism/PK	Genotype GG is associated with increased exposure to valproic acid in people with Epilepsy as compared to genotype AA.	PMID:36718958

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — GABA turnover

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
4-acryloylphenol	Inhibition	5.26	pIC50
CPP-115	Inhibition	5.01	pKi
vigabatrin	Irreversible inhibition	3.07	pKi

Binding affinities (BindingDB)

33 measured of 48 human assays (49 total across all organisms); most potent 33 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(4-hydroxyphenyl)prop-2-en-1-one	IC50	5480 nM
(2Z)-4-ammonio-2-(fluoromethyl)but-2-enoate	KI	9000 nM
CHEMBL4746439	IC50	9690 nM
CHEMBL4740703	IC50	12200 nM
4-(aminomethyl)phenol	IC50	15400 nM
4-hydroxy-3-nitrobenzaldehyde	IC50	15500 nM
4-hydroxybenzaldehyde	IC50	16500 nM
4-hydroxy-3-methoxybenzaldehyde	IC50	17100 nM
CHEMBL4750359	IC50	18400 nM
CHEMBL5408239	IC50	19200 nM
CHEMBL5404015	IC50	31000 nM
N-Phenylthiohydantoic acid	KI	91000 nM
5-Amino-cyclohex-3-enecarboxylic acid	KI	100000 nM
2-Amino-cyclohex-3-enecarboxylic acid	KI	125000 nM
1-(4-hydroxyphenyl)propan-1-one	IC50	151000 nM
(2S,4S)-4-Aminotetrahydrothiophene-2-carboxylic acid	KI	182000 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
methyl (2S,4S)-4-aminothiolane-2-carboxylate	KI	182000 nM	US-10800753: Tetrahydrothiophene-based GABA aminotransferase inactivators and analogs thereof for treating neurological disorders
1-(4-hydroxyphenyl)ethanone	IC50	1.71e+06 nM
(2R,4S)-4-Aminotetrahydrothiophene-2-carboxylic acid	KI	2.23e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
5-Amino-cyclohex-3-enecarboxylic acid	KI	2.3e+06 nM
(4S)-4-Aminotetrahydrothiophene-2-carboxylic acid 1,1-dioxide	KI	3.2e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(4S)-4-amino-1,1-dioxothiolane-2-carboxylic acid	KI	3.2e+06 nM	US-10800753: Tetrahydrothiophene-based GABA aminotransferase inactivators and analogs thereof for treating neurological disorders
4-Amino-hex-5-enoic acid	KI	3.2e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
VIGABATRIN	KI	3.2e+06 nM	US-10800753: Tetrahydrothiophene-based GABA aminotransferase inactivators and analogs thereof for treating neurological disorders
(2S,4R)-4-azaniumylthiolane-2-carboxylate	KI	3.3e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(2S,4R)-4-aminothiolane-2-carboxylic acid	KI	3.3e+06 nM	US-10800753: Tetrahydrothiophene-based GABA aminotransferase inactivators and analogs thereof for treating neurological disorders
(2R,4R)-4-azaniumylthiolane-2-carboxylate	KI	3.4e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(2R,4R)-4-aminothiolane-2-carboxylic acid	KI	3.4e+06 nM	US-10800753: Tetrahydrothiophene-based GABA aminotransferase inactivators and analogs thereof for treating neurological disorders
3-Aminomethyl-2,6-difluoro-phenol	KI	6.3e+06 nM
(4R)-4-azaniumyl-1,1-dioxothiolane-2-carboxylate	KI	7.5e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(4R)-4-amino-1,1-dioxothiolane-2-carboxylic acid	KI	7.5e+06 nM	US-10800753: Tetrahydrothiophene-based GABA aminotransferase inactivators and analogs thereof for treating neurological disorders
4-(ammoniomethyl)-2,6-difluorobenzenolate	KI	1.1e+07 nM
2-Amino-cyclohex-3-enecarboxylic acid	KI	1.3e+07 nM

ChEMBL bioactivities

7 potent at pChembl≥5 of 17 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.65	Ki	222.4	nM	BAY-3827
5.68	Ki	2100	nM	IPP/CNRS-A017
5.59	Ki	2560	nM	BI 2545
5.58	Ki	2623	nM	BI-605906
5.26	IC50	5480	nM	CHEMBL378577
5.05	Ki	9000	nM	CHEMBL353363
5.01	IC50	9690	nM	CHEMBL4746439

PubChem BioAssay actives

3 with measured affinity, of 128 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(4-hydroxyphenyl)prop-2-en-1-one	260086: Inhibitory activity against GABAT	ic50	5.4800	uM
(Z)-4-amino-2-(fluoromethyl)but-2-enoic acid	73360: Compound was tested for the inhibitory effect against Gamma-amino-N-butyrate transaminase from bacteria	ki	9.0000	uM
(3S)-3-amino-4-(difluoromethylidene)cyclopentene-1-carboxylic acid	2030300: Inhibition of GABA-AT (unknown origin)	ic50	9.6900	uM

CTD chemical–gene interactions

76 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects methylation, decreases expression, decreases methylation	9
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, decreases methylation	8
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases methylation	5
Cyclosporine	decreases expression	4
bisphenol A	affects expression, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects expression, increases expression, affects cotreatment	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Leflunomide	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Ethinyl Estradiol	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Vigabatrin	increases abundance, decreases activity	2
Particulate Matter	affects expression, increases abundance	2
GSK-J4	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1

ChEMBL screening assays

41 unique, capped per target: 41 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2208624	Binding	Activity of GABA aminotransferase	Synopsis of some recent tactical application of bioisosteres in drug design. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SA89	HAP1 ABAT (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

26 trials:

NCT	Phase	Status	Title
NCT04925960	Phase 3	TERMINATED	Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG
NCT03414970	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT05549219	Phase 2	COMPLETED	24-Week Study to Assess the PD, Safety, Tolerability, and PK of GLM101 in Participants With PMM2-CDG
NCT06657859	Phase 2	ENROLLING_BY_INVITATION	Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients
NCT00461344	Phase 2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	Phase 2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02904265	Phase 2/3	TERMINATED	Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome
NCT01335425	Not specified	COMPLETED	The Rolandic Epilepsy/ESES/Landau-Kleffner Syndrome and Correlation With Language Impairment Study
NCT04592679	Not specified	COMPLETED	Cost-Effectiveness Analysis of a Rehabilitation Protocol With FES Cycling in Persons With Complete SCI
NCT04679389	Phase 2/3	TERMINATED	Acetazolamide Efficacy in Ataxia in PMM2-CDG
NCT06892288	Phase 2/3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
NCT03173300	Not specified	COMPLETED	Natural History Study Protocol in PMM2-CDG (CDG-Ia)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT04251325	Not specified	UNKNOWN	Socio-demographic Characteristics of Basic Life Support Course Participants
NCT04353089	Not specified	UNKNOWN	Geographical Association Between Basic Life Support Courses, Bystander Cardiopulmonary Resuscitation and Survival
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT00637364	Phase 1/2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	Phase 1/2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	Early Phase 1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	Early Phase 1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT07628634	Early Phase 1	RECRUITING	Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors
NCT01208974	Not specified	COMPLETED	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ABAT across ~30M SureChEMBL compounds — explore on Sugi Predict.