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): 893 total — 30 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• 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: 21 — 14 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

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

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.

FANTOM5 promoters (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

297 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting ABAT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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)

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), 2 shown:

• (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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 163; 164–165 (in other chain); 166; 220; 381

Post-translational modifications (10): 279, 318, 357, 413, 413, 452, 470, 231, 252, 252

Disulfide bonds (1): 321

Mutagenesis-validated functional residues (1):

Position	Phenotype
321	loss of 4-aminobutyrate aminotransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-916853	Degradation of GABA

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 (24): response to hypoxia (GO:0001666), copulation (GO:0007620), locomotory behavior (GO:0007626), response to xenobiotic stimulus (GO:0009410), obsolete GABA metabolic process (GO:0009448), 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

Rollup of top-1 pathways:

Category	Pathways
GABA synthesis, release, reuptake and degradation	1

GO top-level categories

Rollup of top GO terms by namespace:

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
anatomical structure development	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
anion binding	1
vitamin B6 binding	1
enzyme binding	1
protein binding	1

Protein interactions and networks

STRING

1602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABAT	ALDH5A1	P51649	856
ABAT	GAD1	Q99259	642
ABAT	GAD2	Q05329	635
ABAT	ALDH6A1	Q02252	573
ABAT	GOT1	P17174	571
ABAT	GLUD2	P49448	529
ABAT	GLUL	P15104	518
ABAT	GLUD1	P00367	503
ABAT	GOT1L1	Q8NHS2	492
ABAT	PPAT	Q06203	462
ABAT	MAOB	P27338	448
ABAT	ASS1	P00966	446
ABAT	MAOA	P21397	441
ABAT	AGXT	P21549	425
ABAT	ALDH18A1	P54886	404

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ASGR1	PTPN2	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
SERINC1	LGALS3	psi-mi:“MI:0914”(association)	0.530
CRK	ABAT	psi-mi:“MI:0915”(physical association)	0.400
ARMH1	ABAT	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZSCAN29	GSDME	psi-mi:“MI:0914”(association)	0.350
SEC22C	ACADS	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
SYBU	SNPH	psi-mi:“MI:0914”(association)	0.350
EPHX1	RAB34	psi-mi:“MI:0914”(association)	0.350

BioGRID (84): ABAT (Affinity Capture-MS), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ABAT (Co-fractionation), ADSL (Co-fractionation), AKR1B1 (Co-fractionation), CBS (Co-fractionation), ENO1 (Co-fractionation)

ESM2 similar proteins: A3KN12, O88958, P21265, P21343, P30566, P36959, P38024, P50554, P50990, P54822, P61922, P78371, P80147, P80314, P80404, P82197, Q04447, Q0II59, Q259G4, Q2KIG0, Q3ZBF0, Q3ZBH0, Q3ZCI9, Q41141, Q4R4U1, Q4R5J0, Q4R5Y2, Q4R6F8, Q5E982, Q5R5F8, Q5RAP1, Q5XIM9, Q5ZMA6, Q64422, Q6EE31, Q6IA69, Q711T7, Q7XPW5, Q7ZV22, Q812E8

Diamond homologs: O13837, P14010, P17649, P49604, P50554, P61922, P80147, P80404, Q01767, Q05174, Q21217, Q55FI1, Q6CJ86, Q9BGI0, A1BJG8, A1RQR5, A4IRG2, A6GYW4, A6UWB3, A9KP86, B1YBL3, B2UX41, B5BA72, B7N584, B7NT29, B9MRJ7, C1A7K7, E6SRG2, P0C2D9, P18492, P31593, P31893, P42799, P53555, P63510, P9WQ76, P9WQ77, Q0AZ36, Q0TQG7, Q2NF42

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	25
Uncertain significance	378
Likely benign	325
Benign	64

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
144298	GRCh38/hg38 16p13.3-13.13(chr16:46766-11525516)x3	Pathogenic
162035	NM_020686.6(ABAT):c.1433T>C (p.Leu478Pro)	Pathogenic
162037	NM_000663.4(ABAT):c.199-?_316+?del	Pathogenic
16216	NM_020686.6(ABAT):c.659G>A (p.Arg220Lys)	Pathogenic
16217	ABAT, 3-PRIME DELETION	Pathogenic
1807793	GRCh37/hg19 16p13.3-11.2(chr16:4380767-30445350)x3	Pathogenic
2011985	NM_020686.6(ABAT):c.378dup (p.Asn127fs)	Pathogenic
2012439	NM_020686.6(ABAT):c.274C>T (p.Arg92Ter)	Pathogenic
2131506	NM_020686.6(ABAT):c.829_832del (p.Leu276_Ile277insTer)	Pathogenic
2426571	NC_000016.9:g.(?8839838)(8870367_?)del	Pathogenic
3063402	GRCh37/hg19 16p13.2(chr16:8772448-8949474)x1	Pathogenic
3243409	NC_000016.9:g.(?8829597)(9923529_?)del	Pathogenic
3339972	NC_000016.9:g.(?8768473)(8878428_?)del	Pathogenic
3376949	NM_020686.6(ABAT):c.1031G>A (p.Trp344Ter)	Pathogenic
3659859	NM_020686.6(ABAT):c.658_659del (p.Arg220fs)	Pathogenic
395719	GRCh37/hg19 16p13.3-13.2(chr16:78801-9169448)	Pathogenic
438385	NM_000663.5:c.199_316del	Pathogenic
438386	NM_020686.6(ABAT):c.817-2A>G	Pathogenic
438387	NM_020686.6(ABAT):c.1460T>C (p.Leu487Pro)	Pathogenic
442872	GRCh37/hg19 16p13.3-12.3(chr16:85880-19806921)x3	Pathogenic
443183	GRCh37/hg19 16p13.3-12.2(chr16:85880-22442007)x3	Pathogenic
443477	GRCh37/hg19 16p13.3-13.2(chr16:85880-9883129)x3	Pathogenic
4713129	NM_020686.6(ABAT):c.1145G>A (p.Trp382Ter)	Pathogenic
4736587	NM_020686.6(ABAT):c.405del (p.Pro136fs)	Pathogenic
635252	NM_020686.6(ABAT):c.168+1G>A	Pathogenic
635253	NM_020686.6(ABAT):c.454C>T (p.Pro152Ser)	Pathogenic
635254	NM_020686.6(ABAT):c.1393G>C (p.Gly465Arg)	Pathogenic
635255	NM_020686.6(ABAT):c.638T>G (p.Phe213Cys)	Pathogenic
661750	NC_000016.10:g.(?8779459)(8847845_?)del	Pathogenic
813717	GRCh37/hg19 16p13.3-11.2(chr16:5805001-34230001)	Pathogenic

SpliceAI

3015 predictions. Top by Δscore:

Variant	Effect	Δscore
16:8674709:GAG:G	donor_gain	1.0000
16:8674709:GAGGT:G	donor_loss	1.0000
16:8674710:AGGT:A	donor_loss	1.0000
16:8674711:GGTG:G	donor_loss	1.0000
16:8674712:GTGA:G	donor_loss	1.0000
16:8674713:T:G	donor_loss	1.0000
16:8735806:CCTGG:C	donor_loss	1.0000
16:8735807:CTGG:C	donor_loss	1.0000
16:8735808:TGGT:T	donor_loss	1.0000
16:8735809:GGTAA:G	donor_loss	1.0000
16:8735810:G:T	donor_loss	1.0000
16:8735811:TAAG:T	donor_loss	1.0000
16:8745996:TGCA:T	acceptor_loss	1.0000
16:8745997:GCA:G	acceptor_loss	1.0000
16:8745998:CA:C	acceptor_loss	1.0000
16:8745999:A:AG	acceptor_gain	1.0000
16:8745999:A:AT	acceptor_loss	1.0000
16:8745999:AG:A	acceptor_gain	1.0000
16:8746000:G:GC	acceptor_gain	1.0000
16:8746000:GG:G	acceptor_gain	1.0000
16:8746095:TCAGG:T	donor_loss	1.0000
16:8746099:G:GG	donor_gain	1.0000
16:8746099:GTG:G	donor_loss	1.0000
16:8746100:T:G	donor_loss	1.0000
16:8748107:GGA:G	acceptor_gain	1.0000
16:8750419:A:AG	acceptor_gain	1.0000
16:8750420:A:AG	acceptor_gain	1.0000
16:8750421:G:GG	acceptor_gain	1.0000
16:8750536:ATAGG:A	donor_loss	1.0000
16:8750537:TAGGT:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000018713 (16:8778851 C>G,T), RS1000020789 (16:8700546 G>C), RS1000027811 (16:8750025 G>A), RS1000038622 (16:8720864 G>A), RS1000052073 (16:8758885 G>C), RS1000067313 (16:8730544 C>CAG), RS1000074117 (16:8725800 T>A,C), RS1000075393 (16:8783456 G>C), RS1000085656 (16:8754604 C>T), RS1000134668 (16:8784071 A>C), RS1000155147 (16:8736397 G>A,T), RS1000186166 (16:8673290 T>A,C), RS1000216031 (16:8767739 G>A), RS1000223005 (16:8676564 C>A,G,T), RS1000223666 (16:8734044 C>A,T)

Disease associations

OMIM: gene MIM:137150 | disease phenotypes: MIM:613163, MIM:212065, MIM:209920, MIM:601098, MIM:613458

GenCC curated gene-disease

Disease	Classification	Inheritance
GABA aminotransaminase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Moderate	AR

Mondo (8): GABA aminotransaminase deficiency (MONDO:0013166), Landau-Kleffner syndrome (MONDO:0009509), PMM2-congenital disorder of glycosylation (MONDO:0008907), MHC class II deficiency (MONDO:0008855), Charcot-Marie-Tooth disease type 1C (MONDO:0010995), chromosome 16p13.3 duplication syndrome (MONDO:0013273), breast ductal adenocarcinoma (MONDO:0005590), microcephaly (MONDO:0001149)

Orphanet (8): 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), Charcot-Marie-Tooth disease type 1C (Orphanet:101083), Immunodeficiency by defective expression of MHC class II (Orphanet:572), 16p13.3 microduplication syndrome (Orphanet:96078)

HPO phenotypes

34 total (30 of 34 shown, 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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002324_12	Anger	8.000000e-06
GCST005312_35	Menopause (age at onset)	3.000000e-08
GCST006460_12	Bronchopulmonary dysplasia in preterm infants	3.000000e-06
GCST007106_2	Response to opioid analgesics in cancer (pain decrease)	2.000000e-08

EFO canonical traits (3, from GWAS)

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

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D018887	Landau-Kleffner Syndrome	C10.228.140.490.493.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537079	Bare lymphocyte syndrome 2 (supp.)
C537984	Charcot-Marie-Tooth disease, Type 1C (supp.)
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)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1731017	ABAT		0.00	0

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)

7 measured of 7 human assays (7 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,4S)-4-Aminotetrahydrothiophene-2-carboxylic acid	KI	182000 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(2R,4S)-4-Aminotetrahydrothiophene-2-carboxylic acid	KI	2.23e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(4S)-4-Aminotetrahydrothiophene-2-carboxylic acid 1,1-dioxide	KI	3.2e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
4-Amino-hex-5-enoic acid	KI	3.2e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(2S,4R)-4-azaniumylthiolane-2-carboxylate	KI	3.3e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(2R,4R)-4-azaniumylthiolane-2-carboxylate	KI	3.4e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators
(4R)-4-azaniumyl-1,1-dioxothiolane-2-carboxylate	KI	7.5e+06 nM	US-10189807: Tetrahydrothiophene-based GABA aminotransferase inactivators

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	affects methylation, decreases expression, decreases methylation, increases methylation	8
Aflatoxin B1	increases methylation, affects expression, decreases expression, decreases 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	affects cotreatment, increases expression	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	increases expression, affects cotreatment	2
Vigabatrin	decreases activity, increases abundance	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	affects binding, decreases expression, increases activity	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)

41 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04925960	PHASE3	TERMINATED	Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT05549219	PHASE2	COMPLETED	24-Week Study to Assess the PD, Safety, Tolerability, and PK of GLM101 in Participants With PMM2-CDG
NCT06657859	PHASE2	ENROLLING_BY_INVITATION	Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	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	PHASE2/PHASE3	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	PHASE2/PHASE3	TERMINATED	Acetazolamide Efficacy in Ataxia in PMM2-CDG
NCT06892288	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
NCT03173300	Not specified	ACTIVE_NOT_RECRUITING	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	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	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
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers