ABAT

4-aminobutyrate aminotransferase

Basic information

Region (hg38): 16:8674595-8784575

Links

ENSG00000183044 ∙ NCBI:18 ∙ OMIM:137150 ∙ HGNC:23 ∙ Uniprot:P80404 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• GABA aminotransaminase deficiency (Limited), mode of inheritance: AR
• GABA aminotransaminase deficiency (Moderate), mode of inheritance: AR
• GABA aminotransaminase deficiency (Strong), mode of inheritance: AR
• GABA aminotransaminase deficiency (Supportive), mode of inheritance: AR
• developmental and epileptic encephalopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
GABA-transaminase deficiency	AR	Biochemical	The condition includes neonatal or early-onset neurologic sequelae, and medical management (with continuous flumazenil) has been described as beneficial in a patient with a milder phenotype	Biochemical; Neurologic	6148708; 4020531; 10407778; 27596361; 28411234

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABAT gene.

• Gamma-aminobutyric acid transaminase deficiency (627 variants)
• not provided (53 variants)
• Inborn genetic diseases (20 variants)
• not specified (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABAT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	102	6	111
missense	5	3	204	3	2	217
nonsense	2	4	2	1		9
start loss			1			1
frameshift	2	4	1			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	7	1			9
splice region			17	26	5	48
non coding			58	99	48	205
Total	10	18	273	205	56

Highest pathogenic variant AF is 0.00000657

Variants in ABAT

This is a list of pathogenic ClinVar variants found in the ABAT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-8674603-C-A		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jun 14, 2016)
16-8674626-C-G		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jan 13, 2018)
16-8674646-G-A		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jan 13, 2018)
16-8674701-G-T		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jan 12, 2018)
16-8735740-A-G		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jan 19, 2024)
16-8735741-T-TG		Gamma-aminobutyric acid transaminase deficiency	Likely pathogenic (May 20, 2023)
16-8735747-C-A			Uncertain significance (Dec 29, 2022)
16-8735752-T-C		Gamma-aminobutyric acid transaminase deficiency	Likely benign (Nov 27, 2023)
16-8735753-T-G		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jan 26, 2022)
16-8735757-C-T		Gamma-aminobutyric acid transaminase deficiency	Likely benign (Jul 30, 2023)
16-8735758-G-A		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Jul 19, 2022)
16-8735761-C-T		Gamma-aminobutyric acid transaminase deficiency	Likely pathogenic (Oct 31, 2023)
16-8735764-C-T		Gamma-aminobutyric acid transaminase deficiency • Inborn genetic diseases	Uncertain significance (Oct 24, 2022)
16-8735765-G-A		Gamma-aminobutyric acid transaminase deficiency • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 16, 2024)
16-8735769-G-A		not specified • Gamma-aminobutyric acid transaminase deficiency • ABAT-related disorder	Benign/Likely benign (Feb 01, 2024)
16-8735775-C-T		Gamma-aminobutyric acid transaminase deficiency	Likely benign (Dec 03, 2023)
16-8735781-C-G		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Oct 13, 2023)
16-8735783-A-T		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Apr 09, 2022)
16-8735784-G-A		Gamma-aminobutyric acid transaminase deficiency	Likely benign (May 15, 2022)
16-8735784-G-C		Gamma-aminobutyric acid transaminase deficiency • Inborn genetic diseases	Uncertain significance (Aug 22, 2022)
16-8735794-C-A		Gamma-aminobutyric acid transaminase deficiency • Inborn genetic diseases	Uncertain significance (Oct 18, 2022)
16-8735794-C-T		Gamma-aminobutyric acid transaminase deficiency	Conflicting classifications of pathogenicity (Jan 24, 2024)
16-8735795-G-A		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Oct 24, 2022)
16-8735795-G-T		Gamma-aminobutyric acid transaminase deficiency	Uncertain significance (Aug 20, 2021)
16-8735796-C-T		Gamma-aminobutyric acid transaminase deficiency	Likely benign (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABAT	protein_coding	protein_coding	ENST00000396600	15	110011

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00632	0.994	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.573	266	294	0.906	0.0000196	3317
Missense in Polyphen		57	99.401	0.57343		1030
Synonymous	-0.642	127	118	1.08	0.00000863	931
Loss of Function	3.29	9	27.7	0.325	0.00000140	317

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00	0.00
Finnish	0.0000933	0.0000924
European (Non-Finnish)	0.0000890	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Butanoate metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Carnosinuria, carnosinemia;Ureidopropionase deficiency;GABA-Transaminase Deficiency;3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Hydroxyglutric Aciduria (D And L Form);2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Malonyl-coa decarboxylase deficiency;Beta-Alanine Metabolism;Malonic Aciduria;Hypoacetylaspartia;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Propanoate Metabolism;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Aspartate Metabolism;Homocarnosinosis;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;Beta-Ketothiolase Deficiency;Canavan Disease;Alanine and aspartate metabolism;Valproic acid pathway;Alanine Aspartate Asparagine metabolism;Glutamate Glutamine metabolism;Neuronal System;valine degradation;Histidine metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Valine, leucine and isoleucine degradation;Arginine Proline metabolism;GABA shunt;Pyrimidine nucleotides nucleosides metabolism;Degradation of GABA;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Transmission across Chemical Synapses;4-aminobutyrate degradation;β-alanine degradation (Consensus)

Intolerance Scores

• loftool: 0.106
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.74

Haploinsufficiency Scores

• pHI: 0.410
• hipred: Y
• hipred_score: 0.554
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Abat

Gene ontology

• Biological process: response to hypoxia;aging;copulation;locomotory behavior;gamma-aminobutyric acid biosynthetic process;gamma-aminobutyric acid catabolic process;response to iron ion;negative regulation of gamma-aminobutyric acid secretion;cerebellum development;positive regulation of heat generation;positive regulation of insulin secretion;negative regulation of dopamine secretion;response to nicotine;exploration behavior;neurotransmitter catabolic process;response to ethanol;negative regulation of blood pressure;positive regulation of dopamine metabolic process;behavioral response to cocaine;positive regulation of uterine smooth muscle contraction;negative regulation of platelet aggregation;positive regulation of inhibitory postsynaptic potential;positive regulation of prolactin secretion;positive regulation of aspartate secretion
• Cellular component: mitochondrion;mitochondrial matrix;4-aminobutyrate transaminase complex;neuron projection
• Molecular function: 4-aminobutyrate transaminase activity;pyridoxal phosphate binding;succinate-semialdehyde dehydrogenase binding;4-aminobutyrate:2-oxoglutarate transaminase activity;protein homodimerization activity;metal ion binding;(S)-3-amino-2-methylpropionate transaminase activity;iron-sulfur cluster binding