GOT2

glutamic-oxaloacetic transaminase 2

Basic information

Region (hg38): 16:58707130-58734342

Links

ENSG00000125166 ∙ NCBI:2806 ∙ OMIM:138150 ∙ HGNC:4433 ∙ Uniprot:P00505 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 82 (Limited), mode of inheritance: AR
• developmental and epileptic encephalopathy, 82 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 82	AR	Neurologic	The condition can involve early-onset metabolic encephalopathy, and treatment with combined pyridoxine and serine has been described asresulting in improvement in seizures and mild developmental progress	Biochemical; Neurologic	31422819

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GOT2 gene.

• not provided (79 variants)
• Developmental and epileptic encephalopathy, 82 (14 variants)
• Inborn genetic diseases (12 variants)
• Early infantile epileptic encephalopathy with suppression bursts (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GOT2 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			1	8	9	18
missense		3	44	3	6	56
nonsense						0
start loss						0
frameshift			1			1
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region			1	3	2	6
non coding				11	4	15
Total	0	4	46	22	19

Variants in GOT2

This is a list of pathogenic ClinVar variants found in the GOT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-58708186-G-A			Likely benign (Oct 13, 2023)
16-58708208-C-T		Developmental and epileptic encephalopathy, 82	Uncertain significance (Mar 18, 2021)
16-58708213-G-A			Likely benign (Dec 11, 2023)
16-58708216-G-A			Benign (Jan 08, 2024)
16-58708220-G-C		not specified	Uncertain significance (Jun 13, 2023)
16-58708225-G-A			Likely benign (Feb 21, 2023)
16-58708250-T-C			Uncertain significance (Nov 15, 2022)
16-58708284-G-A			Likely benign (Oct 27, 2023)
16-58708286-C-T			Likely benign (Oct 03, 2023)
16-58708287-G-A			Likely benign (Jun 08, 2021)
16-58708301-G-C			Benign (Nov 02, 2023)
16-58708308-G-T			Likely benign (Feb 18, 2023)
16-58708310-A-C			Likely benign (Jul 25, 2023)
16-58709407-A-C			Likely benign (Jun 21, 2023)
16-58709417-C-T			Uncertain significance (Oct 24, 2022)
16-58709436-G-A			Uncertain significance (Dec 09, 2021)
16-58709461-C-T			Uncertain significance (Jun 18, 2022)
16-58709462-G-A			Benign (Jan 22, 2024)
16-58709472-T-C		not specified	Uncertain significance (Nov 17, 2022)
16-58709490-C-A		Early infantile epileptic encephalopathy with suppression bursts • Developmental and epileptic encephalopathy, 82	Likely pathogenic (May 29, 2020)
16-58709497-T-C			Benign (Jul 17, 2023)
16-58709503-G-A		Developmental and epileptic encephalopathy, 82	Uncertain significance (May 03, 2023)
16-58709505-T-C			Uncertain significance (Oct 12, 2021)
16-58709518-G-C		GOT2-related disorder	Conflicting classifications of pathogenicity (Jan 01, 2024)
16-58709538-C-T		not specified	Uncertain significance (Jul 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GOT2	protein_coding	protein_coding	ENST00000245206	10	27227

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0142	0.985	125733	0	13	125746	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	190	252	0.754	0.0000144	2808
Missense in Polyphen		41	70.613	0.58063		846
Synonymous	1.93	68	91.5	0.743	0.00000523	846
Loss of Function	2.84	7	21.1	0.332	9.78e-7	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000208
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000541	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the irreversible transamination of the L- tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Plays a key role in amino acid metabolism. Important for metabolite exchange between mitochondria and cytosol. Facilitates cellular uptake of long-chain free fatty acids. {ECO:0000269|PubMed:9537447}.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Arginine and proline metabolism - Homo sapiens (human);Phenylalanine metabolism - Homo sapiens (human);Fat digestion and absorption - Homo sapiens (human);Phenylalanine, tyrosine and tryptophan biosynthesis - Homo sapiens (human);Cysteine and methionine metabolism - Homo sapiens (human);Tyrosine metabolism - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Argininemia;2-Hydroxyglutric Aciduria (D And L Form);Citrullinemia Type I;Carbamoyl Phosphate Synthetase Deficiency;Argininosuccinic Aciduria;Malate-Aspartate Shuttle;Urea Cycle;Glutaminolysis and Cancer;Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;Ornithine Transcarbamylase Deficiency (OTC Deficiency);4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;Alanine and aspartate metabolism;Amino Acid metabolism;Glycolysis and Gluconeogenesis;Metabolism of carbohydrates;Alanine Aspartate Asparagine metabolism;Degradation of cysteine and homocysteine;Metabolism of amino acids and derivatives;malate-aspartate shuttle;Glycine Serine metabolism;Tyrosine metabolism;Metabolism;Methionine Cysteine metabolism;Phenylalanine degradation;L-kynurenine degradation;4-hydroxyproline degradation;Methionine and cysteine metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Glyoxylate metabolism and glycine degradation;Arginine Proline metabolism;Gluconeogenesis;Glucose metabolism;Sulfur amino acid metabolism;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.975

Intolerance Scores

• loftool: 0.107
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.231
• hipred: Y
• hipred_score: 0.794
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.370

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Got2

Gene ontology

• Biological process: gluconeogenesis;2-oxoglutarate metabolic process;oxaloacetate metabolic process;aspartate metabolic process;aspartate biosynthetic process;aspartate catabolic process;glutamate metabolic process;female pregnancy;lactation;cellular amino acid biosynthetic process;response to muscle activity;fatty acid transport;4-hydroxyproline catabolic process;glutamate catabolic process to aspartate;glutamate catabolic process to 2-oxoglutarate;response to insulin;response to morphine;response to ethanol;glyoxylate metabolic process;L-kynurenine metabolic process
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial matrix;plasma membrane;cell surface;T-tubule;protein-containing complex;perikaryon;myelin sheath;extracellular exosome
• Molecular function: RNA binding;L-aspartate:2-oxoglutarate aminotransferase activity;phospholipid binding;kynurenine-oxoglutarate transaminase activity;amino acid binding;enzyme binding;pyridoxal phosphate binding;protein homodimerization activity;4-hydroxyglutamate transaminase activity