GOT2

glutamic-oxaloacetic transaminase 2

Basic information

Region (hg38): 16:58707131-58734342

Links

ENSG00000125166NCBI:2806OMIM:138150HGNC:4433Uniprot:P00505AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Developmental and epileptic encephalopathy 82ARNeurologicThe 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 progressBiochemical; Neurologic31422819

ClinVar

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

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
clinvar
11
clinvar
8
clinvar
20
missense
3
clinvar
46
clinvar
3
clinvar
6
clinvar
58
nonsense
0
start loss
0
frameshift
1
clinvar
1
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
splice region
1
3
2
6
non coding
15
clinvar
4
clinvar
19
Total 0 4 48 29 18

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)3021253
16-58708208-C-T Developmental and epileptic encephalopathy, 82 Uncertain significance (Mar 18, 2021)2441781
16-58708213-G-A Likely benign (Dec 11, 2023)2176327
16-58708216-G-A Benign (Jan 08, 2024)733891
16-58708220-G-C not specified Uncertain significance (Jun 13, 2023)2560162
16-58708225-G-A Likely benign (Feb 21, 2023)2792175
16-58708250-T-C Uncertain significance (Nov 15, 2022)2029681
16-58708284-G-A Likely benign (Oct 27, 2023)1566877
16-58708286-C-T Likely benign (Oct 03, 2023)747258
16-58708287-G-A Likely benign (Jun 08, 2021)1640898
16-58708301-G-C Benign (Nov 02, 2023)734481
16-58708308-G-T Likely benign (Feb 18, 2023)2981014
16-58708310-A-C Likely benign (Jul 25, 2023)2743771
16-58709407-A-C Likely benign (Jun 21, 2023)2876494
16-58709417-C-T Uncertain significance (Oct 24, 2022)1935868
16-58709436-G-A Uncertain significance (Dec 09, 2021)1961271
16-58709456-T-G not specified Uncertain significance (May 23, 2024)3281991
16-58709461-C-T Uncertain significance (Jun 18, 2022)2189369
16-58709462-G-A Benign (Jan 22, 2024)1614801
16-58709472-T-C not specified Uncertain significance (Nov 17, 2022)1419631
16-58709490-C-A Early infantile epileptic encephalopathy with suppression bursts • Developmental and epileptic encephalopathy, 82 Likely pathogenic (May 29, 2020)691281
16-58709497-T-C Benign (Jul 17, 2023)2064625
16-58709503-G-A Developmental and epileptic encephalopathy, 82 Uncertain significance (May 03, 2023)2570661
16-58709505-T-C Uncertain significance (Oct 12, 2021)1393222
16-58709518-G-C GOT2-related disorder Conflicting classifications of pathogenicity (Jan 01, 2024)2080831

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
GOT2protein_codingprotein_codingENST00000245206 1027227
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.01420.9851257330131257460.0000517
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.391902520.7540.00001442808
Missense in Polyphen4170.6130.58063846
Synonymous1.936891.50.7430.00000523846
Loss of Function2.84721.10.3329.78e-7243

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002110.000208
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.0001390.000139
European (Non-Finnish)0.00005410.0000527
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Got2
Phenotype

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