GOT2

Summary

GOT2 (glutamic-oxaloacetic transaminase 2, HGNC:4433) is a protein-coding gene on chromosome 16q21, encoding Aspartate aminotransferase, mitochondrial (P00505). Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). It is a selective cancer dependency (DepMap: 11.1% of cell lines).

Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles. The two enzymes are homodimeric and show close homology. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2806 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 82 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 161 total — 4 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 11.1% of screened cell lines
• MANE Select transcript: NM_002080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4433
Approved symbol	GOT2
Name	glutamic-oxaloacetic transaminase 2
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	mitAAT, KATIV, KAT4, KYAT4, mAspAT
Ensembl gene	ENSG00000125166
Ensembl biotype	protein_coding
OMIM	138150
Entrez	2806

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000245206, ENST00000434819, ENST00000492378, ENST00000494627, ENST00000496461, ENST00000564400, ENST00000568368, ENST00000857877, ENST00000857878, ENST00000857879, ENST00000857880, ENST00000857881, ENST00000857882, ENST00000857883, ENST00000857884, ENST00000916496, ENST00000916497, ENST00000916498, ENST00000916499, ENST00000954609, ENST00000954610, ENST00000954611, ENST00000954612

RefSeq mRNA: 2 — MANE Select: NM_002080 NM_001286220, NM_002080

CCDS: CCDS10801, CCDS67045

Canonical transcript exons

ENST00000245206 — 10 exons

Exon	Start	End
ENSE00001671155	58716663	58716813
ENSE00001773713	58734140	58734316
ENSE00001776353	58716014	58716179
ENSE00001785064	58709417	58709567
ENSE00001897591	58707131	58708293
ENSE00003526864	58718527	58718688
ENSE00003531906	58723746	58723902
ENSE00003534318	58722150	58722278
ENSE00003565077	58718196	58718300
ENSE00003597918	58719196	58719255

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 85.1048 / max 614.4276, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157633	82.9052	1819
157632	1.6042	796
157631	0.5954	364

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.97	gold quality
left ventricle myocardium	UBERON:0006566	98.85	gold quality
heart left ventricle	UBERON:0002084	98.73	gold quality
cardiac ventricle	UBERON:0002082	98.72	gold quality
heart right ventricle	UBERON:0002080	98.69	gold quality
gastrocnemius	UBERON:0001388	98.66	gold quality
triceps brachii	UBERON:0001509	98.66	gold quality
apex of heart	UBERON:0002098	98.65	gold quality
vastus lateralis	UBERON:0001379	98.62	gold quality
middle temporal gyrus	UBERON:0002771	98.55	gold quality
quadriceps femoris	UBERON:0001377	98.52	gold quality
right atrium auricular region	UBERON:0006631	98.30	gold quality
muscle organ	UBERON:0001630	98.29	gold quality
skeletal muscle organ	UBERON:0014892	98.29	gold quality
muscle of leg	UBERON:0001383	98.27	gold quality
cardiac atrium	UBERON:0002081	98.20	gold quality
gluteal muscle	UBERON:0002000	98.13	gold quality
diaphragm	UBERON:0001103	98.06	gold quality
skeletal muscle tissue	UBERON:0001134	98.04	gold quality
biceps brachii	UBERON:0001507	97.99	gold quality
right lobe of liver	UBERON:0001114	97.85	gold quality
pigmented layer of retina	UBERON:0001782	97.82	gold quality
deltoid	UBERON:0001476	97.81	gold quality
frontal pole	UBERON:0002795	97.81	gold quality
retina	UBERON:0000966	97.79	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.77	gold quality
myocardium	UBERON:0002349	97.70	gold quality
muscle tissue	UBERON:0002385	97.61	gold quality
heart	UBERON:0000948	97.59	gold quality
body of tongue	UBERON:0011876	97.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	12.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SREBF1

miRNA regulators (miRDB)

68 targeting GOT2, 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-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-105-5P	99.54	69.24	2060

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• Frequency of polymorphism are similar in control groups and schizophrenics. (PMID:17728674)
• PTLP activity is positively associated with serum ALT1, GOT1 and GOT2 in type 2 diabetes mellitus and metabolic syndrome. (PMID:17877759)
• The lipid binding process in L-FABP is associated with backbone dynamics. (PMID:22713574)
• High glucose infusion was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm). (PMID:24937540)
• A previously unknown mechanism by which GOT2 acetylation stimulates the malate-aspartate NADH shuttle activity and oxidative protection. (PMID:25755250)
• Data suggest that, in context of abnormal hepatic lipid accumulation in nonalcoholic fatty liver disease, circulating GOT2 rises due to up-regulation of hepatic expression of GOT2 associated with greater gluconeogenesis and insulin resistance. (PMID:26791191)
• Like in adults, FABP seems to be associated with markers of metabolic risk in obese adolescents (PMID:28183455)
• The results of our study on this larger than 5800-patient cohort suggest beneficial effects of high B12 vitamin level, negative effects of high sodium levels or high AST (aspartate aminotransferase) liver enzyme levels to cognition. (PMID:28918286)
• Study utilizing integrative analysis of transcriptomic, metabolomic, and clinical data propose a model of GOT2 transcriptional regulation, in which the cooperative phosphorylation of STAT3 and direct joint binding of STAT3 and p65/NF-kappaB to the proximal GOT2 promoter are important. Furthermore, high aberrant GOT2 expression is prognostic in diffuse large B-cell lymphoma. (PMID:29666362)
• BRCA1 forms a co-repressor complex with ZBRK1 that coordinately represses GOT2 expression via a ZBRK1 recognition element in the promoter of GOT2. (PMID:30714292)
• Polymorphisms of rs7204324 on GOT2 may play an important role in susceptibility to liver injury following exposure to N,N-dimethylformamide . (PMID:30993423)
• data provide a mechanistic basis for the biochemical abnormalities in GOT2 deficiency that may also hold for other MAS defects (PMID:31422819)
• High circ-SEC31A expression predicts unfavorable prognoses in non-small cell lung cancer by regulating the miR-520a-5p/GOT-2 axis. (PMID:32499446)
• Circular RNA circ_0003028 contributes to tumorigenesis by regulating GOT2 via miR-1298-5p in non-small cell lung cancer. (PMID:34077306)
• GOT2 Silencing Promotes Reprogramming of Glutamine Metabolism and Sensitizes Hepatocellular Carcinoma to Glutaminase Inhibitors. (PMID:35895805)
• Low expression of GOT2 promotes tumor progress and predicts poor prognosis in hepatocellular carcinoma. (PMID:38095985)
• Surgical resection of lung cancer inhibits mRNA expression of GOT2 gene encoding kynurenine aminotransferase in leukocytes. (PMID:38153082)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	got2b	ENSDARG00000005840
danio_rerio	got2a	ENSDARG00000041068
mus_musculus	Got2	ENSMUSG00000031672
rattus_norvegicus	Got2	ENSRNOG00000011782
rattus_norvegicus	Got2-ps6	ENSRNOG00000057091
rattus_norvegicus		ENSRNOG00000064101
drosophila_melanogaster	Got2	FBGN0001125
caenorhabditis_elegans		WBGENE00015778
caenorhabditis_elegans	got-2.1	WBGENE00016652

Paralogs (2): GOT1 (ENSG00000120053), GOT1L1 (ENSG00000169154)

Protein

Protein identifiers

Aspartate aminotransferase, mitochondrial — P00505 (reviewed: P00505)

Alternative names: Fatty acid-binding protein, Glutamate oxaloacetate transaminase 2, Kynurenine aminotransferase 4, Kynurenine aminotransferase IV, Kynurenine–oxoglutarate transaminase 4, Kynurenine–oxoglutarate transaminase IV, Plasma membrane-associated fatty acid-binding protein, Transaminase A

All UniProt accessions (2): P00505, H3BRE7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion matrix. Cell membrane.

Disease relevance. Developmental and epileptic encephalopathy 82 (DEE82) [MIM:618721] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE82 is an autosomal recessive metabolic encephalopathy characterized by epilepsy from the first year of life, global developmental delay, hypotonia and feeding difficulties apparent soon after birth, and intellectual and motor disabilities. Other features include poor overall growth, progressive microcephaly and biochemical abnormalities, including increased serum lactate and ammonia. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by long-time exposure to alcohol.

Miscellaneous. In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P00505-1	1	yes
P00505-2	2

RefSeq proteins (2): NP_001273149, NP_002071* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000796	Asp_trans	Family
IPR004838	NHTrfase_class1_PyrdxlP-BS	Binding_site
IPR004839	Aminotransferase_I/II_large	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily

Pfam: PF00155

Enzyme classification (BRENDA):

• EC 2.6.1.1 — aspartate transaminase (BRENDA: 87 organisms, 168 substrates, 157 inhibitors, 242 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-ASPARTATE	0.039–37	67
2-OXOGLUTARATE	0.007–6.9	66
OXALOACETATE	0.01–2.45	32
L-GLUTAMATE	0.5–37	31
L-PHENYLALANINE	1.1–6.6	3
L-TRYPTOPHAN	2.3–5	3
L-TYROSINE	1.43–1.6	3
2-METHOXYPHENYLPYRUVATE	5.84–12.07	2
2-OXO-4-PHENYL-BUTANOIC ACID	0.77–0.86	2
3,4-DIMETHOXYPHENYLPYRUVATE	1.01–10.32	2
3-METHOXYPHENYLPYRUVATE	4.92–11.56	2
4-METHOXYPHENYLPYRUVATE	4.12–10.14	2
L-2-AMINO-4-METHOXY-4-OXOBUTANOIC ACID	4.1–20.3	2
L-ALANINE	3.5–140	2
L-CYSTEINE	8.57–20.62	2

Catalyzed reactions (Rhea), 2 shown:

• L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate (RHEA:21824)
• L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + H2O (RHEA:65560)

UniProt features (94 total): modified residue 40, helix 17, strand 11, sequence variant 8, turn 7, binding site 4, sequence conflict 4, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9YB6	X-RAY DIFFRACTION	1.5
5AX8	X-RAY DIFFRACTION	2.99
8SKR	ELECTRON MICROSCOPY	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00505-F1	94.77	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 (4): 65; 162; 215; 407

Post-translational modifications (40): 82, 90, 90, 96, 96, 107, 107, 122, 122, 143, 159, 159, 185, 185, 227, 234, 279, 279, 296, 296 …

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1614558	Degradation of cysteine and homocysteine
R-HSA-389661	Glyoxylate metabolism and glycine degradation
R-HSA-8963693	Aspartate and asparagine metabolism
R-HSA-8964539	Glutamate and glutamine metabolism
R-HSA-9856872	Malate-aspartate shuttle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-611105	Respiratory electron transport
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 316 (showing top): MORF_DNMT1, GOBP_RESPONSE_TO_ETHANOL, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, MORF_ESPL1, MORF_BUB1, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, MORF_RRM1, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, MORF_HDAC2

GO Biological Process (15): 2-oxoglutarate metabolic process (GO:0006103), oxaloacetate metabolic process (GO:0006107), aspartate metabolic process (GO:0006531), L-aspartate biosynthetic process (GO:0006532), L-aspartate catabolic process (GO:0006533), glutamate metabolic process (GO:0006536), fatty acid transport (GO:0015908), trans-4-hydroxy-L-proline catabolic process (GO:0019470), obsolete L-glutamate catabolic process to aspartate (GO:0019550), malate-aspartate shuttle (GO:0043490), response to ethanol (GO:0045471), amino acid metabolic process (GO:0006520), L-glutamate catabolic process (GO:0006538), lipid transport (GO:0006869), biosynthetic process (GO:0009058)

GO Molecular Function (7): RNA binding (GO:0003723), L-aspartate:2-oxoglutarate transaminase activity (GO:0004069), L-kynurenine:2-oxoglutarate transaminase activity (GO:0016212), pyridoxal phosphate binding (GO:0030170), catalytic activity (GO:0003824), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	4
Metabolism	2
Sulfur amino acid metabolism	1
Respiratory electron transport	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dicarboxylic acid metabolic process	4
L-amino acid catabolic process	3
amino acid metabolic process	2
aspartate metabolic process	2
dicarboxylic acid catabolic process	2
proteinogenic amino acid catabolic process	2
aspartate family amino acid biosynthetic process	1
dicarboxylic acid biosynthetic process	1
lipid transport	1
monocarboxylic acid transport	1
modified amino acid catabolic process	1
non-proteinogenic amino acid catabolic process	1
L-aspartate:2-oxoglutarate transaminase activity	1
NAD+ metabolic process	1
L-malate dehydrogenase (NAD+) activity	1
mitochondrial transmembrane transport	1
response to alcohol	1
primary metabolic process	1
glutamate metabolic process	1
transport	1
lipid localization	1
metabolic process	1
nucleic acid binding	1
amino acid transaminase activity	1
transaminase activity	1
anion binding	1
vitamin B6 binding	1
molecular_function	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

4140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GOT2	FABP1	P07148	957
GOT2	FABP2	P12104	955
GOT2	FABP3	P05413	946
GOT2	ACOD1	A6NK06	924
GOT2	MDH2	P40926	902
GOT2	FABP4	P15090	897
GOT2	FABP5	Q01469	888
GOT2	CD36	P16671	859
GOT2	SCARB1	Q8WTV0	831
GOT2	TAT	P17735	814
GOT2	FABP6	P51161	810
GOT2	SCARB2	Q14108	795
GOT2	PPARG	P37231	793
GOT2	ALB	P02768	781
GOT2	PPARA	Q07869	778

IntAct

70 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
Bles03		psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
GOT2	APCS	psi-mi:“MI:0915”(physical association)	0.370
GOT2	CCL21	psi-mi:“MI:0915”(physical association)	0.370
GAPDH	GOT2	psi-mi:“MI:0915”(physical association)	0.370
GLRX	GOT2	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PHOSPHO1	DDX39A	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
DAG1	AGRN	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
SPRYD4	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
SHOC2	PNP	psi-mi:“MI:0914”(association)	0.350
ZMYND11	GOT2	psi-mi:“MI:0914”(association)	0.350
MAP3K7	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAP2K2	IPO5	psi-mi:“MI:0914”(association)	0.350
RIPK4	TBCA	psi-mi:“MI:0914”(association)	0.350
PRKCZ	PGRMC1	psi-mi:“MI:0914”(association)	0.350
MYLK	ACOT7	psi-mi:“MI:0914”(association)	0.350
PRKD2	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CEP135	WDR91	psi-mi:“MI:0914”(association)	0.350

BioGRID (147): GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), CCBL2 (Co-fractionation), FAH (Co-fractionation), GOT2 (Co-fractionation), GPI (Co-fractionation), GYG1 (Co-fractionation), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS), GOT2 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9J4, B3FHT4, C9K7C8, F1QCN0, O04015, O04226, O13750, O65361, P00505, P00506, P00507, P00508, P05202, P0ABU5, P0ABU6, P0DPI2, P12344, P12345, P13803, P13804, P28734, P32449, P37833, P41758, P53596, P54887, P54888, P55880, P56571, P68209, Q16MW6, Q28F67, Q29554, Q2KJE4, Q46948, Q4R559, Q5RC31, Q5REB0, Q61941, Q64428

Diamond homologs: A0A0C1E1D0, A5A6K8, O42652, O85746, O94320, P00503, P00504, P00505, P00506, P00507, P00508, P00509, P04693, P05201, P05202, P08906, P08907, P12344, P12345, P13221, P17174, P23542, P26563, P28011, P28734, P33097, P37833, P43336, P44425, P46248, P46643, P46644, P46645, P46646, P58661, P72173, P74861, P95468, Q01802, Q02636

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
GOT2	“up-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
GOT2	“down-regulates quantity”	“glutamic acid”	“chemical modification”
GOT2	“up-regulates quantity”	L-aspartate(1-)	“chemical modification”
GOT2	“up-regulates quantity”	oxaloacetate(2-)	“chemical modification”
GOT2	“up-regulates quantity”	L-glutamate(1-)	“chemical modification”
GOT2	“down-regulates quantity”	oxaloacetate(2-)	“chemical modification”
GOT2	“down-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
GOT2	“down-regulates quantity”	L-glutamate(1-)	“chemical modification”
GOT2	“down-regulates quantity”	L-aspartate(1-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	77
Likely benign	48
Benign	20

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
691278	NM_002080.4(GOT2):c.618TCT[2] (p.Leu209del)	Likely pathogenic
691279	NM_002080.4(GOT2):c.1009C>G (p.Arg337Gly)	Likely pathogenic
691280	NM_002080.4(GOT2):c.784C>G (p.Arg262Gly)	Likely pathogenic
691281	NM_002080.4(GOT2):c.1097G>T (p.Gly366Val)	Likely pathogenic

SpliceAI

1159 predictions. Top by Δscore:

Variant	Effect	Δscore
16:58708290:CCAC:C	acceptor_gain	1.0000
16:58708291:CAC:C	acceptor_gain	1.0000
16:58708291:CACC:C	acceptor_gain	1.0000
16:58708292:ACC:A	acceptor_loss	1.0000
16:58708294:C:CC	acceptor_gain	1.0000
16:58708294:CTGC:C	acceptor_loss	1.0000
16:58708295:T:G	acceptor_loss	1.0000
16:58709412:CTCA:C	donor_loss	1.0000
16:58709413:TCAC:T	donor_loss	1.0000
16:58709414:CAC:C	donor_loss	1.0000
16:58709415:A:AC	donor_gain	1.0000
16:58709415:ACCTG:A	donor_loss	1.0000
16:58709416:C:CC	donor_gain	1.0000
16:58716656:AGCTT:A	donor_loss	1.0000
16:58716657:GCTTA:G	donor_loss	1.0000
16:58716658:CTTAC:C	donor_loss	1.0000
16:58716659:TTACC:T	donor_loss	1.0000
16:58716660:T:TG	donor_loss	1.0000
16:58716661:ACCA:A	donor_loss	1.0000
16:58716662:C:CT	donor_loss	1.0000
16:58716709:AATGC:A	donor_gain	1.0000
16:58716784:CA:C	acceptor_gain	1.0000
16:58716809:CTTTT:C	acceptor_gain	1.0000
16:58716811:TTT:T	acceptor_gain	1.0000
16:58716812:TT:T	acceptor_gain	1.0000
16:58716813:TC:T	acceptor_loss	1.0000
16:58716814:C:A	acceptor_loss	1.0000
16:58716814:C:CC	acceptor_gain	1.0000
16:58719191:CTCA:C	donor_loss	1.0000
16:58719192:T:TA	donor_loss	1.0000

AlphaMissense

2829 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:58709444:G:C	F381L	1.000
16:58709444:G:T	F381L	1.000
16:58709446:A:G	F381L	1.000
16:58716679:C:A	K279N	1.000
16:58716679:C:G	K279N	1.000
16:58716680:T:A	K279M	1.000
16:58716788:T:A	D243V	1.000
16:58716788:T:G	D243A	1.000
16:58718253:A:C	N215K	1.000
16:58718253:A:T	N215K	1.000
16:58718640:A:G	W162R	1.000
16:58718640:A:T	W162R	1.000
16:58722239:A:G	Y96H	1.000
16:58708244:C:G	R407P	0.999
16:58709445:A:C	F381C	0.999
16:58709445:A:G	F381S	0.999
16:58709446:A:C	F381V	0.999
16:58709446:A:T	F381I	0.999
16:58709448:A:G	M380T	0.999
16:58709451:C:T	G379D	0.999
16:58709538:C:G	R350P	0.999
16:58716015:A:G	W340R	0.999
16:58716015:A:T	W340R	0.999
16:58716065:C:T	G323E	0.999
16:58716066:C:A	G323W	0.999
16:58716079:G:C	N318K	0.999
16:58716079:G:T	N318K	0.999
16:58716083:G:A	S317F	0.999
16:58716096:G:T	R313S	0.999
16:58716167:C:T	G289E	0.999

dbSNP variants (sampled 300 via entrez): RS1000116019 (16:58716379 T>A), RS1000270956 (16:58712426 G>A), RS1000495685 (16:58735917 A>G), RS1000522007 (16:58725182 T>C), RS1000582946 (16:58731334 G>A), RS1000617808 (16:58718918 G>A), RS1000770631 (16:58719332 C>T), RS1000998764 (16:58725518 T>A), RS1001032279 (16:58731150 T>A,C), RS1001187016 (16:58714071 A>C), RS1001581436 (16:58732851 T>C), RS1001609534 (16:58718868 G>A), RS1001923029 (16:58726467 A>G), RS1002030142 (16:58731568 A>G), RS1002093230 (16:58725005 C>A,T)

Disease associations

OMIM: gene MIM:138150 | disease phenotypes: MIM:618721

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 82	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (2): developmental and epileptic encephalopathy, 82 (MONDO:0032880), developmental and epileptic encephalopathy (MONDO:0100620)

Orphanet (0):

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000253	Progressive microcephaly
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001319	Neonatal hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001344	Absent speech
HP:0001987	Hyperammonemia
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002151	Increased circulating lactate concentration
HP:0002313	Spastic paraparesis
HP:0002510	Spastic tetraplegia
HP:0002540	Inability to walk
HP:0002719	Recurrent infections
HP:0004322	Short stature
HP:0004325	Decreased body weight
HP:0008872	Feeding difficulties in infancy
HP:0010864	Severe intellectual disability

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000363_9	QT interval	3.000000e-25
GCST000943_2	Aortic root size	3.000000e-06
GCST005999_22	Aspartate aminotransferase levels	2.000000e-12
GCST006616_6	Uterine fibroid number (single vs multiple)	1.000000e-06
GCST007329_22	Automobile speeding propensity	2.000000e-08
GCST007627_3	Impulsivity (attentional)	6.000000e-07
GCST009391_1343	Metabolite levels	6.000000e-06
GCST009391_1379	Metabolite levels	2.000000e-07
GCST009391_1388	Metabolite levels	5.000000e-06
GCST009391_1697	Metabolite levels	5.000000e-06
GCST009391_518	Metabolite levels	4.000000e-06
GCST009733_25	Urinary metabolite levels in chronic kidney disease	3.000000e-19
GCST010244_353	Triglyceride levels	4.000000e-08
GCST011348_39	High density lipoprotein cholesterol levels	3.000000e-17
GCST011351_20	Aspartate aminotransferase levels	3.000000e-12
GCST012020_466	Serum metabolite levels	8.000000e-42
GCST012020_467	Serum metabolite levels	8.000000e-27
GCST90011899_26	Aspartate aminotransferase levels	9.000000e-41

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004736	aspartate aminotransferase measurement
EFO:0009410	uterine fibroid measurement
EFO:0008579	risk-taking behaviour
EFO:0006946	behavioural disinhibition measurement
EFO:0010362	lysophosphatidylcholine 20:3 measurement
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement
EFO:0010344	cholesteryl ester 18:1 measurement
EFO:0010117	pyruvate measurement
EFO:0005116	urinary metabolite measurement
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4524033 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs14221	GOT2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects methylation, decreases expression, increases expression, affects expression	4
bisphenol A	affects cotreatment, affects methylation, decreases expression, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, affects methylation, increases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	affects cotreatment, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4731068	Binding	Inhibition of aspartate aminotransferase (unknown origin) up to 10 mM by SSDH coupled enzyme based UV-Vis spectrophotometry	Mechanism-Based Design of 3-Amino-4-Halocyclopentenecarboxylic Acids as Inactivators of GABA Aminotransferase. — ACS Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3NG	HEK293 GOT2 KO clone A3	Transformed cell line	Female
CVCL_C3NH	HEK293 GOT2 KO clone A6	Transformed cell line	Female
CVCL_C3NI	HEK293 GOT2 KO clone A7	Transformed cell line	Female
CVCL_E1YC	HAP1 GOT2 (-) 2	Cancer cell line	Male
CVCL_XP31	HAP1 GOT2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).