GOT1

Summary

GOT1 (glutamic-oxaloacetic transaminase 1, HGNC:4432) is a protein-coding gene on chromosome 10q24.2, encoding Aspartate aminotransferase, cytoplasmic (P17174). Biosynthesis of L-glutamate from L-aspartate or L-cysteine.

Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and 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.

Source: NCBI Gene 2805 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 67 total — 1 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4432
Approved symbol	GOT1
Name	glutamic-oxaloacetic transaminase 1
Location	10q24.2
Locus type	gene with protein product
Status	Approved
Aliases	AST1, SGOT, AST
Ensembl gene	ENSG00000120053
Ensembl biotype	protein_coding
OMIM	138180
Entrez	2805

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370508, ENST00000471741, ENST00000489349, ENST00000894926, ENST00000894927, ENST00000894928, ENST00000923596, ENST00000923597, ENST00000923598, ENST00000955163

RefSeq mRNA: 1 — MANE Select: NM_002079 NM_002079

CCDS: CCDS7479

Canonical transcript exons

ENST00000370508 — 9 exons

Exon	Start	End
ENSE00000719391	99403469	99403634
ENSE00000719422	99405756	99405860
ENSE00000719436	99406137	99406249
ENSE00000719450	99406726	99406849
ENSE00000719466	99420624	99420805
ENSE00000811273	99403724	99403874
ENSE00001452885	99396870	99397686
ENSE00001870868	99430448	99430624
ENSE00003473178	99402580	99402722

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.5659 / max 405.6887, expressed in 1806 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110984	33.4686	1799
110985	1.0927	731
110986	0.9829	643
110987	0.0218	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.54	gold quality
left ventricle myocardium	UBERON:0006566	99.52	gold quality
apex of heart	UBERON:0002098	99.14	gold quality
myocardium	UBERON:0002349	99.13	gold quality
cardiac ventricle	UBERON:0002082	99.06	gold quality
heart left ventricle	UBERON:0002084	99.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.93	gold quality
body of tongue	UBERON:0011876	98.93	gold quality
cardiac atrium	UBERON:0002081	98.88	gold quality
right atrium auricular region	UBERON:0006631	98.87	gold quality
vastus lateralis	UBERON:0001379	98.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.67	gold quality
prefrontal cortex	UBERON:0000451	98.59	gold quality
diaphragm	UBERON:0001103	98.59	gold quality
biceps brachii	UBERON:0001507	98.57	gold quality
quadriceps femoris	UBERON:0001377	98.55	gold quality
pons	UBERON:0000988	98.54	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.54	gold quality
gastrocnemius	UBERON:0001388	98.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.47	gold quality
right lobe of liver	UBERON:0001114	98.45	gold quality
skeletal muscle tissue	UBERON:0001134	98.42	gold quality
triceps brachii	UBERON:0001509	98.40	gold quality
muscle organ	UBERON:0001630	98.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.03	gold quality
right frontal lobe	UBERON:0002810	98.01	gold quality
liver	UBERON:0002107	98.00	gold quality
muscle of leg	UBERON:0001383	97.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	98.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPB, MSC, NFIA, NR3C1, PPARA, PPARG, RORA, RXRA, TP53

miRNA regulators (miRDB)

45 targeting GOT1, 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-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-7845-5P	99.88	64.88	771
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4763-3P	99.10	67.83	2649

Literature-anchored findings (GeneRIF, showing 40)

• Glucose intolerance is associated with elevated serum aminotransferase independent of obesity. (PMID:12480555)
• mildly elevated in severe acute respiratory syndrome patients during second week after onset of fever. (PMID:15306699)
• saliva AST and ALP may have roles in development of periodontal diseases (PMID:16681433)
• PTLP activity is positively associated with serum ALT1, GOT1 and GOT2 in type 2 diabetes mellitus and metabolic syndrome. (PMID:17877759)
• Abnormal serum aminotransferase values are uncommon in severely obese children in France. (PMID:17907318)
• Data revealed higher aspartate aminotransferase for women with a family history of diabetes, when adjusted for age and BMI. (PMID:18242760)
• Serum bilirubin, alkaline phosphatase, and aspartate aminotransferase are an efficient set of biochemistries to identify UDCA-treated patients with primary biliary cirrhosis at risk of death or liver transplantation (LT). (PMID:18752324)
• Neither ALT nor GGT concentrations were correlated with ALP concentration, but AST concentration was moderately correlated with ALP concentration. (PMID:19012630)
• Results suggest that alanine and aspartate aminotransferase levels and AST/ALT ratio do not seem to be reliable predictors for non-alcoholic steatohepatitis. (PMID:19370784)
• the management of patients with pyelonephritis should take into account that moderate and self-limited abnormalities in aminotransferase levels are frequent during the acute phase of the disease (PMID:19393479)
• The association of coffee and green tea consumption with serum activities of liver enzymes in free-living Japanese men and women was examined, focusing on sex difference and effect modifications of alcohol and obesity. (PMID:20205615)
• Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency. (PMID:20499337)
• liver enzymes, including AST, were significantly associated with IR according to direct clamp assessment, which were independent of the traditional risk factors in diabetic patients (PMID:20972737)
• Data indicate that the percentages of CD4(+)CXCR5(+) TFH in IA patients were positively correlated with AST. (PMID:21750724)
• we discovered a rare in-frame deletion in GOT1 gene, which inactivates cAST enzyme in the Old Order Amish. (PMID:21900944)
• The patterns of interaction between smoking and alcohol consumption or BMI with respect to AST and ALT resembled those observed for gamma-GT. (PMID:22132177)
• This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths. (PMID:22242166)
• APRI and AST/ALT are independent predictors for significant fibrosis in chronic hepatitis C patients. (PMID:22352690)
• Alcohol consumption, smoking status, and metabolic syndrome impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), was determined. (PMID:23667618)
• Significantly higher GOT levels were found in the 1-20 year age group of type 1 (PMID:24849491)
• The aim of this study was to establish the reference intervals (RIs) of total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate transaminase (AST), and creatinine (CREA) for apparently healthy elderly (Han ethnicity) in Shuyang, China. (PMID:25272068)
• We propose the GOT1 expression status as a simple and reliable prognostic biomarker in pancreatic ductal adenocarcinoma (PMID:25595905)
• Human GOT1 was expressed in E coli, purified by affinity chromatography and preliminary crystallographic studies were done. (PMID:26003525)
• The serum hepcidin, ferritin, alanine transaminase, aspartate transaminase, gamma-glutamyltransferase and bilirubin were examined in two independent Chinese cohorts consisted of 3455 individuals. (PMID:26290281)
• High AST1 expression is associated with high mortality in hemodialysis patients. (PMID:26333544)
• Data suggest that, in context of abnormal hepatic lipid accumulation in nonalcoholic fatty liver disease, circulating GOT1 rises due to up-regulation of hepatic expression of GOT1 associated with greater gluconeogenesis and insulin resistance. (PMID:26791191)
• Elevated aspartate aminotransferase level was associated with hepatocellular carcinoma. (PMID:26881519)
• Elevated levels of ALT are Associated with Cardiovascular disease. (PMID:27872510)
• Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection (PMID:28351330)
• Early abnormal liver enzyme levels of aspartate aminotransferase and alanine aminotransferase may increase the prevalence of human cytomegalovirus antigenemia after hematopoietic stem cell transplantation. (PMID:28415934)
• GOT1 plays an important role in energy metabolism and ROS balance in chronic acidosis stress in pancreatic tumor cells. (PMID:28455244)
• HIF-2a regulates non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway and GOT1 expression in human pancreatic ductal adenocarcinoma. (PMID:28544376)
• ALT is a more suitable index than AST for developing a regression model. (PMID:28628604)
• Missense variant (p.Gln208Glu, rs374966349) in glutamate oxaloacetate transaminase 1 (GOT1) was found, as a putative causal variant predisposing to Familial Macro-aspartate aminotransferase . (PMID:28716744)
• high transaminase elevations do not predict severe complications or reflect remnant ischemic area. (PMID:29553104)
• Study suggests an important role of GOT1 to coordinate the glycolytic and the oxidative phosphorylation pathways in KRAS mutated cancer cells. High levels of GOT1 were further linked to poor survival as analysed by the GEPIA web tool, in thyroid and breast carcinoma and in lung adenocarcinoma. (PMID:29751795)
• findings demonstrate that miR-9 regulates ferroptosis by targeting GOT1 in melanoma cells, illustrating the important role of miRNA in ferroptosis. (PMID:30035324)
• we assessed the stability of pyridoxal 5’-phosphate (PLP) bound to hGOT1 for the three variant and wildtype (WT) proteins. Conformational transition was associated with the rearrangement of the P15-R32 small domain loop providing substrate access to the R387/R293 binding motif. The amino acid substitutions at positions 266, 267, and 300 reduced the structural correlation between PLP and the protein active site (PMID:30208107)
• Association between serum liver enzymes and all-cause mortality: The Japan Public Health Center-based Prospective Study. (PMID:30566759)
• This study suggested that miR-9-5p regulates GOT1 expression in pancreatic cancer, thereby stunting proliferation, invasion, glutamine metabolism and redox homeostasis, and that miR-9-5p may serve as a prognostic or therapeutic target for pancreatic cancer. (PMID:30591220)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	got1	ENSDARG00000039093
mus_musculus	Got1	ENSMUSG00000025190
rattus_norvegicus	Got1	ENSRNOG00000016356
drosophila_melanogaster	Got1	FBGN0001124
caenorhabditis_elegans		WBGENE00020146

Paralogs (2): GOT2 (ENSG00000125166), GOT1L1 (ENSG00000169154)

Protein

Protein identifiers

Aspartate aminotransferase, cytoplasmic — P17174 (reviewed: P17174)

Alternative names: Cysteine aminotransferase, cytoplasmic, Cysteine transaminase, cytoplasmic, Glutamate oxaloacetate transaminase 1, Transaminase A

All UniProt accessions (2): P17174, A0A140VK69

UniProt curated annotations — full annotation on UniProt →

Function. Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. In addition, catalyzes (2S)-2-aminobutanoate, a by-product in the cysteine biosynthesis pathway.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Polymorphism. Genetic variations in GOT1 are associated with low serum aspartate aminotransferase and define the aspartate aminotransferase serum level quantitative trait locus 1 (ASTQTL1) [MIM:614419].

Miscellaneous. In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes. Aspartate aminotransferase activity found to be increased in cerebral spinal fluid (CSF) of patients with Alzheimer disease. Fetal serum levels of the enzyme in the umbilical artery and vein are found to be significantly higher than maternal serum levels.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P17174-1	1	yes
P17174-2	2

RefSeq proteins (1): NP_002070* (*=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)
• EC 2.6.1.64 — glutamine-phenylpyruvate transaminase (BRENDA: 7 organisms, 136 substrates, 15 inhibitors, 56 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

67 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-GLUTAMINE	0.6–3.5	4
L-PHENYLALANINE	1.1–6.6	3
L-TRYPTOPHAN	2.3–5	3
L-TYROSINE	1.43–1.6	3
L-METHIONINE	1.96–4.2	3
L-PHENYLALANINE	0.092–0.76	3
PYRUVATE	0.06–27	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

Catalyzed reactions (Rhea), 4 shown:

• L-cysteine + 2-oxoglutarate = 2-oxo-3-sulfanylpropanoate + L-glutamate (RHEA:17441)
• L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate (RHEA:21824)
• (2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L-glutamate (RHEA:70223)
• 3-sulfino-L-alanine + 2-oxoglutarate = 3-sulfinopyruvate + L-glutamate (RHEA:70295)

UniProt features (48 total): helix 18, strand 12, turn 7, binding site 4, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6DNB	X-RAY DIFFRACTION	1.7
8Z0E	X-RAY DIFFRACTION	1.82
3II0	X-RAY DIFFRACTION	2.05
6DND	X-RAY DIFFRACTION	2.1
6LIG	X-RAY DIFFRACTION	2.62
3WZF	X-RAY DIFFRACTION	2.99
6DNA	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17174-F1	96.42	0.95

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): 39; 141; 195; 387

Post-translational modifications (2): 149, 259

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1237112	Methionine salvage pathway
R-HSA-8963693	Aspartate and asparagine 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: 355 (showing top): MODULE_52, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (29): gluconeogenesis (GO:0006094), 2-oxoglutarate metabolic process (GO:0006103), oxaloacetate metabolic process (GO:0006107), glycerol biosynthetic process (GO:0006114), aspartate metabolic process (GO:0006531), L-aspartate biosynthetic process (GO:0006532), L-aspartate catabolic process (GO:0006533), glutamate metabolic process (GO:0006536), Notch signaling pathway (GO:0007219), response to carbohydrate (GO:0009743), obsolete L-glutamate catabolic process to aspartate (GO:0019550), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), cellular response to insulin stimulus (GO:0032869), negative regulation of collagen biosynthetic process (GO:0032966), response to immobilization stress (GO:0035902), malate-aspartate shuttle (GO:0043490), response to cadmium ion (GO:0046686), response to glucocorticoid (GO:0051384), negative regulation of cytosolic calcium ion concentration (GO:0051481), negative regulation of mitochondrial depolarization (GO:0051902), fatty acid homeostasis (GO:0055089), transdifferentiation (GO:0060290), cellular response to mechanical stimulus (GO:0071260), L-glutamate biosynthetic process (GO:0097054), response to transition metal nanoparticle (GO:1990267), amino acid metabolic process (GO:0006520), amino acid biosynthetic process (GO:0008652), biosynthetic process (GO:0009058), dicarboxylic acid metabolic process (GO:0043648)

GO Molecular Function (10): L-aspartate:2-oxoglutarate transaminase activity (GO:0004069), phosphatidylserine decarboxylase activity (GO:0004609), pyridoxal phosphate binding (GO:0030170), carboxylic acid binding (GO:0031406), L-cysteine:2-oxoglutarate transaminase activity (GO:0047801), (2S)-2-aminobutanoate:2-oxoglutarate transaminase activity (GO:0120554), catalytic activity (GO:0003824), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), axon terminus (GO:0043679), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	2
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
amino acid metabolic process	2
aspartate metabolic process	2
amino acid transaminase activity	2
anion binding	2
cellular anatomical structure	2
glucose metabolic process	1
hexose biosynthetic process	1
glycerol metabolic process	1
alditol biosynthetic process	1
aspartate family amino acid biosynthetic process	1
dicarboxylic acid biosynthetic process	1
dicarboxylic acid catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
cell surface receptor signaling pathway	1
response to oxygen-containing compound	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
response to insulin	1
cellular response to peptide hormone stimulus	1
negative regulation of biosynthetic process	1
negative regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
response to stress	1
L-aspartate:2-oxoglutarate transaminase activity	1
NAD+ metabolic process	1
L-malate dehydrogenase (NAD+) activity	1
mitochondrial transmembrane transport	1
response to metal ion	1
response to corticosteroid	1
regulation of biological quality	1
mitochondrial depolarization	1
regulation of mitochondrial depolarization	1
negative regulation of membrane depolarization	1
carboxy-lyase activity	1
vitamin B6 binding	1

Protein interactions and networks

STRING

2435 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GOT1	SULT1A3	P0DMM9	830
GOT1	SULT1A1	P50225	786
GOT1	SULT1A2	P50226	784
GOT1	ZIM2	Q9NZV7	784
GOT1	PGAM1	P18669	772
GOT1	GPT	P24298	772
GOT1	GPT2	Q8TD30	734
GOT1	GLUD1	P00367	717
GOT1	LDHAL6A	Q6ZMR3	703
GOT1	LDHAL6B	Q9BYZ2	702
GOT1	LDHC	P07864	682
GOT1	ALPG	P10696	673
GOT1	GGT7	Q9UJ14	656
GOT1	MDH2	P40926	645
GOT1	GGT6	Q6P531	634

IntAct

50 interactions, top by confidence:

A	B	Type	Score
EGFR	GOT1	psi-mi:“MI:0915”(physical association)	0.650
GOT1	EGFR	psi-mi:“MI:0915”(physical association)	0.650
GOT1	EGFR	psi-mi:“MI:2364”(proximity)	0.650
BRAF	MEN1	psi-mi:“MI:0914”(association)	0.600
GOT1	BRAF	psi-mi:“MI:0915”(physical association)	0.600
GOT1	BRAF	psi-mi:“MI:2364”(proximity)	0.600
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
DDAH2	OGT	psi-mi:“MI:0914”(association)	0.530
OSTF1	CHMP2A	psi-mi:“MI:0914”(association)	0.530
SERPINB8	TOX4	psi-mi:“MI:0914”(association)	0.530
SERPINB5	ALDH2	psi-mi:“MI:0914”(association)	0.530
IL36RN	UBB	psi-mi:“MI:0914”(association)	0.530
GOT1	RPL6	psi-mi:“MI:0915”(physical association)	0.400
S100A14	GOT1	psi-mi:“MI:0915”(physical association)	0.400
DMKN	GOT1	psi-mi:“MI:0915”(physical association)	0.400
PLA2G4D	GOT1	psi-mi:“MI:0915”(physical association)	0.400
PLBD1	GOT1	psi-mi:“MI:0915”(physical association)	0.400
TXNL1	GOT1	psi-mi:“MI:0915”(physical association)	0.400
GOT1	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
GOT1	CCR2	psi-mi:“MI:0915”(physical association)	0.370
GOT1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
GOT1	ABI3BP	psi-mi:“MI:0915”(physical association)	0.370
DAG1	AGRN	psi-mi:“MI:0914”(association)	0.350
GOT1L1	SERPINA1	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
NUTM2F	IRF6	psi-mi:“MI:0914”(association)	0.350
CDKN2A	NHERF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (289): GOT1 (Affinity Capture-RNA), GOT1 (Affinity Capture-RNA), GOT1 (Affinity Capture-RNA), ACP1 (Co-fractionation), ANXA11 (Co-fractionation), C11orf54 (Co-fractionation), CBR1 (Co-fractionation), CCS (Co-fractionation), FAHD1 (Co-fractionation), GLOD4 (Co-fractionation), GOT1 (Co-fractionation), GOT1 (Co-fractionation), GOT1 (Co-fractionation), GOT1 (Co-fractionation), GOT1 (Co-fractionation)

ESM2 similar proteins: A5A6K8, B9N1F9, O49299, P00503, P00504, P00949, P05201, P08906, P13221, P17174, P18757, P28011, P28734, P33097, P36871, P37833, P38652, P40939, P46645, P49724, P54767, P93804, P93805, Q01912, Q08DP0, Q0P5G4, Q28BL6, Q4R5E4, Q4R5L1, Q58FK9, Q5E9N4, Q5R691, Q5RFI8, Q640V9, Q6GML7, Q6YP21, Q71RI9, Q7T3E5, Q7TSV4, Q8N5Z0

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

9 interactions.

A	Effect	B	Mechanism
GOT1	“up-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
GOT1	“up-regulates quantity”	L-aspartate(1-)	“chemical modification”
GOT1	“up-regulates quantity”	oxaloacetate(2-)	“chemical modification”
GOT1	“up-regulates quantity”	L-glutamate(1-)	“chemical modification”
GOT1	“down-regulates quantity”	oxaloacetate(2-)	“chemical modification”
GOT1	“down-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
GOT1	“down-regulates quantity”	L-glutamate(1-)	“chemical modification”
GOT1	“down-regulates quantity”	L-aspartate(1-)	“chemical modification”
CEBPB	“up-regulates quantity by expression”	GOT1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
inflammatory response	9	6.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
29724	NM_002079.3(GOT1):c.1165_1167del (p.Asn389del)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:99402599:G:C	F361L	0.999
10:99402599:G:T	F361L	0.999
10:99402601:A:G	F361L	0.999
10:99402631:A:G	W351R	0.999
10:99402631:A:T	W351R	0.999
10:99403740:C:A	K259N	0.999
10:99403740:C:G	K259N	0.999
10:99403741:T:A	K259M	0.999
10:99402693:C:G	R330P	0.998
10:99403470:A:G	W320R	0.998
10:99403470:A:T	W320R	0.998
10:99403741:T:G	K259T	0.998
10:99405813:G:C	N195K	0.998
10:99405813:G:T	N195K	0.998
10:99406729:A:G	W141R	0.998
10:99406729:A:T	W141R	0.998
10:99420713:A:G	Y71H	0.998
10:99397622:G:C	N389K	0.997
10:99397622:G:T	N389K	0.997
10:99402600:A:G	F361S	0.997
10:99402601:A:T	F361I	0.997
10:99402629:C:A	W351C	0.997
10:99402629:C:G	W351C	0.997
10:99403542:A:G	W296R	0.997
10:99403542:A:T	W296R	0.997
10:99403742:T:C	K259E	0.997
10:99405782:A:G	W206R	0.997
10:99405782:A:T	W206R	0.997
10:99420697:C:A	G76V	0.997
10:99420698:C:G	G76R	0.997

dbSNP variants (sampled 300 via entrez): RS1000322922 (10:99430496 C>A,T), RS1000369476 (10:99416098 C>A,T), RS1000501085 (10:99424939 A>G), RS1000510853 (10:99421651 G>A), RS1000575634 (10:99423647 C>T), RS1000691977 (10:99428507 A>G), RS1000896205 (10:99412339 G>C,T), RS1001043737 (10:99418672 T>C), RS1001061038 (10:99428796 T>A,C,G), RS1001079404 (10:99399824 G>A,C), RS1001291214 (10:99399566 T>C), RS1001412658 (10:99398493 G>A), RS1001446395 (10:99399265 C>A,T), RS1001476068 (10:99400288 G>T), RS1001511994 (10:99405420 T>C)

Disease associations

OMIM: gene MIM:138180 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001222_1	Aspartate aminotransferase levels	3.000000e-14
GCST001438_10	Crohn’s disease	5.000000e-07
GCST002208_5	Liver enzyme levels (aspartate transaminase)	9.000000e-07
GCST003988_16	Hypothyroidism	1.000000e-10
GCST006011_80	Mean corpuscular volume	4.000000e-13
GCST007439_3	Aspartate aminotransferase levels	9.000000e-10
GCST010653_45	Thyroid stimulating hormone levels	6.000000e-35

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189139 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 61,725 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1265	ADAPALENE	4	12,179
CHEMBL276832	HYDRALAZINE	4	23,794
CHEMBL542541	HYDRALAZINE HYDROCHLORIDE	4	4,216
CHEMBL708	ZIPRASIDONE	4	21,536

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

ChEMBL bioactivities

9 potent at pChembl≥5 of 44 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.08	Kd	842	nM	CHEMBL5653589
6.08	ED50	842	nM	CHEMBL5653589
5.54	IC50	2920	nM	CHEMBL5182428
5.27	IC50	5390	nM	ZIPRASIDONE
5.23	IC50	5910	nM	CHEMBL5170907
5.17	Kd	6820	nM	CHEMBL3752910
5.17	ED50	6820	nM	CHEMBL3752910
5.10	IC50	8000	nM	CHEMBL5203489
5.09	IC50	8200	nM	CHEMBL4238792

PubChem BioAssay actives

7 with measured affinity, of 121 total; 7 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148451: Binding affinity to human GOT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8420	uM
(5Z)-3-[2,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]-4-hydroxy-5-[[4-hydroxy-3-(3-methylbut-2-enyl)phenyl]methylidene]furan-2-one	1850929: Inhibition of human recombinant GOT1 using aspartic acid and alpha-ketoglutaric acid as substrates incubated in presence of MDH1 and NADH	ic50	2.9200	uM
Ziprasidone	1850916: Inhibition of GOT1 (unknown origin)	ic50	5.3900	uM
(5Z)-4-hydroxy-3-[4-hydroxy-3-(3-methylbut-2-enyl)phenyl]-5-[[4-hydroxy-3-(3-methylbut-2-enyl)phenyl]methylidene]furan-2-one	1850930: Inhibition of C-terminal His6-tagged human recombinant GOT1 expressed in Escherichia coli BL21 (DE3) cells using aspartic acid and alpha-ketoglutaric acid as substrates incubated in presence of MDH1 and NADH	ic50	5.9100	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148451: Binding affinity to human GOT1 incubated for 45 mins by Kinobead based pull down assay	kd	6.8204	uM
3-amino-1-hydroxy-3,4-dihydroquinolin-2-one	1850916: Inhibition of GOT1 (unknown origin)	ic50	8.0000	uM
N-(4-chlorophenyl)-4-(1H-indol-4-yl)piperazine-1-carboxamide	1396144: Inhibition of GOT1 (unknown origin) using aspartate and alpha-ketoglutarate as substrate after 20 mins by MDH1 enzyme-coupled fluorescence assay	ic50	8.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
Cyclosporine	decreases expression, increases expression	4
Air Pollutants	affects expression, increases abundance, increases expression, decreases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	3
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	increases reaction, decreases reaction, increases activity, increases expression	2
Benzo(a)pyrene	increases expression	2
Diclofenac	affects expression, increases secretion	2
Estradiol	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	increases expression	2
aristolochic acid I	increases expression	1
aminomethylphosphonic acid (AMPA)	increases abundance, increases activity	1
gentian root extract	decreases reaction, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
N,N’-monomethylenebis(pyridiniumaldoxime)	increases secretion	1
sodium arsenate	decreases expression	1
titanium dioxide	affects binding, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
butylidenephthalide	increases expression	1
oltipraz	decreases reaction, increases activity	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2208563	Binding	Inhibition of aspartate aminotransferase using L-aspartate as substrate at 6 mM incubated for 1 hr prior to substrate addition measured after 30 mins by spectrophotometric analysis	(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent γ-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1WM	Abcam A-549 GOT1 KO	Cancer cell line	Male
CVCL_D2B0	Abcam HCT 116 GOT1 KO	Cancer cell line	Male
CVCL_SQ30	HAP1 GOT1 (-) 1	Cancer cell line	Male
CVCL_SQ31	HAP1 GOT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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