BCAT1

Summary

BCAT1 (branched chain amino acid transaminase 1, HGNC:976) is a protein-coding gene on chromosome 12p12.1, encoding Branched-chain-amino-acid aminotransferase, cytosolic (P54687). Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.

This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids to branched-chain L-amino acids essential for cell growth. Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia. As there is also a gene encoding a mitochondrial form of this enzyme, mutations in either gene may contribute to these disorders. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 586 — RefSeq curated summary.

At a glance

• GWAS associations: 133
• Clinical variants (ClinVar): 94 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_005504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:976
Approved symbol	BCAT1
Name	branched chain amino acid transaminase 1
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	BCATc
Ensembl gene	ENSG00000060982
Ensembl biotype	protein_coding
OMIM	113520
Entrez	586

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 1 non_stop_decay

ENST00000261192, ENST00000342945, ENST00000355164, ENST00000538118, ENST00000539282, ENST00000539780, ENST00000543099, ENST00000544418, ENST00000546285, ENST00000612790, ENST00000905145, ENST00000905146, ENST00000905147, ENST00000905148, ENST00000905149, ENST00000916642, ENST00000916643, ENST00000916644, ENST00000916645, ENST00000916646, ENST00000916647, ENST00000916648, ENST00000916649

RefSeq mRNA: 27 — MANE Select: NM_005504 NM_001178091, NM_001178092, NM_001178093, NM_001178094, NM_001413086, NM_001413087, NM_001413088, NM_001413089, NM_001413090, NM_001413091, NM_001413092, NM_001413093, NM_001413094, NM_001413095, NM_001413096, NM_001413097, NM_001413098, NM_001413099, NM_001413100, NM_001413101, NM_001413102, NM_001413103, NM_001413104, NM_001413105, NM_001413106, NM_001413107, NM_005504

CCDS: CCDS44845, CCDS53760, CCDS53761, CCDS53762, CCDS53763

Canonical transcript exons

ENST00000261192 — 11 exons

Exon	Start	End
ENSE00001314201	24832723	24832863
ENSE00001318494	24810024	24818049
ENSE00001535251	24948927	24949101
ENSE00003488334	24894275	24894475
ENSE00003494113	24901814	24901885
ENSE00003498820	24842082	24842224
ENSE00003535005	24878530	24878649
ENSE00003599243	24836511	24836596
ENSE00003606548	24849786	24849949
ENSE00003618684	24881301	24881411
ENSE00003677662	24829823	24829897

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.1840 / max 2235.3768, expressed in 1645 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130165	48.8386	1595
130154	6.5295	1001
130168	4.1117	1171
130166	2.1952	895
130151	1.8774	376
130152	1.5231	440
130148	0.6685	196
130147	0.6395	161
130135	0.4345	254
130150	0.4265	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.03	gold quality
synovial joint	UBERON:0002217	98.77	gold quality
pigmented layer of retina	UBERON:0001782	98.66	gold quality
retina	UBERON:0000966	98.64	gold quality
substantia nigra pars compacta	UBERON:0001965	97.37	gold quality
endothelial cell	CL:0000115	97.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.47	gold quality
tendon of biceps brachii	UBERON:0008188	96.01	gold quality
lower lobe of lung	UBERON:0008949	95.92	gold quality
visceral pleura	UBERON:0002401	95.69	gold quality
pons	UBERON:0000988	95.65	gold quality
cartilage tissue	UBERON:0002418	95.53	gold quality
parietal pleura	UBERON:0002400	95.11	gold quality
germinal epithelium of ovary	UBERON:0001304	93.95	gold quality
stromal cell of endometrium	CL:0002255	93.91	gold quality
superior vestibular nucleus	UBERON:0007227	93.84	gold quality
pleura	UBERON:0000977	93.69	gold quality
amniotic fluid	UBERON:0000173	93.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.45	gold quality
body of pancreas	UBERON:0001150	93.13	gold quality
sperm	CL:0000019	91.39	gold quality
lateral globus pallidus	UBERON:0002476	91.11	gold quality
endometrium	UBERON:0001295	91.05	gold quality
inferior vagus X ganglion	UBERON:0005363	90.72	gold quality
pericardium	UBERON:0002407	90.65	gold quality
middle temporal gyrus	UBERON:0002771	90.12	gold quality
ventral tegmental area	UBERON:0002691	90.08	gold quality
tendon	UBERON:0000043	89.92	gold quality
right lung	UBERON:0002167	89.51	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	993.30
E-MTAB-6075	yes	808.26
E-MTAB-5061	yes	337.14
E-MTAB-8142	yes	45.14
E-HCAD-10	yes	30.02
E-GEOD-81547	yes	27.19
E-GEOD-137537	yes	15.43
E-GEOD-100618	no	2156.95
E-CURD-53	no	179.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

340 targeting BCAT1, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3617-3P	99.98	67.86	918

Literature-anchored findings (GeneRIF, showing 40)

• Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced colorectal cancer (CRC). (PMID:17007058)
• The BCAT1 identified in the amplified 12p11-p12 region may play a certain role in nasopharyngeal carcinoma development. (PMID:18074675)
• hBCATc has redox mediated associations with several neuronal proteins involved in G-protein cell signaling, indicating a novel role for hBCATc in cellular redox control (PMID:18419134)
• The effect of nitric oxide modification on the functionality of human mitochondrial and cytosolic branched-chain aminotransferases (hBCATm and hBCATc, respectively) was investigated. (PMID:19119849)
• BCATc (cytosolic) has an overall redox potential that is 30 mV lower than BCATm (mitochondrial). Furthermore, the CXXC motif of BCATc was estimated to be 80 mV lower, suggesting that BCATm is more oxidizing in nature. (PMID:22107788)
• The mitochondrial isoform human brain BCAT 2 is largely confined to vascular endothelial cells, whereas the cytosolic human brain BCAT 1 is restricted to neurons. (PMID:23043456)
• Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma. (PMID:23758864)
• A central role for BCAT1 in glioma pathogenesis, making BCAT1 and branched-chain amino acids metabolism attractive targets for the development of targeted therapeutic approaches to treat patients with glioblastoma. (PMID:23793099)
• levels of branched-chain aminotransferase-1 (BCAT1) transcripts are significantly decreased on the polysomes of both RPS19 and RPL11 cells and that translation of BCAT1 protein is especially impaired in cells with small RP gene mutations (PMID:24463277)
• Focal deletions of the BCAT1 were associated with B-cell precursor acute lymphoblastic leukemia. (PMID:25261097)
• BCAT1 overexpression is associated with advanced tumour status, and implies adverse clinical outcomes of urothelial carcinoma (PMID:26173071)
• BCAT1 is strongly overexpressed in ovarian cancer. (PMID:26372729)
• Mechanistic investigation revealed that BCAT1 might be an important regulator responsible for DOT1L-mediated sphere formation and cell migration in breast cancer cells (PMID:26783998)
• BCAT1 plays a pathogenic role in hepatocellular carcinoma (HCC) by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC. (PMID:27246112)
• BCAT1 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• The tumor suppressive role of miR-218 was mediated by negatively regulating branched-chain amino acid transaminase 1 (BCAT1) protein expression. Importantly, overexpression of BCAT1 decreased the chemosensitivity to cis-diaminedichloroplatinum treatment of PC3 and DU145 cells. (PMID:28052414)
• It has been demonstrated that branched-chain amino acid (BCAA) catabolism is activated in human breast cancer, and abolishment of BCAA catabolism by knocking down BCAT1 inhibits breast cancer cell growth by repressing mTOR-mediated mitochondrial biogenesis and function. (PMID:28235484)
• Phenotypic analyses using a lentiviral-mediated BCAT1 short hairpin RNA knockdown revealed that BCAT1 sustains proliferation in addition to migration and invasion and that its overexpression enhanced the capacity of antiestrogen-sensitive cells to grow in the presence of antiestrogens. (PMID:28319069)
• regulatory role in macrophage function (PMID:28699638)
• by limiting intracellular alphaKG, BCAT1 links branched-chain amino acid catabolism to HIF1alpha stability and regulation of the epigenomic landscape, mimicking the effects of IDH mutations; results suggest the BCAA-BCAT1-alphaKG pathway as a therapeutic target to compromise leukaemia stem-cell function in patients with IDH(WT)TET2(WT) AML (PMID:29144447)
• Data suggest that both oncogenic mutations and cancer tissue-of-origin influence BCAA (branched-chain amino acid) metabolism in neoplastic tissue and neoplastic expression of cytosolic BCAT1 and mitochondrial BCAT2. (BCAT = branched-chain-amino-acid transaminase) [REVIEW] (PMID:29211698)
• up-regulation of BCAT1 indicated a poor survival rate of gastric cancer and may serve as a useful marker for predicting the outcome of patients with gastric cancer (PMID:29447920)
• Study has shown that BCAT1 and IKZF1 methylation are common events in colorectal cancer (CRC) with almost all cancer tissues showing significant levels of methylation in the two genes. The presence of ctDNA in blood is stage-related and show rapid reversion to negative following surgical resection. Monitoring methylated BCAT1 and IKZF1 levels could therefore inform adequacy of surgical resection. (PMID:29796114)
• BCAT1 overexpression may induce circulating tumor cells (CTC) release by triggering EMT and may be an important biomarker of hepatocellular carcinoma (HCC) metastasis. In liver cancer, CTC examination may represent an important “liquid biopsy” tool to detect both early disease and recurrent or metastatic disease, providing cues for early intervention or adjuvant therapy (PMID:29915159)
• Positive BCAT1 stain could be used to exclude diffuse gliomas with IDH1 codon 132 and IDH2 codon 172 mutations (PMID:30113684)
• Branched chain amino acid transaminase 1 (BCAT1) is overexpressed and hypomethylated in patients with non-alcoholic fatty liver disease who experience adverse clinical events (PMID:30265706)
• Our study identifies BCAT1 as a novel methylome signature distinguishing spindle/desmoplastic melanoma from cutaneous malignant peripheral nerve sheath tumor. (PMID:30310175)
• The high expression of c-myc may promote the invasion and metastasis of cervical cancer, and the high expression of bcat1 may promote the proliferation, invasion and metastasis of cervical cancer, which may have a synergistic effect in the pathogenesis of cervical cancer. (PMID:30378334)
• BCAT-induced autophagy regulates Abeta load through an interdependence of redox state and PKC phosphorylation-implications in Alzheimer’s disease. (PMID:31982508)
• Prognostic significance of branched-chain amino acid transferase 1 and CD133 in triple-negative breast cancer. (PMID:32571264)
• Tumour-reprogrammed stromal BCAT1 fuels branched-chain ketoacid dependency in stromal-rich PDAC tumours. (PMID:32694827)
• Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC). (PMID:32958500)
• BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages. (PMID:33148611)
• Differential expression of the BCAT isoforms between breast cancer subtypes. (PMID:33367952)
• Enrichment of branched chain amino acid transaminase 1 correlates with multiple biological processes and contributes to poor survival of IDH1 wild-type gliomas. (PMID:33493139)
• Variables Associated with Detection of Methylated BCAT1 or IKZF1 in Blood from Patients Without Colonoscopically Evident Colorectal Cancer. (PMID:33500319)
• BCAT1 overexpression regulates proliferation and cMyc/GLUT1 signaling in head and neck squamous cell carcinoma. (PMID:33760210)
• Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis. (PMID:34646394)
• A single nucleotide polymorphism in BCAT1 gene is associated with type 2 diabetes mellitus. (PMID:34932898)
• BCAT1: A risk factor in multiple cancers based on a pan-cancer analysis. (PMID:34984849)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcat1	ENSDARG00000045568
mus_musculus	Bcat1	ENSMUSG00000030268
rattus_norvegicus	Bcat1	ENSRNOG00000015514
drosophila_melanogaster	Bcat	FBGN0030482
caenorhabditis_elegans		WBGENE00001149
caenorhabditis_elegans		WBGENE00012855

Paralogs (1): BCAT2 (ENSG00000105552)

Protein

Protein identifiers

Branched-chain-amino-acid aminotransferase, cytosolic — P54687 (reviewed: P54687)

All UniProt accessions (3): P54687, A0A087WYF2, F5H2F2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. During embryogenesis, expressed in the brain and kidney. Overexpressed in MYC-induced tumors such as Burkitt’s lymphoma.

Activity regulation. The branched-chain-amino-acid aminotransferase, activity is inhibited by anticonvulsant drug gabapentin.

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

Isoforms (5)

UniProt ID	Names	Canonical?
P54687-1	1	yes
P54687-2	2
P54687-3	3
P54687-4	4
P54687-5	5

RefSeq proteins (27): NP_001171562, NP_001171563, NP_001171564, NP_001171565, NP_001400015, NP_001400016, NP_001400017, NP_001400018, NP_001400019, NP_001400020, NP_001400021, NP_001400022, NP_001400023, NP_001400024, NP_001400025, NP_001400026, NP_001400027, NP_001400028, NP_001400029, NP_001400030, NP_001400031, NP_001400032, NP_001400033, NP_001400034, NP_001400035, NP_001400036, NP_005495* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001544	Aminotrans_IV	Family
IPR005786	B_amino_transII	Family
IPR018300	Aminotrans_IV_CS	Conserved_site
IPR033939	BCAT_family	Family
IPR036038	Aminotransferase-like	Homologous_superfamily
IPR043131	BCAT-like_N	Homologous_superfamily
IPR043132	BCAT-like_C	Homologous_superfamily

Pfam: PF01063

Enzyme classification (BRENDA):

• EC 2.6.1.42 — branched-chain-amino-acid transaminase (BRENDA: 54 organisms, 371 substrates, 163 inhibitors, 313 Km, 171 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.085–16	55
L-LEUCINE	0.2–25	43
L-ISOLEUCINE	0.15–22.2	32
L-VALINE	0.22–143	31
L-GLUTAMATE	0.56–28.3	23
3-METHYL-2-OXOBUTANOIC ACID	0.15–7.09	8
3-METHYL-2-OXOPENTANOIC ACID	0.14–12.4	8
4-METHYL-2-OXOPENTANOIC ACID	0.22–11.65	8
2-OXOISOHEXANOATE	0.1–1.1	6
L-PHENYLALANINE	0.1–7.44	6
2-OXOISOPENTANOATE	0.33–0.56	5
4-METHYL-2-OXOPENTANOATE	0.045–2.64	5
2-OXOVALERATE	0.16–1	4
L-NORVALINE	0.32–4.7	4
3-METHYL-2-OXOBUTANOATE	0.11–2.69	3

Catalyzed reactions (Rhea), 3 shown:

• L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate (RHEA:18321)
• L-isoleucine + 2-oxoglutarate = (S)-3-methyl-2-oxopentanoate + L-glutamate (RHEA:24801)
• L-valine + 2-oxoglutarate = 3-methyl-2-oxobutanoate + L-glutamate (RHEA:24813)

UniProt features (55 total): strand 21, helix 12, sequence conflict 7, turn 5, splice variant 4, sequence variant 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
7NWA	X-RAY DIFFRACTION	1.59
7NY9	X-RAY DIFFRACTION	1.6
9BFO	X-RAY DIFFRACTION	1.66
7NXN	X-RAY DIFFRACTION	1.7
7NXO	X-RAY DIFFRACTION	1.71
9BFA	X-RAY DIFFRACTION	1.79
7NYA	X-RAY DIFFRACTION	1.85
2COI	X-RAY DIFFRACTION	1.9
2COG	X-RAY DIFFRACTION	2.1
7NWM	X-RAY DIFFRACTION	2.15
2ABJ	X-RAY DIFFRACTION	2.2
7NTR	X-RAY DIFFRACTION	2.23
7NY2	X-RAY DIFFRACTION	2.31
7NWC	X-RAY DIFFRACTION	2.38
2COJ	X-RAY DIFFRACTION	2.4
7NWE	X-RAY DIFFRACTION	2.54
7NWB	X-RAY DIFFRACTION	2.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54687-F1	95.05	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.

Post-translational modifications (2): 1, 222

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 0 (showing top):

GO Biological Process (8): G1/S transition of mitotic cell cycle (GO:0000082), lipid metabolic process (GO:0006629), branched-chain amino acid biosynthetic process (GO:0009082), branched-chain amino acid catabolic process (GO:0009083), L-leucine biosynthetic process (GO:0009098), L-valine biosynthetic process (GO:0009099), amino acid biosynthetic process (GO:0008652), branched-chain amino acid metabolic process (GO:0009081)

GO Molecular Function (8): branched-chain-amino-acid:2-oxoglutarate transaminase activity (GO:0004084), L-leucine:2-oxoglutarate transaminase activity (GO:0052654), L-valine:2-oxoglutarate transaminase activity (GO:0052655), L-isoleucine:2-oxoglutarate transaminase activity (GO:0052656), catalytic activity (GO:0003824), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
branched-chain-amino-acid:2-oxoglutarate transaminase activity	3
branched-chain amino acid metabolic process	2
pyruvate family amino acid biosynthetic process	2
branched-chain amino acid biosynthetic process	2
amino acid metabolic process	2
cellular anatomical structure	2
cytoplasm	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
primary metabolic process	1
carboxylic acid biosynthetic process	1
amino acid catabolic process	1
carboxylic acid catabolic process	1
L-leucine metabolic process	1
biosynthetic process	1
carboxylic acid metabolic process	1
amino acid transaminase activity	1
molecular_function	1
binding	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAT1	BCKDHA	P12694	657
BCAT1	MSI2	Q96DH6	628
BCAT1	BCKDHB	P21953	610
BCAT1	BCKDK	O14874	583
BCAT1	PSAT1	Q9Y617	572
BCAT1	ZNF177	Q13360	571
BCAT1	IDH1	O75874	570
BCAT1	MYC	P01106	551
BCAT1	THRB	P10828	548
BCAT1	PSPH	P78330	536
BCAT1	GLUD1	P00367	528
BCAT1	SHMT1	P34896	511
BCAT1	HIBADH	P31937	509
BCAT1	DBT	P11182	495
BCAT1	ASNS	P08184	495

IntAct

26 interactions, top by confidence:

A	B	Type	Score
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
BCAT1	ARNT	psi-mi:“MI:0914”(association)	0.530
GTF2A1	INPPL1	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
PRXL2B	NARS1	psi-mi:“MI:0914”(association)	0.530
MORN5	BCAT1	psi-mi:“MI:0914”(association)	0.530
BCAT1	TCF7L2	psi-mi:“MI:0915”(physical association)	0.400
BCAT1	SMAD5	psi-mi:“MI:0915”(physical association)	0.370
BCAT1	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
PRMT6	BCAT1	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
PROSER2	VWA8	psi-mi:“MI:0914”(association)	0.350
ADPRH	OBSL1	psi-mi:“MI:0914”(association)	0.350
MIF	PDHX	psi-mi:“MI:0914”(association)	0.350
PRKAR1B	DNAJC13	psi-mi:“MI:0914”(association)	0.350
PAPLN	SDHB	psi-mi:“MI:0914”(association)	0.350
GFOD1	SBF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): YEATS2 (Affinity Capture-MS), USP15 (Affinity Capture-MS), PRR14L (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), ZNHIT2 (Affinity Capture-MS), RAB3GAP1 (Affinity Capture-MS), HELZ (Affinity Capture-MS), PER1 (Affinity Capture-MS), PJA1 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), ARNT (Affinity Capture-MS)

ESM2 similar proteins: A7SLW1, B4G0F3, B8BKI7, B9SQI7, C6JS30, E0CSI1, E0CTF3, K7QHS5, K7QKH1, O15382, O22494, O23653, O23732, O35854, O35855, O80575, O81770, P0C7R2, P14019, P24288, P31166, P37821, P46416, P54687, P54690, P93115, Q10D00, Q2R483, Q5EA40, Q8GSJ1, Q93Y32, Q93Z70, Q948J9, Q9FIV6, Q9FKN4, Q9FN41, Q9FYA6, Q9FZL3, Q9FZL4, Q9GKM4

Diamond homologs: A0A179HME7, A0A1W5T1Y5, A0R066, A7SLW1, A9UZ24, C9K7B6, C9K7D8, K0E3V3, K7QHS5, K7QKH1, O14370, O15382, O26004, O27481, O31461, O32954, O35854, O35855, O86428, O86505, P0A1A5, P0A1A6, P0AB80, P0AB81, P0AB82, P24288, P38891, P39576, P47176, P54687, P54688, P54689, P54690, P63512, P63513, P74921, P99138, P9WQ74, P9WQ75, Q54N47

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	61
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1340043	GRCh37/hg19 12p12.1-11.22(chr12:23693737-29545102)x1	Pathogenic
695073	GRCh37/hg19 12p12.1(chr12:23457173-25177321)x1	Pathogenic

SpliceAI

3024 predictions. Top by Δscore:

Variant	Effect	Δscore
12:24818048:TA:T	acceptor_gain	1.0000
12:24818050:C:CC	acceptor_gain	1.0000
12:24829817:CTTTA:C	donor_loss	1.0000
12:24829818:TTTA:T	donor_loss	1.0000
12:24829819:TTA:T	donor_loss	1.0000
12:24829820:TAC:T	donor_loss	1.0000
12:24829821:ACCT:A	donor_loss	1.0000
12:24829822:CCTG:C	donor_loss	1.0000
12:24829893:ATTGT:A	acceptor_gain	1.0000
12:24829894:TTGT:T	acceptor_gain	1.0000
12:24829895:TGT:T	acceptor_gain	1.0000
12:24829896:GT:G	acceptor_gain	1.0000
12:24829896:GTCTA:G	acceptor_loss	1.0000
12:24829897:TC:T	acceptor_loss	1.0000
12:24829898:C:A	acceptor_loss	1.0000
12:24829898:C:CC	acceptor_gain	1.0000
12:24829899:T:C	acceptor_loss	1.0000
12:24832875:A:C	acceptor_gain	1.0000
12:24842224:CCTT:C	acceptor_gain	1.0000
12:24878533:AGTT:A	donor_gain	1.0000
12:24878646:ATACC:A	acceptor_loss	1.0000
12:24878647:TAC:T	acceptor_gain	1.0000
12:24878647:TACC:T	acceptor_loss	1.0000
12:24878648:ACC:A	acceptor_loss	1.0000
12:24878649:CCTGA:C	acceptor_loss	1.0000
12:24878650:C:CG	acceptor_loss	1.0000
12:24878651:T:A	acceptor_loss	1.0000
12:24881290:CA:C	donor_gain	1.0000
12:24881295:A:AC	donor_gain	1.0000
12:24881296:C:CC	donor_gain	1.0000

AlphaMissense

2499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:24894352:A:G	W68R	0.990
12:24894352:A:T	W68R	0.990
12:24842160:A:G	W247R	0.989
12:24842160:A:T	W247R	0.989
12:24894407:A:C	F49L	0.988
12:24894407:A:T	F49L	0.988
12:24894409:A:G	F49L	0.988
12:24842113:A:C	N262K	0.987
12:24842113:A:T	N262K	0.987
12:24881406:A:C	F95L	0.984
12:24881406:A:T	F95L	0.984
12:24881408:A:G	F95L	0.984
12:24832780:A:C	F329L	0.983
12:24832780:A:T	F329L	0.983
12:24832782:A:G	F329L	0.983
12:24849794:C:A	K222N	0.983
12:24849794:C:G	K222N	0.983
12:24894350:C:A	W68C	0.983
12:24894350:C:G	W68C	0.983
12:24878609:A:G	L144P	0.982
12:24832748:A:T	V340D	0.981
12:24836542:C:A	R291M	0.979
12:24842116:C:A	M261I	0.976
12:24842116:C:G	M261I	0.976
12:24842116:C:T	M261I	0.976
12:24881404:T:A	E96V	0.976
12:24842221:A:C	N226K	0.975
12:24842221:A:T	N226K	0.975
12:24849824:T:A	R212S	0.975
12:24849824:T:G	R212S	0.975

dbSNP variants (sampled 300 via entrez): RS1000008223 (12:24880383 G>A), RS1000009822 (12:24841106 G>A), RS1000059275 (12:24930873 T>C), RS1000075373 (12:24832202 A>G), RS1000076945 (12:24888687 A>AGAAGG), RS1000110117 (12:24846689 T>C), RS1000114576 (12:24814160 T>A), RS1000169992 (12:24823594 G>A), RS1000189273 (12:24855338 A>G), RS1000224175 (12:24846485 G>T), RS1000230787 (12:24944078 T>C), RS1000250829 (12:24814388 T>A), RS1000257131 (12:24897276 C>A,T), RS1000257692 (12:24938235 G>A), RS1000281074 (12:24832439 G>A)

Disease associations

OMIM: gene MIM:113520 | disease phenotypes: MIM:616803

GenCC curated gene-disease

Mondo (1): Lamb-Shaffer syndrome (MONDO:0014778)

Orphanet (3): 12p12.1 microdeletion syndrome (Orphanet:313884), Developmental and speech delay due to SOX5 deficiency (Orphanet:313892), Lamb-Shaffer syndrome (Orphanet:530983)

HPO phenotypes

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

GWAS associations

133 associations (top):

Study	Trait	p-value
GCST000635_33	Response to statin therapy	2.000000e-06
GCST001859_49	Thiazide-induced adverse metabolic effects in hypertensive patients	6.000000e-06
GCST002911_11	Calcium levels	9.000000e-06
GCST003449_4	Erythrocyte cadmium concentration	8.000000e-06
GCST005845_7	Heart rate increase in response to exercise	6.000000e-28
GCST005846_12	Heart rate response to recovery post exercise (10 sec)	1.000000e-19
GCST005847_13	Heart rate response to recovery post exercise (20 sec)	2.000000e-19
GCST005848_1	Heart rate response to recovery post exercise (50 sec)	1.000000e-26
GCST005849_4	Heart rate response to recovery post exercise (40 sec)	1.000000e-28
GCST005850_10	Heart rate response to recovery post exercise (30 sec)	2.000000e-22
GCST006061_116	Atrial fibrillation	1.000000e-25
GCST006061_117	Atrial fibrillation	1.000000e-21
GCST006617_3	Uterine fibroid size (maximum volume)	6.000000e-07
GCST006626_23	Pulse pressure	6.000000e-12
GCST007226_13	PR interval	6.000000e-13
GCST007324_118	Adventurousness	2.000000e-08
GCST007540_8	PEG-asparaginase hypersensitivity without enzyme activity in childhood acute lymphoblastic leukaemia	3.000000e-06
GCST009665_17	Breast cancer	3.000000e-06
GCST010321_143	PR interval	2.000000e-138
GCST010321_168	PR interval	1.000000e-13
GCST010796_1	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-51
GCST010796_1271	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_1272	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_1273	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_1274	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_1275	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1301	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1302	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1303	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_1304	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0009410	uterine fibroid measurement
EFO:0005763	pulse pressure measurement
EFO:0004462	PR interval
EFO:0008579	risk-taking behaviour
EFO:0004881	asparaginase hypersensitivity
EFO:0004327	electrocardiography
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4679 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.6.1.42 Branched-chain-amino-acid transaminase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
BAY-069	Inhibition	7.51	pIC50

ChEMBL bioactivities

63 potent at pChembl≥5 of 81 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.57	IC50	27	nM	BAY-069
7.51	IC50	31	nM	BAY-069
7.22	IC50	60	nM	CHEMBL5220763
7.20	IC50	63.1	nM	CHEMBL3617085
7.16	IC50	70	nM	CHEMBL5219349
7.05	IC50	90	nM	CHEMBL5219349
6.92	IC50	120	nM	CHEMBL5220953
6.84	IC50	145	nM	CHEMBL5218588
6.82	IC50	150	nM	CHEMBL5220319
6.80	IC50	159	nM	CHEMBL5218805
6.79	IC50	162	nM	CHEMBL5220178
6.75	IC50	180	nM	CHEMBL5219314
6.75	IC50	180	nM	CHEMBL5219436
6.73	IC50	186	nM	BAY-069
6.70	IC50	200	nM	CHEMBL5220903
6.70	IC50	200	nM	CHEMBL5219261
6.70	IC50	200	nM	CHEMBL5220805
6.70	IC50	200	nM	CHEMBL5219436
6.64	IC50	230	nM	CHEMBL1231666
6.60	IC50	251.2	nM	CHEMBL3617078
6.54	IC50	287	nM	CHEMBL5220488
6.47	IC50	340	nM	CHEMBL5219683
6.45	IC50	358	nM	BAY-069
6.40	IC50	400	nM	CHEMBL5218519
6.40	IC50	400	nM	CHEMBL5219436
6.38	IC50	413	nM	CHEMBL5219699
6.36	IC50	438	nM	CHEMBL5220057
6.29	IC50	507	nM	CHEMBL5219137
6.26	IC50	554	nM	CHEMBL5220817
6.16	IC50	700	nM	CHEMBL5219393
6.14	IC50	723	nM	CHEMBL5219459
6.14	IC50	725	nM	CHEMBL5220789
6.10	IC50	800	nM	CHEMBL205903
6.10	IC50	800	nM	CHEMBL5218966
6.10	IC50	792	nM	CHEMBL5219673
6.07	IC50	850	nM	CHEMBL5220587
6.05	IC50	900	nM	CHEMBL5220979
6.03	IC50	925	nM	CHEMBL5219169
6.00	IC50	1000	nM	CHEMBL5219665
5.94	IC50	1160	nM	CHEMBL207636
5.92	IC50	1200	nM	CHEMBL427026
5.90	IC50	1259	nM	CHEMBL3809237
5.75	IC50	1800	nM	CHEMBL5219930
5.72	IC50	1900	nM	CHEMBL5218682
5.64	IC50	2300	nM	CHEMBL5219636
5.63	IC50	2350	nM	CHEMBL205902
5.63	IC50	2320	nM	BAY-069
5.60	IC50	2500	nM	CHEMBL377308
5.55	IC50	2800	nM	CHEMBL437702
5.50	IC50	3200	nM	CHEMBL205475

PubChem BioAssay actives

58 with measured affinity, of 84 total; 50 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
3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.0310	uM
4-[6-(benzenesulfonyl)-2,4-dioxo-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.0600	uM
5-butyl-2-[(4-chloro-2,6-difluorophenyl)methylamino]-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246080: Inhibition of BCATc (unknown origin)	ic50	0.0631	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)naphthalene-1-carbonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.0700	uM
5-chloro-4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1200	uM
4-[6-[difluoro(phenyl)methyl]-2,4-dioxo-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1450	uM
4-[6-(difluoromethyl)-2,4-dioxo-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1500	uM
2-(2-chlorophenoxy)-4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-fluorobenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1590	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1620	uM
3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-[difluoro(phenyl)methyl]-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1800	uM
4-(6-cyclopropyl-2,4-dioxo-1H-pyrimidin-3-yl)-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1800	uM
5-bromo-4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.2000	uM
4-(6-bromo-2,4-dioxo-1H-pyrimidin-3-yl)-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.2000	uM
4-[6-[chloro(difluoro)methyl]-2,4-dioxo-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.2000	uM
5-chloro-N’-[2-(trifluoromethyl)phenyl]sulfonyl-1-benzofuran-2-carbohydrazide	617744: Inhibition of human recombinant histidine-tagged BCATc expressed in Escherichia coli BL21 (DE3) after 50 mins using [13C]-L-leucine as substrate by NMR spectroscopy analysis	ic50	0.2300	uM
2-[(4-chloro-2,6-difluorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246080: Inhibition of BCATc (unknown origin)	ic50	0.2512	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-methyl-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.2870	uM
2-(2,6-dimethylphenoxy)-4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-fluorobenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.3400	uM
2-(2-chloro-6-methylphenoxy)-4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-fluorobenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.4000	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-iodo-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.4130	uM
3-[4-chloro-2-methoxy-5-(2-methylphenoxy)phenyl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.4380	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.5070	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-fluoro-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.5540	uM
5-methoxy-2-(2-methylphenoxy)-4-(6-methylsulfonyl-2,4-dioxo-1H-pyrimidin-3-yl)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.7000	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)-5-propoxybenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.7230	uM
4-(2,4-dioxo-6-phenyl-1H-pyrimidin-3-yl)-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.7250	uM
4-[2,4-dioxo-6-(1,1,2,2,2-pentafluoroethyl)-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.7920	uM
2-(2,6-difluorophenoxy)-4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-fluorobenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.8000	uM
5-chloro-N’-[2-(trifluoromethyl)phenyl]sulfonyl-1H-indole-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	0.8000	uM
3-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-N-methyl-2-pyridin-2-ylimidazo[1,2-a]pyridine-7-carboxamide	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.8500	uM
3-[4-cyano-2-methoxy-5-(2-methylphenoxy)phenyl]-2,4-dioxo-1H-pyrimidine-6-carboxamide	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.9000	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)-5-(trifluoromethoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.9250	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-fluoro-2-phenoxybenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	1.0000	uM
5-chloro-N’-(2-methylphenyl)sulfonyl-1H-indole-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	1.1600	uM
5-chloro-N’-(3-methylphenyl)sulfonyl-1H-indole-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	1.2000	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-(2-methylsulfanylphenyl)benzimidazole-5-carboxamide	1303048: Inhibition of BCATc (unknown origin)	ic50	1.2589	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-hydroxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	1.8000	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-ethyl-6-methylphenoxy)-5-fluorobenzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	1.9000	uM
3-[2-fluoro-4-methyl-5-(2-methylphenoxy)phenyl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	2.3000	uM
N’-(benzenesulfonyl)dibenzofuran-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	2.3500	uM
N’-(benzenesulfonyl)-5-bromo-1-benzofuran-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	2.5000	uM
N’-(3-methylphenyl)sulfonyldibenzofuran-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	2.8000	uM
N’-(2-methylphenyl)sulfonyldibenzofuran-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	3.2000	uM
3-(5-chloro-2,4-dimethoxyphenyl)-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	3.3000	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303048: Inhibition of BCATc (unknown origin)	ic50	3.9811	uM
3-[2-chloro-5-(2-methylphenoxy)phenyl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	4.0000	uM
N’-(benzenesulfonyl)-5-chloro-1-benzofuran-2-carbohydrazide	263857: Inhibition of human BCATc	ic50	4.2000	uM
4-[2,4-dioxo-6-[4-(trifluoromethyl)phenyl]-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	4.5000	uM
3-[2-methoxy-5-(2-methylphenoxy)phenyl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918059: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	4.6000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147942: Binding affinity to human BCAT1 incubated for 45 mins by Kinobead based pull down assay	kd	4.9991	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, affects cotreatment, decreases expression, increases methylation	7
Cyclosporine	increases expression	6
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases methylation	5
Tretinoin	decreases expression	4
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression	3
sodium arsenite	increases expression, decreases expression, increases abundance	3
(+)-JQ1 compound	decreases expression	3
Cisplatin	decreases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression, increases methylation	3
Cadmium Chloride	increases expression	3
Formaldehyde	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tunicamycin	increases expression	2
Valproic Acid	decreases expression	2
Thapsigargin	increases expression	2
beta-Naphthoflavone	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
chloroacetaldehyde	affects expression	1
benzo(b)fluoranthene	affects cotreatment, decreases expression	1
arsenite	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
benz(a)anthracene	affects cotreatment, decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1825867	Binding	Inhibition of human recombinant histidine-tagged BCATc expressed in Escherichia coli BL21 (DE3) after 50 mins using [13C]-L-leucine as substrate by NMR spectroscopy analysis	Cracking the molecular weight barrier: fragment screening of an aminotransferase using an NMR-based functional assay. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1LN	Abcam K-562 BCAT1 KO	Cancer cell line	Female
CVCL_D2I9	Abcam Raji BCAT1 KO	Cancer cell line	Male
CVCL_E0TR	Ubigene Hep G2 BCAT1 KO	Cancer cell line	Male
CVCL_E0VG	Ubigene Huh-7 BCAT1 KO	Cancer cell line	Male
CVCL_E1RV	HAP1 BCAT1 (-) 1	Cancer cell line	Male
CVCL_E1RW	HAP1 BCAT1 (-) 2	Cancer cell line	Male
CVCL_E4P0	KOLF2.1J BCAT1 65.2kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_UQ20	Abcam Jurkat BCAT1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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