BCAT2

Summary

BCAT2 (branched chain amino acid transaminase 2, HGNC:977) is a protein-coding gene on chromosome 19q13.33, encoding Branched-chain-amino-acid aminotransferase, mitochondrial (O15382). Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.

This gene encodes a branched chain aminotransferase found in mitochondria. The encoded protein forms a dimer that catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 587 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypervalinemia and hyperleucine-isoleucinemia (Definitive, ClinGen)
• GWAS associations: 47
• Clinical variants (ClinVar): 340 total — 11 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_001190

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:977
Approved symbol	BCAT2
Name	branched chain amino acid transaminase 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	BCAM, BCATm
Ensembl gene	ENSG00000105552
Ensembl biotype	protein_coding
OMIM	113530
Entrez	587

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 26 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000316273, ENST00000402551, ENST00000545387, ENST00000593515, ENST00000595376, ENST00000596981, ENST00000597011, ENST00000598162, ENST00000599246, ENST00000599510, ENST00000601496, ENST00000601681, ENST00000869275, ENST00000869276, ENST00000869277, ENST00000869278, ENST00000869279, ENST00000869280, ENST00000869281, ENST00000869282, ENST00000917096, ENST00000917097, ENST00000917098, ENST00000917099, ENST00000917100, ENST00000917101, ENST00000917102, ENST00000917103, ENST00000971045, ENST00000971046

RefSeq mRNA: 3 — MANE Select: NM_001190 NM_001164773, NM_001190, NM_001284325

CCDS: CCDS12735, CCDS54290, CCDS74416

Canonical transcript exons

ENST00000316273 — 11 exons

Exon	Start	End
ENSE00000718200	48797191	48797333
ENSE00000718205	48799675	48799838
ENSE00000853351	48796428	48796502
ENSE00003187032	48795064	48795464
ENSE00003472504	48796578	48796718
ENSE00003516316	48796937	48797022
ENSE00003527438	48807000	48807074
ENSE00003562040	48810984	48811029
ENSE00003610140	48806517	48806717
ENSE00003625849	48799981	48800100
ENSE00003673181	48800187	48800297

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.5557 / max 162.4997, expressed in 1786 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181933	22.4521	1783
181934	1.5288	1125
181932	1.0306	392
181931	0.5277	268
181929	0.0166	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	97.16	gold quality
right adrenal gland	UBERON:0001233	97.13	gold quality
left adrenal gland	UBERON:0001234	96.48	gold quality
mucosa of transverse colon	UBERON:0004991	96.25	gold quality
left adrenal gland cortex	UBERON:0035825	96.23	gold quality
adrenal cortex	UBERON:0001235	95.68	gold quality
body of pancreas	UBERON:0001150	95.63	gold quality
body of stomach	UBERON:0001161	95.36	gold quality
right ovary	UBERON:0002118	95.26	gold quality
left ovary	UBERON:0002119	95.13	gold quality
apex of heart	UBERON:0002098	94.66	gold quality
mucosa of stomach	UBERON:0001199	94.47	gold quality
adrenal gland	UBERON:0002369	94.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.15	gold quality
cerebellar hemisphere	UBERON:0002245	93.96	gold quality
heart left ventricle	UBERON:0002084	93.95	gold quality
tibial nerve	UBERON:0001323	93.85	gold quality
cerebellar cortex	UBERON:0002129	93.78	gold quality
cardiac ventricle	UBERON:0002082	93.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.53	gold quality
lower esophagus	UBERON:0013473	93.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.27	gold quality
transverse colon	UBERON:0001157	93.14	gold quality
stomach	UBERON:0000945	93.12	gold quality
gastrocnemius	UBERON:0001388	92.98	gold quality
right lobe of liver	UBERON:0001114	92.59	gold quality
left uterine tube	UBERON:0001303	92.53	gold quality
right lung	UBERON:0002167	92.37	gold quality
buccal mucosa cell	CL:0002336	92.24	gold quality
muscle of leg	UBERON:0001383	92.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.01
E-MTAB-7303	no	196.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting BCAT2, 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-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-7703	97.64	67.00	965
HSA-MIR-4642	97.52	67.60	916

Literature-anchored findings (GeneRIF, showing 17)

• identification of a peroxide-sensitive redox switch at the CXXC motif (PMID:12119021)
• Studies of ketimine and pyridoxamine phosphate forms of BCAT@ reaction intermediates reveal substrate specificity for L-branched chain amino acids via a group of hydrophobic residues that form three hydrophobic surfaces and lock the side chain in place. (PMID:12269802)
• role of cysteine residues in the regulatory CXXC motif (PMID:15182179)
• ption of the CXXC center results in altered substrate orientation and deprotonation of the amino group of pyridoxamine 5’-phosphate, which inhibits catalysis (PMID:17050531)
• 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)
• 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)
• Skeletal muscle amino acid transporter and BCAT2 expression prior to and following interval running or resistance exercise in mode-specific trained males. (PMID:29725856)
• The crystal structure of the oxidized form of the C318A variant of the human mitochondrial branched-chain aminotransferase was used to better understand the contributions of the individual cysteines and their oxidation states. (PMID:31929181)
• BCAT2-mediated branched-chain amino acids catabolism is critical for the development of pancreatic ductal adenocarcinoma-harboring KRAS mutations. (PMID:32029896)
• Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. (PMID:32467562)
• Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells. (PMID:33097833)
• Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance. (PMID:34340727)
• Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults. (PMID:34511290)
• BCAT2 promotes melanoma progression by activating lipogenesis via the epigenetic regulation of FASN and ACLY expressions. (PMID:37801083)
• Deficiency of BCAT2-mediated branched-chain amino acid catabolism promotes colorectal cancer development. (PMID:37926361)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcat2	ENSDARG00000054849
mus_musculus	Bcat2	ENSMUSG00000030826
rattus_norvegicus	Bcat2	ENSRNOG00000020956
drosophila_melanogaster	Bcat	FBGN0030482
caenorhabditis_elegans		WBGENE00001149
caenorhabditis_elegans		WBGENE00012855

Paralogs (1): BCAT1 (ENSG00000060982)

Protein

Protein identifiers

Branched-chain-amino-acid aminotransferase, mitochondrial — O15382 (reviewed: O15382)

Alternative names: Placental protein 18

All UniProt accessions (6): O15382, B3KSI3, M0QXF9, M0QZ10, M0QZP4, M0R2K7

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. Branched chain amino acid catabolism plays a role in adipocyte differentiation by providing lipogenic acetyl-CoA pools in differentiated adipocytes. Mechanistically, acetyl-CoA derived from branched chain amino acid catabolism is used by EP300/p300 to acetylate and inhibit PRDM16, thereby preventing adipose tissue browning. May also function as a transporter of branched chain alpha-keto acids.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitous.

Disease relevance. Hypervalinemia and hyperleucine-isoleucinemia (HVLI) [MIM:618850] An autosomal recessive metabolic disorder characterized by highly elevated plasma concentrations of valine and leucine/isoleucine. Affected individuals suffer from headache and mild memory impairment. The disease is caused by variants affecting the gene represented in this entry. A patient with hypervalinemia and hyperleucine-isoleucinemia was identified as compound heterozygote for Gln-170 (inherited from his father) and Lys-264 (inherited from his mother), both variants reduced the catalytic activity of the enzyme. After treatment with vitamin B6, a precursor of pyridoxal 5’-phosphate, a BCAT2 cofactor, the blood levels of branched chain amino acids, especially valine, were decreased and brain lesions were improved.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O15382-1	A	yes
O15382-2	B

RefSeq proteins (3): NP_001158245, NP_001181, NP_001271254 (=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 (67 total): strand 23, helix 13, sequence conflict 9, sequence variant 6, binding site 6, turn 3, mutagenesis site 2, modified residue 2, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
5MPR	X-RAY DIFFRACTION	1.6
5CR5	X-RAY DIFFRACTION	1.61
5I5X	X-RAY DIFFRACTION	1.65
5BWX	X-RAY DIFFRACTION	1.7
2A1H	X-RAY DIFFRACTION	1.8
2HG8	X-RAY DIFFRACTION	1.8
2HGX	X-RAY DIFFRACTION	1.8
2HHF	X-RAY DIFFRACTION	1.8
5I5Y	X-RAY DIFFRACTION	1.81
5BWW	X-RAY DIFFRACTION	1.82
5BWV	X-RAY DIFFRACTION	1.86
1KT8	X-RAY DIFFRACTION	1.9
1KTA	X-RAY DIFFRACTION	1.9
5I5V	X-RAY DIFFRACTION	1.94
1EKF	X-RAY DIFFRACTION	1.95
2HGW	X-RAY DIFFRACTION	1.98
9LEP	X-RAY DIFFRACTION	2
5HNE	X-RAY DIFFRACTION	2.04
5I5S	X-RAY DIFFRACTION	2.06
5I60	X-RAY DIFFRACTION	2.12
5BWU	X-RAY DIFFRACTION	2.17
5BWR	X-RAY DIFFRACTION	2.2
5BWT	X-RAY DIFFRACTION	2.2
1EKV	X-RAY DIFFRACTION	2.25
5I5T	X-RAY DIFFRACTION	2.31
2HDK	X-RAY DIFFRACTION	2.4
5I5W	X-RAY DIFFRACTION	2.4
5I5U	X-RAY DIFFRACTION	2.4
1EKP	X-RAY DIFFRACTION	2.5
6PRX	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15382-F1	93.47	0.90

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 (6): 126; 168; 234; 296; 297; 340

Post-translational modifications (2): 229, 321

Mutagenesis-validated functional residues (2):

Position	Phenotype
342	reduces activity about 6-fold.
345	slight reduction of activity.

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: 424 (showing top): KOBAYASHI_EGFR_SIGNALING_24HR_UP, GRUETZMANN_PANCREATIC_CANCER_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, ROVERSI_GLIOMA_COPY_NUMBER_UP, CAIRO_PML_TARGETS_BOUND_BY_MYC_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, RODRIGUES_NTN1_TARGETS_DN, GCM_MYCL1

GO Biological Process (14): L-isoleucine catabolic process (GO:0006550), 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), regulation of hormone levels (GO:0010817), brown fat cell differentiation (GO:0050873), cellular response to leukemia inhibitory factor (GO:1990830), obsolete isoleucine metabolic process (GO:0006549), L-leucine metabolic process (GO:0006551), obsolete valine metabolic process (GO:0006573), 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): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

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 metabolic process	3
branched-chain-amino-acid:2-oxoglutarate transaminase activity	3
pyruvate family amino acid biosynthetic process	2
branched-chain amino acid biosynthetic process	2
amino acid metabolic process	2
branched-chain amino acid catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	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
regulation of biological quality	1
fat cell differentiation	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
L-amino acid metabolic process	1
proteinogenic amino acid 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
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

2702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAT2	BCKDHA	P12694	934
BCAT2	BCKDHB	P21953	909
BCAT2	BCKDK	O14874	729
BCAT2	PPM1K	Q8N3J5	621
BCAT2	KLF15	Q9UIH9	597
BCAT2	DBT	P11182	585
BCAT2	HIBADH	P31937	559
BCAT2	THRB	P10828	543
BCAT2	GLUD1	P00367	518
BCAT2	GLUL	P15104	510
BCAT2	IVD	P26440	506
BCAT2	PSAT1	Q9Y617	506
BCAT2	ACADSB	P45954	501
BCAT2	ALDH6A1	Q02252	501
BCAT2	PCCB	P05166	491

IntAct

35 interactions, top by confidence:

A	B	Type	Score
BCAT2	HSPD1	psi-mi:“MI:0915”(physical association)	0.780
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
YBEY	BCAT2	psi-mi:“MI:0915”(physical association)	0.670
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
EEF2KMT	BCAT2	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
BCAT2	BCAT2	psi-mi:“MI:0407”(direct interaction)	0.440
PEA15	BCAT2	psi-mi:“MI:0915”(physical association)	0.400
BCAT2	NDUFB9	psi-mi:“MI:0915”(physical association)	0.400
BCAT2	ALDOA	psi-mi:“MI:0915”(physical association)	0.370
BCAT2	PTGDS	psi-mi:“MI:0915”(physical association)	0.370
CREB3	BCAT2	psi-mi:“MI:0915”(physical association)	0.370
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
NIT1	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CELA3B	BCAT2	psi-mi:“MI:0914”(association)	0.350
IMPDH1	MGST3	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): BCAT2 (Affinity Capture-MS), BCAT2 (Co-fractionation), BCAT2 (Co-fractionation), CAT (Co-fractionation), UFM1 (Co-fractionation), BCAT2 (Affinity Capture-MS), BCAT2 (Affinity Capture-MS), BCAT2 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), BCAT2 (Affinity Capture-MS), BCAT2 (Affinity Capture-RNA), MMP25 (Negative Genetic), PRKDC (Negative Genetic), PTK6 (Negative Genetic), POMC (Negative Genetic)

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

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	3
Uncertain significance	197
Likely benign	67
Benign	23

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1980342	NM_001190.4(BCAT2):c.600C>A (p.Tyr200Ter)	Pathogenic
3338118	NM_001190.4(BCAT2):c.545T>G (p.Val182Gly)	Pathogenic
3338121	NM_001190.4(BCAT2):c.136_147del (p.His46_Pro49del)	Pathogenic
3338122	BCAT2, INS/DEL, NT1154	Pathogenic
440	NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)	Pathogenic
441	NG_007480.1:g.(7267_8082)_(8469_9169)del	Pathogenic
442	NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)	Pathogenic
443	NM_005581.5(BCAM):c.361C>T (p.Arg121Ter)	Pathogenic
4782124	NM_001190.4(BCAT2):c.821G>A (p.Trp274Ter)	Pathogenic
869184	NM_001190.4(BCAT2):c.509G>A (p.Arg170Gln)	Pathogenic
869185	NM_001190.4(BCAT2):c.790G>A (p.Glu264Lys)	Pathogenic
2730562	NM_001190.4(BCAT2):c.696-2A>G	Likely pathogenic
3892999	NM_005581.5(BCAM):c.880dup (p.Asp294fs)	Likely pathogenic
980767	GRCh37/hg19 19q13.33(chr19:48854319-49430535)x3	Likely pathogenic

SpliceAI

2438 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48795465:C:CC	acceptor_gain	1.0000
19:48796422:GCTCA:G	donor_loss	1.0000
19:48796423:CTCA:C	donor_loss	1.0000
19:48796424:TCA:T	donor_loss	1.0000
19:48796425:CAC:C	donor_loss	1.0000
19:48796426:A:AC	donor_gain	1.0000
19:48796426:A:AG	donor_loss	1.0000
19:48796427:C:A	donor_loss	1.0000
19:48796427:C:CC	donor_gain	1.0000
19:48796498:AGGTT:A	acceptor_gain	1.0000
19:48796499:GGTT:G	acceptor_gain	1.0000
19:48796500:GTT:G	acceptor_gain	1.0000
19:48796500:GTTCT:G	acceptor_loss	1.0000
19:48796501:TT:T	acceptor_gain	1.0000
19:48796502:TC:T	acceptor_loss	1.0000
19:48796503:C:CA	acceptor_loss	1.0000
19:48796503:C:CC	acceptor_gain	1.0000
19:48796504:T:G	acceptor_loss	1.0000
19:48796576:AC:A	donor_gain	1.0000
19:48796577:CC:C	donor_gain	1.0000
19:48797029:CAGG:C	acceptor_gain	1.0000
19:48797032:G:C	acceptor_gain	1.0000
19:48797032:G:GC	acceptor_gain	1.0000
19:48797189:AC:A	donor_gain	1.0000
19:48797190:CC:C	donor_gain	1.0000
19:48799979:ACCT:A	donor_loss	1.0000
19:48799980:CCTCG:C	donor_loss	1.0000
19:48800099:CT:C	acceptor_gain	1.0000
19:48800101:C:CC	acceptor_gain	1.0000
19:48800357:C:CT	acceptor_gain	1.0000

AlphaMissense

2534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48797222:G:C	N269K	0.997
19:48797222:G:T	N269K	0.997
19:48799683:C:A	K229N	0.997
19:48799683:C:G	K229N	0.997
19:48796961:A:C	S300R	0.996
19:48796961:A:T	S300R	0.996
19:48796963:T:G	S300R	0.996
19:48797269:A:G	W254R	0.996
19:48797269:A:T	W254R	0.996
19:48797330:A:C	N233K	0.996
19:48797330:A:T	N233K	0.996
19:48800290:T:A	E103V	0.996
19:48800292:A:C	F102L	0.996
19:48800292:A:T	F102L	0.996
19:48800294:A:G	F102L	0.996
19:48800221:C:G	R126P	0.995
19:48806594:A:G	W75R	0.995
19:48806594:A:T	W75R	0.995
19:48799685:T:C	K229E	0.994
19:48800060:A:G	L151P	0.994
19:48796968:C:A	R298I	0.990
19:48797238:T:A	E264V	0.990
19:48799684:T:A	K229M	0.990
19:48800242:C:G	R119P	0.990
19:48800288:C:G	G104R	0.990
19:48806646:A:C	F57L	0.990
19:48806646:A:T	F57L	0.990
19:48806648:A:G	F57L	0.990
19:48797271:A:T	L253H	0.989
19:48799684:T:G	K229T	0.989

dbSNP variants (sampled 300 via entrez): RS1000190716 (19:48803206 A>G), RS1000313333 (19:48800964 GCA>G), RS1000314372 (19:48796166 A>T), RS1000433484 (19:48797563 T>C), RS1000598893 (19:48801839 G>A), RS1000667124 (19:48803415 C>A), RS1000768345 (19:48796294 G>A,T), RS1000919445 (19:48801693 A>C), RS1001045343 (19:48805596 T>A,C), RS1001130113 (19:48808084 G>A), RS1001202215 (19:48796655 C>A,T), RS1001291049 (19:48811697 C>A), RS1001692867 (19:48802680 T>C), RS1001844336 (19:48810560 G>A), RS1001873175 (19:48808023 G>A)

Disease associations

OMIM: gene MIM:113530 | disease phenotypes: MIM:618850

GenCC curated gene-disease

Disease	Classification	Inheritance
hypervalinemia and hyperleucine-isoleucinemia	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hypervalinemia and hyperleucine-isoleucinemia	Definitive	AR

Mondo (2): hypervalinemia and hyperleucine-isoleucinemia (MONDO:0100058), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001348	Brisk reflexes
HP:0002315	Headache
HP:0002922	Increased CSF protein concentration
HP:0010910	Hypervalinemia
HP:0010911	Hyperleucinemia
HP:0010913	Hyperisoleucinemia
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0031993	Hoffmann sign

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST002422_1	Alzheimer’s disease	9.000000e-116
GCST004069_9	Cerebrospinal fluid AB1-42 levels	5.000000e-94
GCST004523_5	Resting metabolic rate	5.000000e-06
GCST004584_2	Waist-to-hip circumference ratio (smoking years interaction)	4.000000e-06
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST006256_2	Long-term memory (delayed word recall task)	4.000000e-07
GCST006585_8	Blood protein levels	1.000000e-12
GCST006612_1	LDL cholesterol	1.000000e-300
GCST006990_2	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	3.000000e-07
GCST006993_15	Hippocampal volume in Alzheimer’s disease dementia	8.000000e-07
GCST006996_4	Cerebrospinal AB1-42 levels in mild cognitive impairment	6.000000e-27
GCST006997_3	Cerebrospinal fluid t-tau levels in mild cognitive impairment	1.000000e-13
GCST006998_7	Cerebrospinal fluid p-tau levels in mild cognitive impairment	2.000000e-11
GCST007001_15	Cerebrospinal AB1-42 levels in normal cognition	9.000000e-11
GCST007007_4	Cerebrospinal fluid t-tau levels	1.000000e-20
GCST007008_6	Cerebrospinal fluid p-tau levels	3.000000e-18
GCST007009_7	Hippocampal volume	2.000000e-19
GCST007010_3	Logical memory (delayed recall)	2.000000e-18
GCST007011_3	Logical memory (immediate recall)	2.000000e-13
GCST007012_6	Cerebrospinal fluid AB1-42 levels	1.000000e-51
GCST007320_100	Alzheimer’s disease or family history of Alzheimer’s disease	2.000000e-143
GCST007320_40	Alzheimer’s disease or family history of Alzheimer’s disease	3.000000e-13
GCST007320_47	Alzheimer’s disease or family history of Alzheimer’s disease	6.000000e-12
GCST007320_78	Alzheimer’s disease or family history of Alzheimer’s disease	8.000000e-11
GCST007600_1	Alzheimer’s disease	3.000000e-14
GCST007600_2	Alzheimer’s disease	7.000000e-14
GCST007600_90	Alzheimer’s disease	1.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0008004	resting metabolic rate measurement
EFO:0004343	waist-hip ratio
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006805	word list delayed recall measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005035	hippocampal volume
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement
EFO:0004874	memory performance
EFO:0009268	family history of Alzheimer’s disease
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3616354 (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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
BAY-069	Inhibition	6.82	pIC50
compound 27 [PMID: 26938474]	Inhibition	6.7	pIC50
compound 42 [PMID: 26938474]	Inhibition	5.8	pIC50

ChEMBL bioactivities

131 potent at pChembl≥5 of 164 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	CHEMBL3617086
7.90	IC50	12.59	nM	CHEMBL3617084
7.90	IC50	12.59	nM	CHEMBL3617083
7.80	IC50	15.85	nM	CHEMBL3617085
7.80	IC50	15.85	nM	CHEMBL3617082
7.70	IC50	19.95	nM	CHEMBL3617080
7.60	IC50	25.12	nM	CHEMBL3617095
7.60	IC50	25.12	nM	CHEMBL3617079
7.50	IC50	31.62	nM	CHEMBL3617102
7.50	IC50	31.62	nM	CHEMBL3617085
7.40	IC50	39.81	nM	CHEMBL3617098
7.30	IC50	50.12	nM	CHEMBL3617078
7.30	IC50	50.12	nM	CHEMBL3617077
7.30	IC50	50.12	nM	CHEMBL3617083
7.30	IC50	50.12	nM	CHEMBL3617084
7.30	IC50	50.12	nM	CHEMBL3808902
7.30	IC50	50.12	nM	CHEMBL3809839
7.20	IC50	63.1	nM	CHEMBL3617080
7.20	IC50	63.1	nM	CHEMBL3617086
7.20	IC50	63.1	nM	CHEMBL3808971
7.20	IC50	63.1	nM	CHEMBL3809839
7.10	IC50	79.43	nM	CHEMBL3617094
7.10	IC50	79.43	nM	CHEMBL3617082
7.10	IC50	79.43	nM	CHEMBL3810317
7.00	IC50	100	nM	CHEMBL3617096
7.00	IC50	100	nM	CHEMBL3809282
7.00	IC50	100	nM	CHEMBL3808902
7.00	IC50	100	nM	CHEMBL3810317
6.90	IC50	125.9	nM	CHEMBL3617100
6.89	IC50	130	nM	BAY-069
6.82	IC50	153	nM	BAY-069
6.82	IC50	150	nM	CHEMBL5219436
6.80	IC50	158.5	nM	CHEMBL3617075
6.80	IC50	158.5	nM	CHEMBL3617078
6.80	IC50	158.5	nM	CHEMBL3617079
6.80	IC50	158.5	nM	CHEMBL3809237
6.79	IC50	162	nM	CHEMBL5220178
6.70	IC50	199.5	nM	CHEMBL3617105
6.70	IC50	199.5	nM	CHEMBL3617071
6.70	IC50	199.5	nM	CHEMBL3617098
6.70	IC50	199.5	nM	CHEMBL3794222
6.70	IC50	200	nM	CHEMBL5219436
6.60	IC50	251.2	nM	CHEMBL3617106
6.60	IC50	251.2	nM	CHEMBL3617103
6.60	IC50	251.2	nM	CHEMBL3617099
6.60	IC50	251.2	nM	CHEMBL3617070
6.60	IC50	251.2	nM	CHEMBL3617095
6.60	IC50	251.2	nM	CHEMBL3794419
6.60	IC50	251.2	nM	CHEMBL3809321
6.60	IC50	251.2	nM	CHEMBL3809916

PubChem BioAssay actives

129 with measured affinity, of 198 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
2-[(4-bromo-2,6-difluorophenyl)methylamino]-5-butyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0100	uM
2-[(4-bromo-2-fluorophenyl)methylamino]-5-butyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0126	uM
2-[[(1R)-1-(4-bromo-2-fluorophenyl)ethyl]amino]-5-butyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0126	uM
5-butyl-2-[(4-chloro-2-fluorophenyl)methylamino]-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0158	uM
5-butyl-2-[(4-chloro-2,6-difluorophenyl)methylamino]-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0158	uM
2-[[(1R)-1-(4-bromo-2-fluorophenyl)ethyl]amino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0199	uM
2-[(4-bromo-2-fluorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0251	uM
2-[(4-bromophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0251	uM
2-[(4-chlorophenyl)methylamino]-5-(furan-3-ylmethyl)-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0316	uM
5-butyl-2-[(4-chlorophenyl)methylamino]-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0398	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.0501	uM
2-[(4-chloro-2-fluorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0501	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-phenylbenzimidazole-5-carboxamide	1303047: Inhibition of BCATm in differentiated primary human adipocytes using L-Serine and L-Leucine as substrate after overnight incubation by reverse-phase HPLC method	ic50	0.0501	uM
2-[(4-chloro-2,6-difluorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0501	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.0631	uM
2-[(4-chlorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.0794	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-thiophen-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.0794	uM
5-benzyl-2-[(4-chlorophenyl)methylamino]-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.1000	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-thiophen-3-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.1000	uM
2-[(4-chlorophenyl)methylamino]-5-(3-methylbutyl)-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.1259	uM
3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-[difluoro(phenyl)methyl]-1H-pyrimidine-2,4-dione	1918060: Inhibition of human recombinant BCAT2 using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1500	uM
3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione	1918060: Inhibition of human recombinant BCAT2 using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1530	uM
2-[(5-bromo-2-pyridinyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.1585	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-(2-methylsulfanylphenyl)benzimidazole-5-carboxamide	1303047: Inhibition of BCATm in differentiated primary human adipocytes using L-Serine and L-Leucine as substrate after overnight incubation by reverse-phase HPLC method	ic50	0.1585	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-5-methoxy-2-(2-methylphenoxy)benzonitrile	1918060: Inhibition of human recombinant BCAT2 using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.1620	uM
5-methyl-4-oxo-N-(1,3,4-thiadiazol-2-yl)-3H-thieno[2,3-d]pyrimidine-6-carboxamide	1293675: Inhibition of human BCATm incubated for 10 mins by Amplex red- based fluorescence analysis	ic50	0.1995	uM
2-[(4-chloro-3-methylphenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.1995	uM
2-[(4-chlorophenoxy)methyl]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.1995	uM
2-[(4-methylphenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.2512	uM
2-[(4-chlorophenyl)methylamino]-5-(2-methylpropyl)-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.2512	uM
2-[2-(4-chlorophenyl)ethylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.2512	uM
2-[(4-chlorophenyl)methoxy]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.2512	uM
1-[(1R,3S)-3-[(5-cyanothiophene-2-carbonyl)amino]cyclohexyl]-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.2512	uM
1-[(1R,3S)-3-[(5-chlorothiophene-2-carbonyl)amino]cyclohexyl]-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.2512	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-cyclopropyl-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.2512	uM
2-(3,6,7-trimethylquinolin-2-yl)sulfanylacetic acid	1293675: Inhibition of human BCATm incubated for 10 mins by Amplex red- based fluorescence analysis	ic50	0.2512	uM
4-[2,4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]-2-(2-methylphenoxy)naphthalene-1-carbonitrile	1918060: Inhibition of human recombinant BCAT2 using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay	ic50	0.2700	uM
2-[(4-chloro-3-fluorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.3162	uM
7-oxo-2-(2-oxo-2-pyrrolidin-1-ylethyl)-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.5012	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-2-pyridin-3-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.5012	uM
2-[(4-chloro-2-methoxyphenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.6310	uM
2-[2-(4-chlorophenyl)ethyl]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.6310	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-(2-methyl-1,3-thiazol-4-yl)benzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.6310	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-propan-2-yl-2-pyridin-2-ylbenzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.6310	uM
2-[(4-bromophenyl)methylamino]-5-propyl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.6310	uM
N-(4-chlorophenyl)-3-cyano-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-2-carboxamide	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	0.7943	uM
1-[(1R,3S)-3-[(5-bromothiophene-2-carbonyl)amino]cyclohexyl]-N-methyl-2-(1,3-thiazol-2-yl)benzimidazole-5-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	0.7943	uM
2-[2-[(5-methyl-4-oxo-3H-thieno[2,3-d]pyrimidine-6-carbonyl)amino]phenyl]acetic acid	1293675: Inhibition of human BCATm incubated for 10 mins by Amplex red- based fluorescence analysis	ic50	1.0000	uM
4-chloro-N-(3-cyano-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidin-2-yl)benzamide	1246070: Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	ic50	1.0000	uM
5-bromo-N-[(1S,3R)-3-(2-pyridin-2-ylbenzimidazol-1-yl)cyclohexyl]thiophene-2-carboxamide	1303046: Inhibition of human BCATm (28 to 392 residues) using L-Leucine and alpha-ketogluterate as substrate assessed as L-glutamate production after 10 mins by Amplex red dye based L-GOx and HRP enzyme coupled assay	ic50	1.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Cidofovir	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Clodronic Acid	increases expression	1
Doxorubicin	decreases expression	1
Haloperidol	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3618962	Binding	Inhibition of human cloned BCATm expressed in Escherichia coli BL21 DE3 assessed as L-glutamate production from alpha-ketoglutarate after 10 mins by fluorescent assay	The Discovery of in Vivo Active Mitochondrial Branched-Chain Aminotransferase (BCATm) Inhibitors by Hybridizing Fragment and HTS Hits. — 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_D1LP	Abcam K-562 BCAT2 KO	Cancer cell line	Female
CVCL_D2IA	Abcam Raji BCAT2 KO	Cancer cell line	Male
CVCL_UQ21	Abcam Jurkat BCAT2 KO	Cancer cell line	Male
CVCL_XL97	HAP1 BCAT2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery