KYAT3

Summary

KYAT3 (kynurenine aminotransferase 3, HGNC:33238) is a protein-coding gene on chromosome 1p22.2, encoding Kynurenine–oxoglutarate transaminase 3 (Q6YP21). Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA), an intermediate in the tryptophan catabolic pathway which is also a broad spectrum antagonist of the three ionotropic excitatory amino acid receptors among others.

This gene encodes an aminotransferase that transaminates kynurenine to form kynurenic acid, which is a metabolite of tryptophan. Multiple alternatively spliced transcript variants that encode different proteins have been described for this gene. This gene shares 5’ exon structure with the RNA binding motif protein, X-linked-like 1 locus on chromosome 1, but the coding sequences are non-overlapping.

Source: NCBI Gene 56267 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_001008661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33238
Approved symbol	KYAT3
Name	kynurenine aminotransferase 3
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	RBM1, RP11-82K18.3, KAT3, KATIII
Ensembl gene	ENSG00000137944
Ensembl biotype	protein_coding
OMIM	610656
Entrez	56267

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000260508, ENST00000370486, ENST00000370491, ENST00000446900

RefSeq mRNA: 6 — MANE Select: NM_001008661 NM_001008661, NM_001008662, NM_001349447, NM_001349448, NM_001349449, NM_001349450

CCDS: CCDS30766, CCDS30767

Canonical transcript exons

ENST00000260508 — 14 exons

Exon	Start	End
ENSE00001691159	88992585	88992629
ENSE00001883763	88935779	88936245
ENSE00003461621	88949091	88949277
ENSE00003470546	88953063	88953152
ENSE00003545369	88955149	88955225
ENSE00003553998	88943350	88943423
ENSE00003558042	88943005	88943091
ENSE00003617730	88969409	88969467
ENSE00003621312	88961381	88961506
ENSE00003637394	88962059	88962145
ENSE00003651858	88964829	88964978
ENSE00003681487	88968670	88968814
ENSE00003688776	88988252	88988351
ENSE00003787314	88961167	88961287

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.6398 / max 48.3036, expressed in 1376 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13125	13.3929	1782
13127	9.2058	1772
13126	1.5192	969
13129	0.6965	460
13130	0.5038	302
13128	0.4241	244

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.01	gold quality
corpus epididymis	UBERON:0004359	94.14	gold quality
esophagus squamous epithelium	UBERON:0006920	94.02	gold quality
germinal epithelium of ovary	UBERON:0001304	93.80	gold quality
epithelium of esophagus	UBERON:0001976	93.55	gold quality
oral cavity	UBERON:0000167	93.47	gold quality
adrenal tissue	UBERON:0018303	93.35	gold quality
squamous epithelium	UBERON:0006914	93.24	gold quality
palpebral conjunctiva	UBERON:0001812	93.20	gold quality
gingival epithelium	UBERON:0001949	92.97	gold quality
cauda epididymis	UBERON:0004360	92.95	gold quality
gingiva	UBERON:0001828	92.91	gold quality
caput epididymis	UBERON:0004358	92.88	gold quality
upper leg skin	UBERON:0004262	92.69	gold quality
cervix epithelium	UBERON:0004801	92.07	gold quality
pigmented layer of retina	UBERON:0001782	91.93	gold quality
cartilage tissue	UBERON:0002418	91.89	gold quality
oviduct epithelium	UBERON:0004804	91.79	gold quality
seminal vesicle	UBERON:0000998	91.75	gold quality
colonic mucosa	UBERON:0000317	91.71	gold quality
tongue squamous epithelium	UBERON:0006919	91.71	gold quality
parietal pleura	UBERON:0002400	91.69	gold quality
epithelium of mammary gland	UBERON:0003244	91.69	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.69	gold quality
cervix squamous epithelium	UBERON:0006922	91.69	gold quality
mammary duct	UBERON:0001765	91.65	gold quality
mammalian vulva	UBERON:0000997	91.62	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.62	gold quality
nasal cavity mucosa	UBERON:0001826	91.56	gold quality
nephron tubule	UBERON:0001231	91.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.81
E-GEOD-124858	no	240.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting KYAT3, 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-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-337-3P	97.90	69.37	1052
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-345-5P	96.40	66.43	663
HSA-MIR-1258	96.08	67.74	700

Literature-anchored findings (GeneRIF, showing 5)

• Using shotgun mass spectrometry, it was found that this protein is differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• The haplotype of KAT III gene CGCTCT may have effect on the function of this enzyme in formation of kynurenic acid in some patients with major depressive episodes. (PMID:21492941)
• human KAT III/CCBL2 possesses cysteine S-conjugate beta-lyase activity, as does mouse KAT II (PMID:25231977)
• Immunohistochemical analysis revealed the presence of KAT I, II, and III in all examined corneal sections. (PMID:28706436)
• Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients. (PMID:35771747)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	kyat3.1	ENSDARG00000100818
danio_rerio	kyat3.2	ENSDARG00000101791
danio_rerio	kyat3.3	ENSDARG00000102243
		ENSDARG00000102423
mus_musculus	Kyat3	ENSMUSG00000040213
rattus_norvegicus	Kyat3	ENSRNOG00000043426
drosophila_melanogaster	Kyat	FBGN0037955
caenorhabditis_elegans		WBGENE00009232
caenorhabditis_elegans		WBGENE00010984

Paralogs (7): AADAT (ENSG00000109576), ACCS (ENSG00000110455), GPT2 (ENSG00000166123), GPT (ENSG00000167701), KYAT1 (ENSG00000171097), TAT (ENSG00000198650), ACCSL (ENSG00000205126)

Protein

Protein identifiers

Kynurenine–oxoglutarate transaminase 3 — Q6YP21 (reviewed: Q6YP21)

Alternative names: Cysteine-S-conjugate beta-lyase 2, Kynurenine aminotransferase 3, Kynurenine aminotransferase III, Kynurenine–glyoxylate transaminase, Kynurenine–oxoglutarate transaminase III

All UniProt accessions (3): Q6YP21, A0A0A0MRN7, B4DW13

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA), an intermediate in the tryptophan catabolic pathway which is also a broad spectrum antagonist of the three ionotropic excitatory amino acid receptors among others. May catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond. Has transaminase activity towards L-kynurenine, tryptophan, phenylalanine, serine, cysteine, methionine, histidine, glutamine and asparagine with glyoxylate as an amino group acceptor (in vitro). Has lower activity with 2-oxoglutarate as amino group acceptor (in vitro).

Subunit / interactions. Homodimer.

Pathway. Amino-acid degradation; L-kynurenine degradation; kynurenate from L-kynurenine: step 1/2.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6YP21-1	1	yes
Q6YP21-2	2
Q6YP21-3	3

RefSeq proteins (6): NP_001008661, NP_001008662, NP_001336376, NP_001336377, NP_001336378, NP_001336379 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004839	Aminotransferase_I/II_large	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR051326	Kynurenine-oxoglutarate_AT	Family

Pfam: PF00155

Enzyme classification (BRENDA):

• EC 2.6.1.7 — kynurenine-oxoglutarate transaminase (BRENDA: 24 organisms, 197 substrates, 229 inhibitors, 160 Km, 93 kcat entries)
• EC 4.4.1.13 — cysteine-S-conjugate beta-lyase (BRENDA: 60 organisms, 215 substrates, 105 inhibitors, 118 Km, 41 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-CYSTATHIONINE	0.04–15	45
L-KYNURENINE	0.083–27	28
2-OXOGLUTARATE	0.013–8.1	15
PYRUVATE	0.0175–12.1	12
CYSTATHIONINE	0.02–4.2	9
L-DJENKOLATE	0.033–3.6	9
L-3-HYDROXYKYNURENINE	1.36–6.3	6
2-OXOBUTYRATE	0.0002–42.2	5
L-METHIONINE	0.9–6.4	5
L-TRYPTOPHAN	1.2–12.9	5
PHENYLPYRUVATE	0.6–1.8	5
L-CYSTEINE	0.29–11.5	5
L-CYSTINE	0.0812–5.4	5
2-OXO-4-METHYLTHIOBUTYRATE	0.0024–5.7	4
GLYOXYLATE	0.4–18	4

Catalyzed reactions (Rhea), 4 shown:

• an S-substituted L-cysteine + H2O = a thiol + pyruvate + NH4(+) (RHEA:18121)
• L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + H2O (RHEA:65560)
• L-kynurenine + glyoxylate = kynurenate + glycine + H2O (RHEA:65896)
• 3-hydroxy-L-kynurenine + glyoxylate = xanthurenate + glycine + H2O (RHEA:65900)

UniProt features (14 total): modified residue 4, binding site 3, splice variant 3, chain 1, sequence variant 1, sequence conflict 1, initiator methionine 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6YP21-F1	91.60	0.82

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 (3): 71; 218; 429

Post-translational modifications (4): 2, 116, 116, 280

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-71240	Tryptophan catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 144 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, REACTOME_TRYPTOPHAN_CATABOLISM, GOBP_KETONE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, DAZARD_RESPONSE_TO_UV_SCC_UP, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_BENZENE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_AMINO_ACID_CATABOLIC_PROCESS, GOBP_2_OXOGLUTARATE_METABOLIC_PROCESS, chr1p22, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GARY_CD5_TARGETS_UP

GO Biological Process (5): 2-oxoglutarate metabolic process (GO:0006103), amino acid metabolic process (GO:0006520), obsolete kynurenine metabolic process (GO:0070189), obsolete L-kynurenine catabolic process (GO:0097053), biosynthetic process (GO:0009058)

GO Molecular Function (9): RNA binding (GO:0003723), L-kynurenine:2-oxoglutarate transaminase activity (GO:0016212), pyridoxal phosphate binding (GO:0030170), protein homodimerization activity (GO:0042803), L-kynurenine:glyoxylate transaminase activity (GO:0047315), cysteine-S-conjugate beta-lyase activity (GO:0047804), transaminase activity (GO:0008483), transferase activity (GO:0016740), lyase activity (GO:0016829)

GO Cellular Component (2): cytoplasm (GO:0005737), mitochondrion (GO:0005739)

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
transaminase activity	2
catalytic activity	2
dicarboxylic acid metabolic process	1
primary metabolic process	1
metabolic process	1
nucleic acid binding	1
anion binding	1
vitamin B6 binding	1
identical protein binding	1
protein dimerization activity	1
carbon-sulfur lyase activity	1
transferase activity, transferring nitrogenous groups	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KYAT3	GOT2	P00505	768
KYAT3	KMO	O15229	746
KYAT3	KYNU	Q16719	709
KYAT3	AFMID	Q63HM1	654
KYAT3	TDO2	P48775	638
KYAT3	HAAO	P46952	613
KYAT3	QPRT	Q15274	599
KYAT3	GPR35	Q9HC97	553
KYAT3	GCSH	P23434	548
KYAT3	AADAT	Q8N5Z0	541
KYAT3	ACMSD	Q8TDX5	496
KYAT3	IDO1	P14902	491
KYAT3	ALDH4A1	P30038	482
KYAT3	LYRM2	Q9NU23	462
KYAT3	IDO2	Q6ZQW0	456

IntAct

19 interactions, top by confidence:

A	B	Type	Score
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
TRUB2	NME6	psi-mi:“MI:0914”(association)	0.350
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
MAP1LC3B		psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
RNF7	SOCS2	psi-mi:“MI:0914”(association)	0.350
LRRC46	GTPBP6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
SLC17A1	SGTA	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
KYAT3	RABIF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (48): CCBL2 (Affinity Capture-RNA), CCBL2 (Affinity Capture-RNA), CCBL2 (Affinity Capture-RNA), CCBL2 (Co-fractionation), CCBL2 (Co-fractionation), PGM1 (Co-fractionation), PGM5 (Co-fractionation), CCBL2 (Affinity Capture-MS), CCBL2 (Affinity Capture-MS), CCBL2 (Affinity Capture-RNA), CCBL2 (Affinity Capture-MS), CCBL2 (Synthetic Lethality), CCBL2 (Co-fractionation), CCBL2 (Co-fractionation), CCBL2 (Co-fractionation)

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

Diamond homologs: A1ADA5, A1VDD3, A3PMF8, A4QAL4, A7ZP71, A8A2C0, A9N5B4, B1I544, B1IXT4, B1X8W6, B2A250, B4SYW9, B4TBG4, B4TPI0, B5BCP8, B5EZH6, B5FNT7, B5R270, B5RCC2, B6I7J6, B7LAR8, B7LM78, B7M5T5, B7MG20, B7MXT4, B7N5L8, B7NNT2, B7UFR5, B8DJJ6, C0Q071, C4ZU95, C6BUK3, C6C2Z3, E9L7A5, H3ZPU1, O31665, O33822, O58489, O67781, O86459

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	5	27.5×	1e-04
Neddylation	5	11.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	5	65.0×	1e-06
mitophagy	5	58.9×	1e-06
autophagosome assembly	5	41.6×	6e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2737 predictions. Top by Δscore:

Variant	Effect	Δscore
1:88942998:AACTT:A	donor_loss	1.0000
1:88942999:ACTT:A	donor_loss	1.0000
1:88943000:CTT:C	donor_loss	1.0000
1:88943001:TTA:T	donor_loss	1.0000
1:88943003:A:AC	donor_gain	1.0000
1:88943003:AC:A	donor_loss	1.0000
1:88943004:C:CC	donor_gain	1.0000
1:88943087:AGTTT:A	acceptor_gain	1.0000
1:88943088:GTTT:G	acceptor_gain	1.0000
1:88943089:TTT:T	acceptor_gain	1.0000
1:88943090:TT:T	acceptor_gain	1.0000
1:88943091:TCTGA:T	acceptor_loss	1.0000
1:88943092:C:CC	acceptor_gain	1.0000
1:88943092:C:CG	acceptor_loss	1.0000
1:88943093:T:A	acceptor_loss	1.0000
1:88950377:AG:A	donor_gain	1.0000
1:88953148:CCAAG:C	acceptor_gain	1.0000
1:88953149:CAAG:C	acceptor_gain	1.0000
1:88953149:CAAGC:C	acceptor_gain	1.0000
1:88955221:AGTAG:A	acceptor_gain	1.0000
1:88955222:GTAG:G	acceptor_gain	1.0000
1:88955223:TAG:T	acceptor_gain	1.0000
1:88962057:A:AC	donor_gain	1.0000
1:88962058:C:CC	donor_gain	1.0000
1:88962058:CAGAT:C	donor_gain	1.0000
1:88964823:ACTT:A	donor_loss	1.0000
1:88964824:CTT:C	donor_loss	1.0000
1:88964825:TTA:T	donor_loss	1.0000
1:88964826:TAC:T	donor_loss	1.0000
1:88964827:A:AC	donor_gain	1.0000

AlphaMissense

2987 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:88943005:T:A	K434N	0.998
1:88943005:T:G	K434N	0.998
1:88943014:G:C	C431W	0.998
1:88953146:A:G	W291R	0.998
1:88953146:A:T	W291R	0.998
1:88955154:A:G	W287R	0.998
1:88955154:A:T	W287R	0.998
1:88961218:C:G	D246H	0.998
1:88943006:T:A	K434I	0.997
1:88949116:G:C	F372L	0.997
1:88949116:G:T	F372L	0.997
1:88949118:A:G	F372L	0.997
1:88955182:A:C	S277R	0.997
1:88955182:A:T	S277R	0.997
1:88955184:T:G	S277R	0.997
1:88961217:T:A	D246V	0.997
1:88961217:T:G	D246A	0.997
1:88961246:G:C	C236W	0.997
1:88961393:G:C	N218K	0.997
1:88961393:G:T	N218K	0.997
1:88943015:C:T	C431Y	0.996
1:88943021:C:G	R429P	0.996
1:88955156:C:T	G286D	0.996
1:88961217:T:C	D246G	0.996
1:88961218:C:A	D246Y	0.996
1:88961227:A:G	C243R	0.996
1:88962116:G:C	C161W	0.996
1:88968814:C:A	W53C	0.996
1:88968814:C:G	W53C	0.996
1:88969410:A:G	W53R	0.996

dbSNP variants (sampled 300 via entrez): RS1000016600 (1:88954933 T>A), RS1000087935 (1:88956547 C>T), RS1000128092 (1:88953351 C>A,G), RS1000179640 (1:88935819 A>G), RS1000180404 (1:88939077 T>C), RS1000241856 (1:88959448 C>T), RS1000293703 (1:88945375 A>G), RS1000358940 (1:88924087 A>C), RS1000385411 (1:88932331 T>C,G), RS1000535484 (1:88977437 G>A), RS1000541919 (1:88927213 A>G,T), RS1000557682 (1:88955282 T>C), RS1000608555 (1:88972084 T>C), RS1000650906 (1:88987312 G>A), RS1000655115 (1:88927042 C>T)

Disease associations

OMIM: gene MIM:610656 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001277_8	Liver enzyme levels (gamma-glutamyl transferase)	4.000000e-11
GCST007611_10	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	3.000000e-12
GCST008062_117	Blood urea nitrogen levels	2.000000e-08
GCST009733_24	Urinary metabolite levels in chronic kidney disease	6.000000e-13
GCST012020_232	Serum metabolite levels	2.000000e-69
GCST90020029_1369	Waist circumference adjusted for body mass index	2.000000e-11
GCST90020029_1370	Waist circumference adjusted for body mass index	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0005116	urinary metabolite measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2046260 (SINGLE PROTEIN)

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 7 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.82	Kd	15.12	nM	CHEMBL5653589
7.79	ED50	16.09	nM	CHEMBL5653589
5.91	IC50	1230	nM	CHEMBL2321944
5.19	IC50	6400	nM	CHEMBL2049092
5.04	IC50	9040	nM	CHEMBL2047851

PubChem BioAssay actives

4 with measured affinity, of 11 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148007: Binding affinity to human CCBL2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0151	uM
(3S)-3-amino-1-hydroxy-6-phenoxy-3,4-dihydroquinolin-2-one	727186: Inhibition of human KAT3 using L-kynurenine as substrate measured after 24 hrs by SpectraMax plate reader analysis	ic50	1.2300	uM
(3S)-3-amino-1-hydroxy-7-methoxy-3,4-dihydroquinolin-2-one	727186: Inhibition of human KAT3 using L-kynurenine as substrate measured after 24 hrs by SpectraMax plate reader analysis	ic50	6.4000	uM
(3S)-3-amino-1-hydroxy-3,4-dihydroquinolin-2-one	727186: Inhibition of human KAT3 using L-kynurenine as substrate measured after 24 hrs by SpectraMax plate reader analysis	ic50	9.0400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	affects response to substance	1
Air Pollutants	decreases expression	1
Antimycin A	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2050769	Binding	Inhibition of human KAT3	Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia. — ACS Med Chem Lett
CHEMBL3821392	ADMET	Binding affinity to CCBL2 in human HepG2 assessed as intensity fold change of cumulated normalized intensity of protein between capture and competition assay at 100 uM after 1 hr in presence of active Tcp-CC-13 by differential competition c	Identification of Potential Off-target Toxicity Liabilities of Catechol-O-methyltransferase Inhibitors by Differential Competition Capture Compound Mass Spectrometry. — J Med Chem

Clinical trials (associated diseases)

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