AADAT

Summary

AADAT (aminoadipate aminotransferase, HGNC:17929) is a protein-coding gene on chromosome 4q33, encoding Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (Q8N5Z0). Transaminase with broad substrate specificity.

This gene encodes a protein that is highly similar to mouse and rat kynurenine aminotransferase II. The rat protein is a homodimer with two transaminase activities. One activity is the transamination of alpha-aminoadipic acid, a final step in the saccaropine pathway which is the major pathway for L-lysine catabolism. The other activity involves the transamination of kynurenine to produce kynurenine acid, the precursor of kynurenic acid which has neuroprotective properties. Several transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 51166 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 75 total — 31 pathogenic, 2 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_016228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17929
Approved symbol	AADAT
Name	aminoadipate aminotransferase
Location	4q33
Locus type	gene with protein product
Status	Approved
Aliases	KATII, KAT2, KYAT2
Ensembl gene	ENSG00000109576
Ensembl biotype	protein_coding
OMIM	611754
Entrez	51166

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 retained_intron

ENST00000337664, ENST00000353187, ENST00000502392, ENST00000505906, ENST00000507375, ENST00000509167, ENST00000510340, ENST00000515480, ENST00000883571, ENST00000883572, ENST00000883573, ENST00000918894, ENST00000918895, ENST00000969295

RefSeq mRNA: 4 — MANE Select: NM_016228 NM_001286682, NM_001286683, NM_016228, NM_182662

CCDS: CCDS3814, CCDS75209

Canonical transcript exons

ENST00000337664 — 13 exons

Exon	Start	End
ENSE00000970552	170088396	170088564
ENSE00000970555	170070587	170070652
ENSE00000970556	170069148	170069230
ENSE00000970557	170068591	170068687
ENSE00000970558	170067327	170067388
ENSE00000970559	170066414	170066478
ENSE00001139501	170060222	170060969
ENSE00001151616	170061892	170061993
ENSE00001151624	170064719	170064825
ENSE00001354788	170089624	170089956
ENSE00003565250	170073136	170073345
ENSE00003640121	170078509	170078583
ENSE00003693292	170087116	170087248

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 89.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.2680 / max 45.1680, expressed in 1309 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54829	3.3131	1222
54828	0.8402	544
54827	0.1091	24
54830	0.0056	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	89.98	gold quality
liver	UBERON:0002107	88.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.79	gold quality
body of uterus	UBERON:0009853	85.30	gold quality
endocervix	UBERON:0000458	84.56	gold quality
ganglionic eminence	UBERON:0004023	83.95	gold quality
cortical plate	UBERON:0005343	83.82	gold quality
ventricular zone	UBERON:0003053	83.68	gold quality
right coronary artery	UBERON:0001625	83.34	gold quality
endometrium	UBERON:0001295	83.21	gold quality
smooth muscle tissue	UBERON:0001135	83.16	gold quality
body of pancreas	UBERON:0001150	82.73	gold quality
amygdala	UBERON:0001876	82.55	gold quality
right uterine tube	UBERON:0001302	82.33	gold quality
tibial nerve	UBERON:0001323	82.30	gold quality
ectocervix	UBERON:0012249	82.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.02	gold quality
anterior cingulate cortex	UBERON:0009835	82.00	gold quality
stromal cell of endometrium	CL:0002255	81.97	gold quality
popliteal artery	UBERON:0002250	81.85	gold quality
tibial artery	UBERON:0007610	81.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.83	gold quality
uterus	UBERON:0000995	81.78	gold quality
prefrontal cortex	UBERON:0000451	81.77	gold quality
thoracic aorta	UBERON:0001515	81.71	gold quality
aorta	UBERON:0000947	81.70	gold quality
ascending aorta	UBERON:0001496	81.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.64	gold quality
right frontal lobe	UBERON:0002810	81.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting AADAT, 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-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-6727-3P	99.49	65.92	1333

Literature-anchored findings (GeneRIF, showing 12)

• A human cDNA encodes a 425-residue protein with a mitochondrial cleavage signal and a pyridoxal-phosphate binding site, ~70% identical to the mouse and rat AADAT orthologs. Bacterial expression studies confirm that the gene encodes AADAT activity. (PMID:12126930)
• analysis of the crystal structure of kynurenine aminotransferase II (PMID:18056995)
• analysis of the crystal structure of human kynurenine aminotransferase II (PMID:18056996)
• association of SNP AADAT+401C/T with the host immune response to bacterial meningitis, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site (PMID:21473761)
• Somatization is characterized by disorders in kynurenine aminotransferase activity and an increased neurotoxic potential (PMID:21712776)
• Participants with major depression had lower levels of kynurenine compared to controls, with intermediate concentrations in somatoform patients. (PMID:24140252)
• he optimised method of protein production provides a fast and reliable technique to generate large quantities of active human KAT2 suitable for future small-molecule lead compound screening and structural design work. (PMID:26773745)
• Immunohistochemical analysis revealed the presence of KAT I, II, and III in all examined corneal sections. (PMID:28706436)
• In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls. We genotyped, by using TaqMan probes, four polymorphism. (PMID:29777939)
• The free thyroxine(FT4)-associated variant rs6854291-influences transcript levels of kynurenine/alpha-aminoadipate aminotransferase (AADAT) in thyroid, implicating AADAT as the causal gene underlying the FT4 association at this locus. AADAT-rs6854291 is associated with both the 3,3’,5-triiodothyronine (T3) levels and T3/T4 ratio. (PMID:30367059)
• N-Acetylcysteine Inhibits Kynurenine Aminotransferase II. (PMID:32768617)
• Expression analysis of selected genes involved in tryptophan metabolic pathways in Egyptian children with Autism Spectrum Disorder and learning disabilities. (PMID:33767242)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	aadat	ENSDARG00000011410
mus_musculus	Aadat	ENSMUSG00000057228
rattus_norvegicus	Aadat	ENSRNOG00000011861

Paralogs (7): ACCS (ENSG00000110455), KYAT3 (ENSG00000137944), GPT2 (ENSG00000166123), GPT (ENSG00000167701), KYAT1 (ENSG00000171097), TAT (ENSG00000198650), ACCSL (ENSG00000205126)

Protein

Protein identifiers

Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial — Q8N5Z0 (reviewed: Q8N5Z0)

Alternative names: 2-aminoadipate aminotransferase, 2-aminoadipate transaminase, Alpha-aminoadipate aminotransferase, Glycine transaminase AADAT, Kynurenine aminotransferase II, Kynurenine–glyoxylate transaminase AADAT, Kynurenine–oxoglutarate aminotransferase II, Kynurenine–oxoglutarate transaminase 2, Kynurenine–oxoglutarate transaminase II, Methionine–glyoxylate transaminase AADAT

All UniProt accessions (5): Q8N5Z0, D6RC56, D6REB9, D6RFY7, Q4W5N8

UniProt curated annotations — full annotation on UniProt →

Function. Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion.

Tissue specificity. Higher expression in the liver. Also found in heart, brain, kidney, pancreas, prostate, testis and ovary.

Activity regulation. Kynurenine transaminase activity is competitively inhibited by aminoadipate, asparagine, glutamate, histidine, cysteine, lysine, 3-hydroxy-kynurenine and phenylalanine.

Pathway. Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 4/6.

Miscellaneous. May be due to a competing donor splice site.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5Z0-1	1	yes
Q8N5Z0-2	2

RefSeq proteins (4): NP_001273611, NP_001273612, NP_057312, NP_872603 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004839	Aminotransferase_I/II_large	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR050859	Class-I_PLP-dep_aminotransf	Family

Pfam: PF00155

Enzyme classification (BRENDA):

• EC 2.6.1.39 — 2-aminoadipate transaminase (BRENDA: 7 organisms, 41 substrates, 21 inhibitors, 47 Km, 20 kcat entries)
• EC 2.6.1.7 — kynurenine-oxoglutarate transaminase (BRENDA: 24 organisms, 197 substrates, 229 inhibitors, 160 Km, 93 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-KYNURENINE	0.083–27	28
2-OXOGLUTARATE	0.013–8.1	15
PYRUVATE	0.0175–12.1	12
2-OXOGLUTARATE	0.27–3.6	11
L-2-AMINOADIPATE	0.02–20	8
2-OXOADIPATE	0.01–2.5	6
L-GLUTAMATE	0.46–250	6
L-3-HYDROXYKYNURENINE	1.36–6.3	6
2-OXOISOCAPROATE	0.0288–0.43	5
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-LEUCINE	0.2–0.95	4
2-OXO-4-METHYLTHIOBUTYRATE	0.0024–5.7	4

Catalyzed reactions (Rhea), 12 shown:

• L-2-aminoadipate + 2-oxoglutarate = 2-oxoadipate + L-glutamate (RHEA:12601)
• glycine + 2-oxoglutarate = glyoxylate + L-glutamate (RHEA:14089)
• glyoxylate + L-methionine = 4-methylsulfanyl-2-oxobutanoate + glycine (RHEA:22884)
• 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)
• 2-oxobutanoate + L-kynurenine = (2S)-2-aminobutanoate + kynurenate + H2O (RHEA:66044)
• indole-3-pyruvate + L-kynurenine = kynurenate + L-tryptophan + H2O (RHEA:66052)
• 2-oxohexanoate + L-kynurenine = L-2-aminohexanoate + kynurenate + H2O (RHEA:66060)
• 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O (RHEA:66068)
• 2-oxopentanoate + L-kynurenine = L-2-aminopentanoate + kynurenate + H2O (RHEA:66076)
• 3-phenylpyruvate + L-kynurenine = kynurenate + L-phenylalanine + H2O (RHEA:66092)

UniProt features (72 total): helix 21, strand 18, modified residue 10, turn 10, binding site 5, sequence conflict 2, transit peptide 1, chain 1, splice variant 1, region of interest 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6D0A	X-RAY DIFFRACTION	1.47
5TF5	X-RAY DIFFRACTION	1.81
5EUN	X-RAY DIFFRACTION	1.82
5EFS	X-RAY DIFFRACTION	1.83
2R2N	X-RAY DIFFRACTION	1.95
6T8P	X-RAY DIFFRACTION	2.02
2XH1	X-RAY DIFFRACTION	2.1
4GE7	X-RAY DIFFRACTION	2.1
4GEB	X-RAY DIFFRACTION	2.15
2QLR	X-RAY DIFFRACTION	2.3
2VGZ	X-RAY DIFFRACTION	2.3
4GE4	X-RAY DIFFRACTION	2.41
4GE9	X-RAY DIFFRACTION	2.43
3DC1	X-RAY DIFFRACTION	2.5
6T8Q	X-RAY DIFFRACTION	2.51
4GDY	X-RAY DIFFRACTION	2.89
3UE8	X-RAY DIFFRACTION	3.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5Z0-F1	97.42	0.95

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 20; 74; 142; 202; 399

Post-translational modifications (10): 179, 263, 263, 263, 339, 339, 367, 367, 422, 69

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-71064	Lysine catabolism
R-HSA-71240	Tryptophan catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 96 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, REACTOME_TRYPTOPHAN_CATABOLISM, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, KEGG_LYSINE_DEGRADATION, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (6): 2-oxoglutarate metabolic process (GO:0006103), glutamate metabolic process (GO:0006536), obsolete L-lysine catabolic process to acetyl-CoA via L-saccharopine (GO:0033512), obsolete kynurenine metabolic process (GO:0070189), obsolete alpha-amino acid metabolic process (GO:1901605), biosynthetic process (GO:0009058)

GO Molecular Function (9): 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), L-2-aminoadipate:2-oxoglutarate transaminase activity (GO:0047536), glycine:2-oxoglutarate transaminase activity (GO:0047958), L-methionine:glyoxylate transaminase activity (GO:0050094), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	2
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transaminase activity	3
dicarboxylic acid metabolic process	2
amino acid metabolic process	1
metabolic process	1
anion binding	1
vitamin B6 binding	1
identical protein binding	1
protein dimerization activity	1
amino acid transaminase activity	1
L-methionine:oxo-acid transaminase activity	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AADAT	KYAT1	Q16773	995
AADAT	KMO	O15229	826
AADAT	KYNU	Q16719	796
AADAT	HAAO	P46952	756
AADAT	TDO2	P48775	697
AADAT	QPRT	Q15274	691
AADAT	GPR35	Q9HC97	662
AADAT	TRABD2B	A6NFA1	660
AADAT	GOT2	P00505	639
AADAT	IDO1	P14902	627
AADAT	ASS1	P00966	624
AADAT	ACMSD	Q8TDX5	594
AADAT	IDO2	Q6ZQW0	576
AADAT	AFMID	Q63HM1	543
AADAT	KYAT3	Q6YP21	541

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SPACA3	HSPA5	psi-mi:“MI:0914”(association)	0.530

BioGRID (23): AADAT (Affinity Capture-MS), AADAT (Affinity Capture-RNA), MCFD2 (Co-fractionation), TXNRD2 (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (Co-fractionation), AADAT (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: A7XRY8, D4AU29, D5AKX9, E9F8L8, F8P1W6, O14192, O87320, Q39M27, Q54K00, Q5E9N4, Q64602, Q8N5Z0, Q9WVM8, A4FWW1, B7STY2, O94570, P53090, P61003, Q01856, Q86AG8, Q9Y7S6, P39389, P95957, Q72LL6, H3ZPL1, P10356, P96681, Q2FKF1, Q2G1P1, Q2YUS3, Q5HJR1, Q796Q6, Q7A875, Q99XA5, A0LEA5, A1VDD3, A2BYM6, A2C4T7, A2CC97, A3DK17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	2
Uncertain significance	23
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
146581	GRCh38/hg38 4q31.21-35.2(chr4:145042668-189975519)x3	Pathogenic
148458	GRCh38/hg38 4q32.3-35.2(chr4:166317587-190095391)x1	Pathogenic
151692	GRCh38/hg38 4q33-35.2(chr4:169873508-190018185)x1	Pathogenic
151716	GRCh38/hg38 4q32.3-35.2(chr4:165281036-190018185)x1	Pathogenic
152441	GRCh38/hg38 4q32.1-35.2(chr4:160757699-190091407)x3	Pathogenic
153168	GRCh38/hg38 4q32.3-34.3(chr4:166630207-179820960)	Pathogenic
153493	GRCh38/hg38 4q32.1-33(chr4:155162982-170959553)x1	Pathogenic
154300	GRCh38/hg38 4q32.3-35.2(chr4:168970400-186936738)x1	Pathogenic
155264	GRCh38/hg38 4q32.3-35.2(chr4:168119317-190095391)x3	Pathogenic
1711100	GRCh37/hg19 4q32.1-35.2(chr4:159174483-190957473)x1	Pathogenic
1711166	GRCh37/hg19 4q32.3-35.2(chr4:167779888-190957473)x1	Pathogenic
253590	GRCh37/hg19 4q28.3-35.1(chr4:136912336-184253252)x3	Pathogenic
253606	GRCh37/hg19 4q26-35.2(chr4:119437495-190904301)x3	Pathogenic
253675	GRCh37/hg19 4q32.2-34.2(chr4:162344510-177103037)x1	Pathogenic
2684399	GRCh37/hg19 4q32.3-35.2(chr4:167409608-190957473)x3	Pathogenic
3024631	GRCh37/hg19 4p12-q35.2(chr4:45455621-191003541)x3	Pathogenic
3024634	GRCh37/hg19 4q32.3-35.2(chr4:169060637-191154276)x1	Pathogenic
3062767	GRCh37/hg19 4q24-35.2(chr4:101203509-190957473)x3	Pathogenic
441562	GRCh37/hg19 4q31.3-35.2(chr4:153890440-190957473)x3	Pathogenic
441736	GRCh37/hg19 4q32.2-34.3(chr4:162205710-182329883)x1	Pathogenic
443385	GRCh37/hg19 4q32.3-35.2(chr4:166436844-190957473)x3	Pathogenic
443800	GRCh37/hg19 4q32.1-35.2(chr4:156465633-190957473)x3	Pathogenic
4682610	GRCh37/hg19 4q32.1-35.2(chr4:161355371-190957473)x3	Pathogenic
562986	GRCh37/hg19 4q32.1-35.1(chr4:157552397-183831253)x3	Pathogenic
562995	GRCh37/hg19 4q32.3-35.2(chr4:169969014-190957473)x1	Pathogenic
59484	GRCh38/hg38 4q32.2-34.1(chr4:162723818-172501433)x1	Pathogenic
685014	GRCh37/hg19 4q32.3-35.2(chr4:166623890-190957473)x1	Pathogenic
686652	GRCh37/hg19 4q32.3-35.2(chr4:169607746-190957473)x3	Pathogenic
688407	GRCh37/hg19 4q31.3-35.2(chr4:151174061-190957473)x3	Pathogenic
688995	GRCh37/hg19 4q28.1-35.1(chr4:124873497-185278662)x3	Pathogenic

SpliceAI

2421 predictions. Top by Δscore:

Variant	Effect	Δscore
4:170064682:T:A	donor_gain	1.0000
4:170064728:AACGG:A	donor_gain	1.0000
4:170066409:CTCA:C	donor_loss	1.0000
4:170066410:TCACC:T	donor_loss	1.0000
4:170066411:CA:C	donor_loss	1.0000
4:170066412:A:AC	donor_gain	1.0000
4:170066412:A:AG	donor_loss	1.0000
4:170066413:C:CC	donor_gain	1.0000
4:170066474:TAACC:T	acceptor_gain	1.0000
4:170066477:CC:C	acceptor_gain	1.0000
4:170066478:CC:C	acceptor_gain	1.0000
4:170066479:C:CC	acceptor_gain	1.0000
4:170067385:TGAG:T	acceptor_gain	1.0000
4:170067387:AGC:A	acceptor_loss	1.0000
4:170067388:GCTA:G	acceptor_loss	1.0000
4:170067389:C:CC	acceptor_gain	1.0000
4:170067390:T:G	acceptor_loss	1.0000
4:170069430:CTTTT:C	acceptor_gain	1.0000
4:170069435:C:CC	acceptor_gain	1.0000
4:170069440:A:T	acceptor_gain	1.0000
4:170070653:C:CC	acceptor_gain	1.0000
4:170073131:AATAC:A	donor_loss	1.0000
4:170073132:ATAC:A	donor_loss	1.0000
4:170073133:TA:T	donor_loss	1.0000
4:170073134:A:AT	donor_loss	1.0000
4:170073146:T:TA	donor_gain	1.0000
4:170073342:GCAG:G	acceptor_gain	1.0000
4:170073343:CAG:C	acceptor_gain	1.0000
4:170073343:CAGC:C	acceptor_gain	1.0000
4:170073344:AGC:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015012 (4:170068394 T>C,G), RS1000052607 (4:170066623 T>C), RS1000202628 (4:170095863 C>T), RS1000330744 (4:170086108 A>G), RS1000416079 (4:170092761 T>A,C), RS1000700408 (4:170076878 A>C,G), RS1000763356 (4:170082812 A>G), RS1000943211 (4:170088945 C>T), RS1001116621 (4:170090529 G>A,C), RS1001154776 (4:170071694 G>A), RS1001174476 (4:170075039 T>C), RS1001199453 (4:170078457 T>G), RS1001232930 (4:170081507 A>G), RS1001265438 (4:170091171 C>T), RS1001334387 (4:170079792 T>C)

Disease associations

OMIM: gene MIM:611754 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001856_18	Thyroid hormone levels	4.000000e-07
GCST001856_46	Thyroid hormone levels	5.000000e-09
GCST008164_2	Free thyroxine concentration	4.000000e-10
GCST008757_31	Alcohol consumption	1.000000e-09
GCST009391_607	Metabolite levels	8.000000e-06
GCST010988_86	Adult body size	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0010505	isocitrate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2046259 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

220 measured of 220 human assays (220 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(R)-N-benzyl-1-{5-[difluoro(phenyl)methyl]-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-2-carboxamide	IC50	4 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-methyl-7-oxo-5-(tetrahydro-2H-pyran-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	4.3 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-methyl-7-oxo-5-(piperidin-1-yl)-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	4.4 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-[5-(3-methyl-[1,2,4]oxadiazol-5-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylic acid phenyl ester	IC50	4.7 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-(2,2-difluoroethyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	4.8 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-(5-methyl-9-oxo-5,9-dihydroimidazo[1,2-a][1,3]thiazolo[5,4-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide	IC50	4.9 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-{5-[difluoro(pyridin-2-yl)methyl]-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-2-carboxamide	IC50	5.6 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(N’,N’-dimethylamino)-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	5.6 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(2-fluorophenyl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	6 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-[5-(1-cyanocyclopropyl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylic acid 3-methylphenyl ester	IC50	6.1 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-(7-oxo-5-trifluoromethyl-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide	IC50	6.9 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(2,6-difluorophenyl)-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	7 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-1-[5-(2,4-difluorophenyl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]N-((R)-1-phenylethyl)pyrrolidine-2-carboxamide	IC50	7.1 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	7.3 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(2-hydroxypropan-2-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	7.6 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-methyl-5-(morpholin-4-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	7.9 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-{2-[N’-methyl-N’-(2,2,2-trifluoroethyl)amino]ethyl}-7-oxo-5-trifluoromethyl-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide hydrochloride	IC50	8 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-(5,5-difluoro-10-oxo-5,7,8,10-tetrahydro-6H-pyrido[1,2-a][1,3]thiazolo[5,4-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide	IC50	8.2 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-{5-[1-(fluoromethyl)cyclopropyl]-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-1-carboxylic acid phenyl ester	IC50	8.6 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(2-fluorophenyl)-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	8.7 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(1-fluorocyclopropyl)-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	8.8 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(5S)-5-amino-7-hydroxy-2-[(3-methoxyphenyl)methyl]-4,5-dihydropyrazolo[3,4-b]pyridin-6-one	IC50	8.93 nM	US-8933095: KAT II inhibitors
(R)-N-benzyl-1-[5-(2,6-difluorophenyl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	9 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(2-fluoropropan-2-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	9.7 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-methoxymethyl-7-oxo-6-(tetrahydro-2H-pyran-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	10 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
5-ethyl-6-methyl-2-[(R)-2-(2-phenylaminoacetyl)pyrrolidin-1-yl][1,3]thiazolo[5,4-d]pyrimidin-7(6H)-one	IC50	10 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-(6-methyl-7-oxo-5-phenyl-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide	IC50	11 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[7-oxo-6-(tetrahydro-2H-pyran-4-yl)-5-trifluoromethyl-6,7-dihydro-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	11 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-{5-difluoromethyl-7-oxo-6-[(tetrahydro-2H-pyran-4-yl)methyl]-6,7-dihydro-[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-2-carboxamide	IC50	11 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-{6-methyl-7-oxo-5-[(propan-2-yl)amino]-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-2-carboxamide	IC50	11 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(5S)-5-amino-3-benzyl-7-hydroxy-2-methyl-4,5-dihydropyrazolo[3,4-b]pyridin-6-one	IC50	11.5 nM	US-8933095: KAT II inhibitors
(R)-N-benzyl-1-[5-(3-methyl-[1,2,4]oxadiazol-5-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	12 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
2-[(R)-1-(phenylacetyl)pyrrolidin-2-yl]-5-[1-(trifluoromethyl)cyclopropyl]-6H-[1,3]thiazolo[5,4-d]pyrimidin-7-one	IC50	13 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-[5-(2,4-difluorophenyl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylic acid phenyl ester	IC50	14 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-[5-(3-methyloxetan-3-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylic acid phenyl ester	IC50	14 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[6-methyl-7-oxo-5-(2,4,6-trifluorophenyl)-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	14 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-{5-[(R)-1-(N’,N’-dimethylamino)ethyl]-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-2-carboxamide	IC50	14 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-[7-oxo-5-(propan-2-yl)-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylic acid phenyl ester	IC50	15 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-1-(5-acetyl-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-N-benzylpyrrolidine-2-carboxamide	IC50	15 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-2-{N’-[5-(propan-2-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-N’-methylamino}propionamide	IC50	15 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[7-chloro-6-(2-fluorophenyl)-4-oxo-4,5-dihydro[1,3]thiazolo[4,5-c]pyridin-2-yl]pyrrolidine-2-carboxamide	IC50	15 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[7-chloro-6-(2-fluoropropan-2-yl)-4-oxo-4,5-dihydro[1,3]thiazolo[4,5-c]pyridin-2-yl]pyrrolidine-2-carboxamide	IC50	15 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-(4-fluorobenzyl)-1-[6-methyl-5-(3-methyl-[1,2,4]oxadiazol-5-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	16 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-(6-cyclopentyl-7-oxo-6,7-dihydro-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide	IC50	16 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-(7-cyclopropyl-5-ethyl-4-oxo-4,5-dihydro[1,3]thiazolo[4,5-d]pyridazin-2-yl)pyrrolidine-2-carboxamide	IC50	16 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-{5-[(1,3-dihydro-2H-isoindol-2-yl)methyl]-6-methyl-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-2-carboxamide	IC50	17 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-1-[5-(3-fluoro-5-methylthiophen-2-yl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide	IC50	17 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-N-benzyl-2-{N’-[5-(2-fluorophenyl)-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-N’-methylamino}propionamide	IC50	17 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-[6-methyl-7-oxo-5-(tetrahydro-2H-pyran-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylic acid 3-methylphenyl ester	IC50	18 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound
(R)-2-{5-[1-(methoxymethyl)cyclopropyl]-7-oxo-6,7-dihydro[1,3]thiazolo[5,4-d]pyrimidin-2-yl}pyrrolidine-1-carboxylic acid phenyl ester	IC50	19 nM	US-10065972: Bicyclic or tricyclic heterocyclic compound

ChEMBL bioactivities

405 potent at pChembl≥5 of 418 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.80	Ki	1.6	nM	CHEMBL2347110
8.78	Ki	1.66	nM	CHEMBL2321943
8.72	Ki	1.9	nM	CHEMBL2347108
8.40	IC50	4	nM	CHEMBL5837150
8.37	IC50	4.3	nM	CHEMBL5803808
8.36	IC50	4.4	nM	CHEMBL6000301
8.33	IC50	4.7	nM	CHEMBL5972208
8.32	IC50	4.8	nM	CHEMBL5995858
8.31	IC50	4.9	nM	CHEMBL5992336
8.29	Ki	5.1	nM	CHEMBL3220810
8.27	IC50	5.4	nM	CHEMBL5893418
8.25	IC50	5.6	nM	CHEMBL5847381
8.25	IC50	5.6	nM	CHEMBL5911861
8.22	IC50	6	nM	CHEMBL5870985
8.21	IC50	6.1	nM	CHEMBL6018146
8.16	IC50	6.9	nM	CHEMBL5830731
8.15	Ki	7.1	nM	CHEMBL2321944
8.15	IC50	7	nM	CHEMBL5765391
8.15	IC50	7.1	nM	CHEMBL5834383
8.14	IC50	7.3	nM	CHEMBL5847771
8.12	IC50	7.6	nM	CHEMBL5841345
8.11	Ki	7.7	nM	CHEMBL2049092
8.10	IC50	7.9	nM	CHEMBL5749610
8.10	IC50	8	nM	CHEMBL5794257
8.09	IC50	8.2	nM	CHEMBL5877034
8.07	IC50	8.6	nM	CHEMBL5883304
8.06	IC50	8.8	nM	CHEMBL5947856
8.06	IC50	8.7	nM	CHEMBL6036435
8.05	IC50	8.93	nM	CHEMBL3660154
8.05	IC50	9	nM	CHEMBL5857404
8.01	IC50	9.7	nM	CHEMBL5948782
8.00	IC50	10	nM	CHEMBL5829522
8.00	IC50	10	nM	CHEMBL5774641
7.96	IC50	11	nM	CHEMBL5816205
7.96	IC50	11	nM	CHEMBL5852024
7.96	IC50	11	nM	CHEMBL5898768
7.96	IC50	11	nM	CHEMBL5893418
7.94	IC50	11.5	nM	CHEMBL3660149
7.92	Ki	12	nM	CHEMBL2347115
7.92	IC50	12	nM	CHEMBL5893418
7.92	IC50	12	nM	CHEMBL5938021
7.92	IC50	12	nM	CHEMBL5824661
7.92	IC50	12	nM	CHEMBL5783518
7.89	IC50	13	nM	CHEMBL5850131
7.89	IC50	13	nM	CHEMBL5984732
7.85	Ki	14.2	nM	CHEMBL2047851
7.85	Ki	14	nM	CHEMBL2047851
7.85	IC50	14	nM	CHEMBL6042491
7.85	IC50	14	nM	CHEMBL6055302
7.85	IC50	14	nM	CHEMBL5820200

PubChem BioAssay actives

62 with measured affinity, of 133 total; 38 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
(3S)-3-amino-6-benzyl-1-hydroxy-7-methoxy-3,4-dihydroquinolin-2-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0016	uM
(3S)-3-amino-1-hydroxy-7-methoxy-6-phenoxy-3,4-dihydroquinolin-2-one	727190: Irreversible inhibition of human KAT2 using L-kynurenine as substrate measured every 5 mins over 16 hrs by SpectraMax plate reader analysis	ki	0.0017	uM
(5S)-5-amino-7-hydroxy-2-phenyl-4,5-dihydropyrazolo[3,4-b]pyridin-6-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0019	uM
(3S)-3-amino-1-hydroxy-6-phenoxy-3,4-dihydroquinolin-2-one	727190: Irreversible inhibition of human KAT2 using L-kynurenine as substrate measured every 5 mins over 16 hrs by SpectraMax plate reader analysis	ki	0.0071	uM
(3S)-3-amino-1-hydroxy-7-methoxy-3,4-dihydroquinolin-2-one	727190: Irreversible inhibition of human KAT2 using L-kynurenine as substrate measured every 5 mins over 16 hrs by SpectraMax plate reader analysis	ki	0.0077	uM
(6S)-6-amino-1-benzyl-4-hydroxy-6,7-dihydropyrazolo[4,5-b]pyridin-5-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0120	uM
(3S)-3-amino-1-hydroxy-3,4-dihydroquinolin-2-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0140	uM
(5S)-5-amino-7-hydroxy-3-[(3-methoxyphenyl)methyl]-1-methyl-4,5-dihydropyrazolo[3,4-b]pyridin-6-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0220	uM
(5S)-5-amino-2-benzyl-7-hydroxy-4,5-dihydropyrazolo[3,4-b]pyridin-6-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0230	uM
(3S)-3-amino-7-chloro-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0290	uM
(3S)-3-amino-1-hydroxy-6-(trifluoromethyl)-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0290	uM
(3S)-3-amino-1-hydroxy-6-methyl-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0300	uM
(5S)-5-amino-3-benzyl-7-hydroxy-1-methyl-4,5-dihydropyrazolo[3,4-b]pyridin-6-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0320	uM
(3S)-3-amino-6-chloro-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0360	uM
(3S)-3-amino-1-hydroxy-7-methyl-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0370	uM
(3S)-3-amino-8-fluoro-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0400	uM
(6S)-6-amino-4-hydroxy-2-phenyl-6,7-dihydropyrazolo[4,3-b]pyridin-5-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0410	uM
(3S)-3-amino-5-fluoro-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.0450	uM
(6S)-6-amino-1-benzyl-4-hydroxy-3-(trifluoromethyl)-6,7-dihydropyrazolo[4,3-b]pyridin-5-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ki	0.0480	uM
(3S)-3-amino-1-hydroxy-8-(trifluoromethyl)-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.1740	uM
(3S)-3-amino-1-hydroxy-5-methoxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.1790	uM
(3R)-3-amino-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.2190	uM
(3S)-3-amino-8-chloro-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.2520	uM
2-(5,6-dichloro-1,3-dioxoisoindol-2-yl)-3-phenylpropanoic acid	1996017: Inhibition of human recombinant KATII	ic50	0.3150	uM
(3S)-3-amino-1-hydroxy-5-methyl-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.3190	uM
(5S)-5-amino-7-hydroxy-1-methyl-4,5-dihydropyrazolo[5,4-b]pyridin-6-one	738357: Inhibition of human KAT2 using L-kynurenine as substrate after 15 to 20 hrs by UV-visible spectra analysis	ic50	0.3290	uM
(3S)-3-amino-5-chloro-1-hydroxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.3490	uM
(3S)-3-amino-1-hydroxy-8-methoxy-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	0.5720	uM
benzyl (2R)-2-[6-methyl-5-(morpholin-4-ylmethyl)-7-oxo-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-1-carboxylate	1996019: Inhibition of His-tagged recombinant human KATII	ic50	0.6100	uM
N-(3-chloro-4-methylphenyl)-2-(3-methylbutyl)-3-oxo-2,8-diazaspiro[5.5]undecane-8-carboxamide	1667436: Reversible inhibition of recombinant human KAT2 assessed as reduction in kynurenic acid formation using L-kynurenine as substrate by fluorescence assay	ic50	0.8100	uM
(2S)-6-(4-aminopiperazin-1-yl)-7-fluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid	499349: Inhibition of human recombinant MBP-KAT2 expressed in HEK293 cells assessed as conversion of L-kynurenine to kynurenic acid after 1 hr	ic50	0.9100	uM
(3S)-3-amino-1-hydroxy-8-methyl-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	1.0500	uM
(2R)-6-(4-aminopiperazin-1-yl)-7-fluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid	499349: Inhibition of human recombinant MBP-KAT2 expressed in HEK293 cells assessed as conversion of L-kynurenine to kynurenic acid after 1 hr	ic50	1.5000	uM
3,5-difluoro-N-[5-[2-(3-fluorophenyl)-3-methylbutyl]-1,3,4-thiadiazol-2-yl]benzenesulfonamide	1667436: Reversible inhibition of recombinant human KAT2 assessed as reduction in kynurenic acid formation using L-kynurenine as substrate by fluorescence assay	ic50	1.5488	uM
N-(3-chloro-4-fluorophenyl)-2-(cyclopropylmethyl)-3-oxo-2,8-diazaspiro[5.5]undecane-8-carboxamide	1667436: Reversible inhibition of recombinant human KAT2 assessed as reduction in kynurenic acid formation using L-kynurenine as substrate by fluorescence assay	ic50	2.3988	uM
(3S,4S)-3-amino-1-hydroxy-4-methyl-3,4-dihydroquinolin-2-one	669475: Inhibition of human recombinant KAT2 assessed as conversion of L-kynurenine into kynurenic acid after 15 to 20 hrs	ic50	3.2800	uM
N-(3-ethylphenyl)-2-(3-methylbutyl)-3-oxo-2,8-diazaspiro[5.5]undecane-8-carboxamide	1667436: Reversible inhibition of recombinant human KAT2 assessed as reduction in kynurenic acid formation using L-kynurenine as substrate by fluorescence assay	ic50	4.3652	uM
2-cyclopropyl-N-(3,5-dimethylphenyl)-3-oxo-2,8-diazaspiro[5.5]undecane-8-carboxamide	1667436: Reversible inhibition of recombinant human KAT2 assessed as reduction in kynurenic acid formation using L-kynurenine as substrate by fluorescence assay	ic50	4.5000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
uranyl acetate	affects expression	1
sodium arsenite	decreases expression	1
K 7174	decreases expression	1
enzalutamide	decreases expression	1
NSC 689534	decreases expression, affects binding	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Uranium	affects expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases expression	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

25 unique, capped per target: 25 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1219087	Binding	Inhibition of human recombinant MBP-KAT2 expressed in HEK293 cells assessed as conversion of L-kynurenine to kynurenic acid after 1 hr	Crystal structure-based selective targeting of the pyridoxal 5’-phosphate dependent enzyme kynurenine aminotransferase II for cognitive enhancement. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2R2	Abcam HEK293T AADAT KO	Transformed cell line	Female

Clinical trials (associated diseases)

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