TXK

Summary

TXK (TXK tyrosine kinase, HGNC:12434) is a protein-coding gene on chromosome 4p12, encoding Tyrosine-protein kinase TXK (P42681). Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response.

Predicted to enable non-membrane spanning protein tyrosine kinase activity. Involved in positive regulation of macromolecule biosynthetic process; positive regulation of type II interferon-mediated signaling pathway; and protein autophosphorylation. Located in cytosol; nuclear lumen; and plasma membrane.

Source: NCBI Gene 7294 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 74 total
• Druggable target: yes — 31 molecules with ChEMBL bioactivity
• Transcription factor: yes — 136 downstream targets (CollecTRI)
• MANE Select transcript: NM_003328

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12434
Approved symbol	TXK
Name	TXK tyrosine kinase
Location	4p12
Locus type	gene with protein product
Status	Approved
Aliases	TKL, PSCTK5, BTKL, RLK
Ensembl gene	ENSG00000074966
Ensembl biotype	protein_coding
OMIM	600058
Entrez	7294

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264316, ENST00000506073, ENST00000507351, ENST00000509681, ENST00000510457, ENST00000514937, ENST00000960124

RefSeq mRNA: 1 — MANE Select: NM_003328 NM_003328

CCDS: CCDS3480

Canonical transcript exons

ENST00000264316 — 15 exons

Exon	Start	End
ENSE00001073099	48089750	48089824
ENSE00001073100	48066393	48067705
ENSE00001073101	48073935	48074053
ENSE00001073102	48076402	48076466
ENSE00001073103	48079912	48080128
ENSE00001073104	48086466	48086637
ENSE00001073105	48134155	48134250
ENSE00003538867	48094077	48094204
ENSE00003560253	48113207	48113309
ENSE00003571754	48071517	48071674
ENSE00003576182	48095143	48095222
ENSE00003577462	48110538	48110603
ENSE00003629866	48114348	48114402
ENSE00003657702	48112307	48112512
ENSE00003659892	48104901	48104955

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 90.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.9766 / max 426.0797, expressed in 151 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52067	3.5394	126
52066	0.2766	49
52063	0.0508	21
52064	0.0297	15
52061	0.0283	4
52059	0.0200	6
52065	0.0190	7
52060	0.0128	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	90.65	gold quality
blood	UBERON:0000178	83.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.84	gold quality
spleen	UBERON:0002106	80.30	gold quality
lymph node	UBERON:0000029	80.05	gold quality
vermiform appendix	UBERON:0001154	75.42	gold quality
lower esophagus mucosa	UBERON:0035834	74.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.15	gold quality
right uterine tube	UBERON:0001302	73.38	gold quality
leukocyte	CL:0000738	71.61	gold quality
bone marrow cell	CL:0002092	71.61	gold quality
right lobe of liver	UBERON:0001114	71.10	gold quality
upper lobe of left lung	UBERON:0008952	71.04	gold quality
tonsil	UBERON:0002372	70.46	gold quality
small intestine	UBERON:0002108	70.17	gold quality
gall bladder	UBERON:0002110	69.89	gold quality
mononuclear cell	CL:0000842	69.86	gold quality
caecum	UBERON:0001153	69.66	gold quality
monocyte	CL:0000576	69.44	gold quality
placenta	UBERON:0001987	69.23	gold quality
right lung	UBERON:0002167	69.12	gold quality
upper lobe of lung	UBERON:0008948	68.71	gold quality
esophagus mucosa	UBERON:0002469	67.04	gold quality
rectum	UBERON:0001052	66.55	gold quality
bone marrow	UBERON:0002371	66.45	gold quality
right adrenal gland cortex	UBERON:0035827	66.39	gold quality
right adrenal gland	UBERON:0001233	65.89	gold quality
mucosa of transverse colon	UBERON:0004991	65.87	gold quality
metanephros cortex	UBERON:0010533	65.57	gold quality
skin of leg	UBERON:0001511	64.90	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	501.19
E-CURD-122	yes	42.77
E-MTAB-6678	yes	27.65
E-CURD-46	yes	23.67
E-ANND-3	yes	21.86
E-HCAD-9	yes	21.00
E-CURD-88	yes	20.79
E-MTAB-8410	yes	10.82
E-MTAB-9067	yes	5.27
E-CURD-112	yes	4.44
E-GEOD-75367	no	500.90

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

136 targets.

Target	Regulation
ABCA3
ABL1
ACTA2
ADAM2
AKR1B1
AKT1
ALK
ANGPT1
ANGPT2
ATP11C
BCR
BDNF
BDNF-AS
BECN1
BRCA1
BTK
CD2
CDH1
CDKN1A
CDKN1B
CDKN1C
CEACAM1
CEL
CFI
CFTR
CIITA
COL1A2
CSF1
CTSK
CTTN

Upstream regulators (CollecTRI, top): IRF6, TXK, ZHX2

miRNA regulators (miRDB)

81 targeting TXK, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4420	99.82	70.08	1624

Literature-anchored findings (GeneRIF, showing 5)

• fuctions as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription (PMID:11859127)
• Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with Behcet’s disease. (PMID:16809408)
• Itk and Txk exert their effects on T helper (Th) cell differentiation and function at the level of expression; transgenic Txk is not a specific regulator of Th1 responses. (PMID:18941202)
• These data indicate that PRN694 is a highly selective and potent covalent inhibitor of ITK and RLK, and its extended target residence time enables durable attenuation of effector cells in vitro and in vivo. (PMID:25593320)
• Characterization, evolution, and abiotic stress responses of leucine-rich repeat receptor-like protein kinases (LRR-RLK) in Liriodendron chinense. (PMID:39085785)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Txk	ENSMUSG00000054892
rattus_norvegicus	Txk	ENSRNOG00000025925

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase TXK — P42681 (reviewed: P42681)

Alternative names: Protein-tyrosine kinase 4, Resting lymphocyte kinase

All UniProt accessions (5): P42681, D6R9F2, D6RA14, D6RBM7, E7EQN8

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation leads to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Also contributes to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with PARP1 and EEF1A1. Within the complex, phosphorylates both PARP1 and EEF1A1. Also phosphorylates key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates ‘Tyr-201’ of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.

Subunit / interactions. Interacts with PARP1 and EEF1A1. Interacts with SH2D2A. Interacts with FYN.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Expressed in T-cells and some myeloid cell lines. Expressed in Th1/Th0 cells with IFN-gamma-producing potential.

Post-translational modifications. Phosphorylated at Tyr-420 by FYN. Autophosphorylation at Tyr-91 is critical for the activation of TXK, leading to the up-regulation of IFN-gamma gene transcription. The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location.

Activity regulation. Activated by phosphorylation by FYN.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.

RefSeq proteins (1): NP_003319* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035579	TXK_SH3	Domain
IPR035870	Txk_SH2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (26 total): strand 7, domain 3, sequence variant 3, modified residue 2, mutagenesis site 2, helix 2, binding site 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DM0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42681-F1	79.88	0.47

Functional residue map

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

Catalytic / active sites (1): 390 (proton acceptor)

Ligand- & substrate-binding residues (2): 277–285; 299

Post-translational modifications (2): 91, 420

Mutagenesis-validated functional residues (2):

Position	Phenotype
91	reduces expression levels if ifn-gamma.
299	impairs kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2871809	FCERI mediated Ca+2 mobilization

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): positive regulation of cytokine production (GO:0001819), adaptive immune response (GO:0002250), protein phosphorylation (GO:0006468), regulation of gene expression (GO:0010468), positive regulation of type II interferon production (GO:0032729), positive regulation of transcription by RNA polymerase II (GO:0045944), protein autophosphorylation (GO:0046777), T cell receptor signaling pathway (GO:0050852), positive regulation of type II interferon-mediated signaling pathway (GO:0060335), immune system process (GO:0002376)

GO Molecular Function (8): non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fc epsilon receptor (FCERI) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nuclear lumen	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
immune response	1
phosphorylation	1
protein modification process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
protein phosphorylation	1
antigen receptor-mediated signaling pathway	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of response to type II interferon	1
type II interferon-mediated signaling pathway	1
regulation of type II interferon-mediated signaling pathway	1
biological_process	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXK	TBX21	Q9UL17	747
TXK	EEF1A1	P04719	651
TXK	CALM1	P02593	639
TXK	PLEK2	Q9NYT0	626
TXK	PLEK	P08567	619
TXK	SH2D2A	Q9NP31	602
TXK	GATA3	P23771	601
TXK	STAP1	Q9ULZ2	580
TXK	VAV1	P15498	573
TXK	NCK1	P16333	555
TXK	PLCG1	P19174	538
TXK	GRB2	P29354	534
TXK	STAM2	O75886	517
TXK	CD4	P01730	510
TXK	LCP2	Q13094	506
TXK	IL2RB	P14784	506

IntAct

82 interactions, top by confidence:

A	B	Type	Score
TXK	DUSP6	psi-mi:“MI:0915”(physical association)	0.560
TXK	SOCS3	psi-mi:“MI:0915”(physical association)	0.560
TXK	TNS4	psi-mi:“MI:0915”(physical association)	0.560
TXK	STAP2	psi-mi:“MI:0915”(physical association)	0.560
TXK	ZNF587	psi-mi:“MI:0915”(physical association)	0.560
TXK	IKZF4	psi-mi:“MI:0915”(physical association)	0.560
TXK	IKZF1	psi-mi:“MI:0915”(physical association)	0.560
TXK	EFHC2	psi-mi:“MI:0915”(physical association)	0.560
TXK	RBAK	psi-mi:“MI:0915”(physical association)	0.560
TXK	CRK	psi-mi:“MI:0915”(physical association)	0.560
NCK2	TXK	psi-mi:“MI:0915”(physical association)	0.560
	TXK	psi-mi:“MI:0915”(physical association)	0.560
TXK	CBY2	psi-mi:“MI:0915”(physical association)	0.560
PIK3R1	TXK	psi-mi:“MI:0915”(physical association)	0.560
TXK	PRDM14	psi-mi:“MI:0915”(physical association)	0.560
SOCS6	TXK	psi-mi:“MI:0915”(physical association)	0.560
JRK	TXK	psi-mi:“MI:0915”(physical association)	0.560
TXK	GRB10	psi-mi:“MI:0915”(physical association)	0.560
TXK	GRB2	psi-mi:“MI:0915”(physical association)	0.560
TXK	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
TXK	ZNF792	psi-mi:“MI:0915”(physical association)	0.560
SOCS3	TXK	psi-mi:“MI:0915”(physical association)	0.560
DOK2	TXK	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (52): TXK (Two-hybrid), TXK (Two-hybrid), GRB10 (Two-hybrid), IKZF4 (Two-hybrid), ZNF835 (Two-hybrid), TNS4 (Two-hybrid), DUSP6 (Two-hybrid), CCDC33 (Two-hybrid), PIK3R1 (Two-hybrid), RBAK (Two-hybrid), DOK2 (Two-hybrid), PRDM14 (Two-hybrid), CRK (Two-hybrid), SOCS6 (Two-hybrid), SPERT (Two-hybrid)

ESM2 similar proteins: A8WZ92, F1N9Y5, G5ECJ6, O01798, O13147, O19064, O60674, P00521, P00528, P08487, P10686, P16885, P19174, P24135, P24604, P26818, P29350, P29351, P34892, P35626, P35991, P42680, P42681, P42687, P43403, P43404, P43405, P48025, P51813, P53356, P81718, P97504, Q00655, Q05688, Q06124, Q06187, Q07407, Q09639, Q22070, Q24145

Diamond homologs: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, G5EE56, O45539, P00519, P00520, P00521, P00522, P00523, P00524, P00525, P00526, P00527, P00528, P00544, P03949, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08630, P08631, P09324, P09769, P10447, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P15054

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
TXK	“up-regulates activity”	LCP2	phosphorylation
SRC	“up-regulates activity”	TXK	phosphorylation
TXK	up-regulates	LCP2	phosphorylation
TXK	“up-regulates quantity by stabilization”	CTLA4	phosphorylation
TXK	up-regulates	TXK	phosphorylation
FYN	“up-regulates activity”	TXK	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Signaling by SCF-KIT	5	65.3×	1e-06
Constitutive Signaling by Aberrant PI3K in Cancer	6	40.1×	1e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	30.6×	2e-06
PIP3 activates AKT signaling	6	21.1×	7e-06
RAF/MAP kinase cascade	6	19.3×	1e-05
Signaling by Receptor Tyrosine Kinases	5	13.6×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor protein tyrosine kinase signaling pathway	5	36.2×	7e-05
intracellular signal transduction	5	7.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2886 predictions. Top by Δscore:

Variant	Effect	Δscore
4:48071511:GCTTA:G	donor_loss	1.0000
4:48071512:CTTA:C	donor_loss	1.0000
4:48071513:TTAC:T	donor_loss	1.0000
4:48071514:TACC:T	donor_loss	1.0000
4:48071515:A:C	donor_loss	1.0000
4:48071516:CCT:C	donor_gain	1.0000
4:48071670:AACTC:A	acceptor_gain	1.0000
4:48071672:CTC:C	acceptor_gain	1.0000
4:48071673:TC:T	acceptor_gain	1.0000
4:48071674:CC:C	acceptor_gain	1.0000
4:48071675:C:A	acceptor_loss	1.0000
4:48071675:C:CC	acceptor_gain	1.0000
4:48071682:C:CT	acceptor_gain	1.0000
4:48071683:A:T	acceptor_gain	1.0000
4:48071687:A:C	acceptor_gain	1.0000
4:48079906:ACTT:A	donor_loss	1.0000
4:48079908:TTA:T	donor_loss	1.0000
4:48079909:TA:T	donor_loss	1.0000
4:48079910:A:AC	donor_gain	1.0000
4:48079911:C:CC	donor_gain	1.0000
4:48110536:A:AC	donor_gain	1.0000
4:48110537:C:CC	donor_gain	1.0000
4:48112508:TTGGA:T	acceptor_gain	1.0000
4:48112513:C:CC	acceptor_gain	1.0000
4:48112515:G:C	acceptor_gain	1.0000
4:48113305:TTTGT:T	acceptor_gain	1.0000
4:48113306:TTGT:T	acceptor_gain	1.0000
4:48113307:TGT:T	acceptor_gain	1.0000
4:48113310:C:CC	acceptor_gain	1.0000
4:48113315:A:C	acceptor_gain	1.0000

AlphaMissense

3468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:48073998:A:G	W432R	0.998
4:48073998:A:T	W432R	0.998
4:48076417:T:A	D408V	0.998
4:48086525:C:A	K299N	0.998
4:48086525:C:G	K299N	0.998
4:48095200:A:T	V175D	0.998
4:48067693:G:T	R510S	0.997
4:48073944:A:G	W450R	0.997
4:48073944:A:T	W450R	0.997
4:48076416:G:C	D408E	0.997
4:48076416:G:T	D408E	0.997
4:48079916:T:G	D390A	0.997
4:48076417:T:G	D408A	0.996
4:48076452:A:C	C396W	0.996
4:48086479:C:G	A315P	0.996
4:48086576:A:C	F282L	0.996
4:48086576:A:T	F282L	0.996
4:48086578:A:G	F282L	0.996
4:48095205:A:C	F173L	0.996
4:48095205:A:T	F173L	0.996
4:48095207:A:G	F173L	0.996
4:48104954:A:G	W150R	0.996
4:48104954:A:T	W150R	0.996
4:48071525:A:G	W503R	0.995
4:48071525:A:T	W503R	0.995
4:48071663:A:G	W457R	0.995
4:48071663:A:T	W457R	0.995
4:48079916:T:A	D390V	0.995
4:48079919:C:G	R389T	0.995
4:48076454:A:G	C396R	0.994

dbSNP variants (sampled 300 via entrez): RS1000054208 (4:48104252 T>A), RS1000129777 (4:48102323 T>C,G), RS1000177479 (4:48103073 G>A,C), RS1000280972 (4:48124855 A>G), RS10003132 (4:48118236 A>G), RS1000396373 (4:48095903 G>A), RS1000443689 (4:48089037 A>G), RS1000566373 (4:48122525 T>C), RS1000614204 (4:48129103 G>A), RS1000643817 (4:48116121 T>A), RS1000662836 (4:48068718 G>C), RS1000664056 (4:48096123 T>C), RS1000696152 (4:48115816 C>T), RS10007288 (4:48088118 C>A,G,T), RS1000729944 (4:48097638 A>G)

Disease associations

OMIM: gene MIM:600058 | 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
GCST001729_12	Crohn’s disease	2.000000e-08
GCST004616_1	Platelet distribution width	5.000000e-11
GCST009597_261	Multiple sclerosis	1.000000e-11
GCST90002395_570	Mean platelet volume	7.000000e-17
GCST90002401_144	Platelet distribution width	2.000000e-20
GCST90011899_157	Aspartate aminotransferase levels	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4296642 (PROTEIN FAMILY), CHEMBL4367 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

31 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 390,939 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3707348	ACALABRUTINIB	4	4,504
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL4071161	TIRABRUTINIB	4	2,170
CHEMBL4085457	RITLECITINIB	4	708
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL3702854	RILZABRUTINIB	3	851
CHEMBL4483575	REMIBRUTINIB	3	569
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2
CHEMBL3301625	SPEBRUTINIB	2
CHEMBL3900554	BMS-986142	2
CHEMBL4114766	ATUZABRUTINIB	2
CHEMBL4297674	BRANEBRUTINIB	2
CHEMBL475251	R-406	2
CHEMBL572878	TOZASERTIB	2
CHEMBL5817577	SOQUELITINIB	2
CHEMBL607707	PELITINIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Tec family

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
bosutinib	Inhibition	9.52	pIC50
compound 23 [PMID: 17600705]	Inhibition	9.4	pIC50
modzatinib	Inhibition	9.08	pIC50
compound 38 [PMID: 24915291]	Inhibition	8.85	pIC50
PRN694	Inhibition	8.85	pIC50
compound 31 [PMID: 24915291]	Inhibition	8.72	pIC50
ibrutinib	Inhibition	8.7	pIC50
compound 9 [PMID: 26006010]	Inhibition	7.39	pIC50
compound 7 [PMID: 22464456]	Inhibition	7.11	pIC50
acalabrutinib	Inhibition	6.43	pIC50

Binding affinities (BindingDB)

62 measured of 62 human assays (62 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-1-hydroxypropan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.04 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-1-hydroxy-3,3-dimethylbutan-2-yl)-amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.05 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
(R)-N-(1-((1-acryloylpyrrolidin-2-yl)methyl)-5-(((cyclopropylmethyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.08 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((R)-1-hydroxypropan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.09 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
(R)-N-(1-((1-acryloylpyrrolidin-2-yl)methyl)-5-(((2-hydroxy-2-methylpropyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.09 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((R)-1-hydroxy-3,3-dimethylbutan-2-yl)-amino)-methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.1 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethyl-butan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	0.3 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((R)-1-hydroxy-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)-thiophene-2-carboxamide formate	IC50	0.6 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
1-[3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	IC50	0.8 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-1-hydroxy-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide formate	IC50	0.8 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-1-hydroxypropan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)-thiophene-2-carboxamide formate	IC50	0.8 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((R)-1-methoxypropan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)-thiophene-2-carboxamide formate	IC50	0.8 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((R)-1-hydroxypropan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)-thiophene-2-carboxamide formate	IC50	0.9 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
(R)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(((cyclopropyl-methyl)-amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	1.1 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
(R)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(hydroxymethyl)-1H-benzo[d]imidazol-2-yl)-5-(oxazol-5-yl)thiophene-2-carboxamide	IC50	1.4 nM	US-9932329: Benzimidazole derivatives as RLK and ITK inhibitors
Staurosporine	KD	1.7 nM
N-[3-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-4-propan-2-yloxycyclohexa-2,4-dien-1-yl]-1H-pyrazole-4-carboxamide	IC50	2.2 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
AVL-292	IC50	3.2 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(3-cyclopropylphenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	8 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(3-chlorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	16 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	17 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	21 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-3-(1-benzylpyrazol-4-yl)-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)pyrazole-4-carboxamide	IC50	24 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-fluoro-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	25 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
BMS-354825	KD	27 nM
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2-chlorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	27 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2-fluorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	27 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	29 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	33 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2-chloro-3-fluorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	34 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2-chloro-5-fluorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	35 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2-cyanophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	37 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[3-(difluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	37 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2,3-difluorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	38 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	46 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-cyano-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	50 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[3-fluoro-2-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	54 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(3-fluorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	56 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-fluoro-5-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	64 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(4-fluorophenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	78 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	85 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(1R)-1-[3-(trifluoromethyl)phenyl]ethyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	120 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(3-chlorophenyl)methyl]pyrazol-4-yl]-5-(methylamino)pyrazole-4-carboxamide	IC50	120 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	120 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[6-(trifluoromethyl)-2-pyridinyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	150 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[(2-methylphenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	160 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[3-methyl-1-[(3-methylphenyl)methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	160 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-5-(methylamino)-3-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	280 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors

ChEMBL bioactivities

498 potent at pChembl≥5 of 504 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	IC50	0.12	nM	CHEMBL5802491
9.85	IC50	0.14	nM	CHEMBL4206765
9.85	IC50	0.14	nM	CHEMBL4214683
9.80	IC50	0.16	nM	CHEMBL4217959
9.80	IC50	0.16	nM	CHEMBL5827965
9.74	IC50	0.18	nM	CHEMBL4203077
9.74	IC50	0.18	nM	CHEMBL4219011
9.74	IC50	0.18	nM	CHEMBL5785815
9.70	IC50	0.2	nM	CHEMBL4207292
9.70	IC50	0.2	nM	CHEMBL5945729
9.70	IC50	0.2	nM	CHEMBL5898859
9.70	IC50	0.2	nM	CHEMBL5884165
9.70	IC50	0.2	nM	CHEMBL5978552
9.70	IC50	0.2	nM	CHEMBL5872571
9.68	IC50	0.21	nM	CHEMBL4211372
9.68	IC50	0.21	nM	CHEMBL5916137
9.68	IC50	0.21	nM	CHEMBL5780981
9.66	IC50	0.22	nM	CHEMBL4208358
9.66	IC50	0.22	nM	CHEMBL5770715
9.66	IC50	0.22	nM	CHEMBL5787507
9.62	IC50	0.24	nM	CHEMBL5872554
9.62	IC50	0.24	nM	CHEMBL6054891
9.60	IC50	0.25	nM	CHEMBL4216187
9.59	IC50	0.26	nM	CHEMBL5947197
9.59	IC50	0.26	nM	CHEMBL5949895
9.57	IC50	0.27	nM	CHEMBL5996989
9.55	IC50	0.28	nM	CHEMBL5752655
9.54	IC50	0.29	nM	CHEMBL4204572
9.54	IC50	0.29	nM	CHEMBL5750752
9.54	IC50	0.29	nM	CHEMBL5831208
9.52	IC50	0.3	nM	CHEMBL5878223
9.52	IC50	0.3	nM	CHEMBL5913558
9.52	IC50	0.3	nM	CHEMBL5778702
9.52	IC50	0.3	nM	CHEMBL5751446
9.52	IC50	0.3	nM	CHEMBL5892177
9.52	IC50	0.3	nM	DASATINIB
9.51	IC50	0.31	nM	CHEMBL5964869
9.49	IC50	0.32	nM	CHEMBL4216529
9.49	IC50	0.32	nM	CHEMBL5875694
9.49	IC50	0.32	nM	CHEMBL5960714
9.48	IC50	0.33	nM	CHEMBL5773850
9.47	IC50	0.34	nM	CHEMBL5846327
9.47	IC50	0.34	nM	CHEMBL5920665
9.46	IC50	0.35	nM	CHEMBL5948251
9.43	IC50	0.37	nM	CHEMBL4206487
9.43	IC50	0.37	nM	CHEMBL5782207
9.43	IC50	0.37	nM	CHEMBL5743673
9.43	IC50	0.37	nM	CHEMBL5862546
9.41	IC50	0.39	nM	CHEMBL4202941
9.41	IC50	0.39	nM	CHEMBL5946372

PubChem BioAssay actives

155 with measured affinity, of 796 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
Ritlecitinib	1802326: TR-FRET Competition Assay from Article 10.1021/acschembio.6b00677: “Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition.”	ki	0.0001	uM
5-(2-oxo-1H-pyridin-4-yl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0001	uM
5-(2-methylpyrimidin-4-yl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0001	uM
N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
5-(2-amino-4-pyridinyl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
5-[2-(methylamino)-4-pyridinyl]-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
5-(1,3-oxazol-5-yl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
5-(2-aminopyrimidin-4-yl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
N-[5-fluoro-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	507700: Inhibition of TXK	ic50	0.0003	uM
N-[5-(methylamino)-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0003	uM
N-[5-[[(4-hydroxycyclohexyl)amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0003	uM
5-(1,1-difluoroethyl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0003	uM
5-(difluoromethyl)-N-[5-[[(3-hydroxy-2,2-dimethylpropyl)amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0004	uM
N-[5-[[(3-hydroxy-2,2-dimethylpropyl)amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0004	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzenesulfonamide	308764: Inhibition of Txk	ic50	0.0004	uM
4-cyano-N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]benzamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0005	uM
5-(difluoromethyl)-N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0006	uM
N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-1,2-thiazole-5-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0006	uM
Ibrutinib	1878122: Binding affinity to TXK (unknown origin) assessed as dissociation constant by KINOMEscan analysis	kd	0.0006	uM
5-(difluoromethyl)-N-[5-(morpholin-4-ylmethyl)-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0007	uM
N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]-1,3-thiazole-5-carboxamide	1384814: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0008	uM
(E)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile	1850196: Inhibition of RLK (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0012	uM
(E)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile	1850250: Inhibition of RLK (unknown origin) using peptide substrate in presence of ATP	ic50	0.0012	uM
2-methyl-N-[2-[3-[[2-(prop-2-enoylamino)acetyl]amino]anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1155506: Inhibition of Rlk (unknown origin) after 1 hr by HTRF assay	ic50	0.0014	uM
2-methyl-N-[2-[3-(prop-2-enoylamino)anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1155506: Inhibition of Rlk (unknown origin) after 1 hr by HTRF assay	ic50	0.0019	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	308764: Inhibition of Txk	ic50	0.0020	uM
(7S)-2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-3,3a,4,5,6,7-hexahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1871763: Inhibition of TXK (unknown origin)	ic50	0.0022	uM
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide	1399234: Inhibition of TXK (unknown origin)	ic50	0.0023	uM
N-[(7S)-4-amino-6-methylidene-5-(4-phenoxyphenyl)-7,8-dihydropyrimido[5,4-b]pyrrolizin-7-yl]prop-2-enamide	1375527: Inhibition of recombinant human TXK using Poly(Glu, Tyr) 4:1 as substrate after 1 hr by ELISA	ic50	0.0025	uM
Zanubrutinib	1615374: Inhibition of human TXK using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	ic50	0.0029	uM
(7S)-2-(3,5-dimethoxy-4-methylphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948224: Inhibition of human TXK preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay	ic50	0.0034	uM
(E)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile	1850196: Inhibition of RLK (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0034	uM
4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide	1656254: Inhibition of TXK (unknown origin)	ic50	0.0050	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734760: Inhibition of human recombinant TXK (256 to end residues) using GEEPLYWSFPAKKK as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0060	uM
3-chloro-4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	1678395: Inhibition of TXK (unknown origin)	ic50	0.0100	uM
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399234: Inhibition of TXK (unknown origin)	ic50	0.0150	uM
4-[3-[(6R,8aS)-1,1-dimethyl-3-oxo-6,7,8,8a-tetrahydro-5H-[1,3]oxazolo[3,4-a]pyridin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721760: Inhibition of TXK (unknown origin)	ic50	0.0150	uM
4-[7-methoxy-6-(5-morpholin-4-ylpent-2-ynoylamino)quinolin-4-yl]oxy-N-pyridin-2-ylbenzamide	1720525: Inhibition of recombinant human N-terminal GST-tagged TXK (260 to 527 residues) expressed in baculovirus expression system using tyrosine-6 peptide as substrate preincubated for 1 hr in presence of ATP by Z’-LYTE assay	ic50	0.0190	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715134: Inhibition of human TXK using EAIYAAPFAKKK as substrate by [gamma-33P]-ATP assay	ic50	0.0191	uM
Acalabrutinib	1878122: Binding affinity to TXK (unknown origin) assessed as dissociation constant by KINOMEscan analysis	kd	0.0240	uM
2,3-dimethyl-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-1H-indole-7-carboxamide	1399234: Inhibition of TXK (unknown origin)	ic50	0.0260	uM
3-[[4-[(5-methyl-1H-indazol-4-yl)amino]pyrimidin-2-yl]amino]benzamide	308764: Inhibition of Txk	ic50	0.0280	uM
(7S)-3-fluoro-4-[3-(8-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1319787: Inhibition of TXK (unknown origin)	ic50	0.0280	uM
4-[8-amino-3-[(3R)-1-(3-methyloxetane-3-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711667: Inhibition of human TXK	ic50	0.0320	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711667: Inhibition of human TXK	ic50	0.0330	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721760: Inhibition of TXK (unknown origin)	ic50	0.0330	uM
(7S)-7-(1-but-2-ynoylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948224: Inhibition of human TXK preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay	ic50	0.0340	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624911: Binding constant for TXK kinase domain	kd	0.0350	uM
N-[3-[[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239408: Inhibition of TXK (unknown origin) by Z’-Lyte assay	ic50	0.0360	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	3
(+)-JQ1 compound	decreases expression	2
Nickel	increases expression	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Vehicle Emissions	decreases expression	1
Formaldehyde	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Isotretinoin	increases expression, affects cotreatment	1
Aflatoxin M1	decreases expression	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	decreases expression	1

ChEMBL screening assays

290 unique, capped per target: 286 binding, 3 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1035869	Binding	Binding affinity to human TXK at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem
CHEMBL4023730	ADMET	Inhibition of human full length GST-tagged TXK expressed in baculovirus at 1 uM by Z’-LYTE assay	Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development. — J Med Chem
CHEMBL5209940	Functional	Affinity Phenotypic Cellular interaction (CellTiter-Glo® Luminescent Cell Viability Assay (Promega; growth inhibitory activity in Rec-1 cells)) EUB0000646a TXK	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Clinical trials (associated diseases)

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