TEC

Summary

TEC (tec protein tyrosine kinase, HGNC:11719) is a protein-coding gene on chromosome 4p12-p11, encoding Tyrosine-protein kinase Tec (P42680). Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton.

The protein encoded by this gene belongs to the Tec family of non-receptor protein-tyrosine kinases containing a pleckstrin homology domain. Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein coupled receptors, and integrin molecules. They are also key players in the regulation of the immune functions. Tec kinase is an integral component of T cell signaling and has a distinct role in T cell activation. This gene may be associated with myelodysplastic syndrome.

Source: NCBI Gene 7006 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 73 total — 1 likely-pathogenic
• Druggable target: yes — 39 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_003215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11719
Approved symbol	TEC
Name	tec protein tyrosine kinase
Location	4p12-p11
Locus type	gene with protein product
Status	Approved
Aliases	PSCTK4
Ensembl gene	ENSG00000135605
Ensembl biotype	protein_coding
OMIM	600583
Entrez	7006

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000381501, ENST00000505452, ENST00000511150, ENST00000511471, ENST00000515146, ENST00000955075, ENST00000955076, ENST00000955077, ENST00000955078

RefSeq mRNA: 1 — MANE Select: NM_003215 NM_003215

CCDS: CCDS3481

Canonical transcript exons

ENST00000381501 — 18 exons

Exon	Start	End
ENSE00000714104	48171368	48171449
ENSE00000969532	48176082	48176186
ENSE00000969536	48163702	48163767
ENSE00001488831	48135783	48137499
ENSE00001488859	48228477	48228659
ENSE00001488860	48269752	48269838
ENSE00003460876	48146325	48146399
ENSE00003473541	48156680	48156734
ENSE00003477465	48145408	48145579
ENSE00003537921	48170248	48170376
ENSE00003550511	48168586	48168626
ENSE00003582538	48138904	48139022
ENSE00003588173	48167778	48167953
ENSE00003590863	48138665	48138822
ENSE00003604200	48141355	48141419
ENSE00003605198	48145079	48145295
ENSE00003658054	48149557	48149690
ENSE00003684758	48150863	48150942

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 83.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1554 / max 902.3333, expressed in 916 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52072	4.1554	916

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.81	gold quality
lower esophagus mucosa	UBERON:0035834	83.22	gold quality
bone marrow cell	CL:0002092	82.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.70	gold quality
esophagus mucosa	UBERON:0002469	78.37	gold quality
skin of leg	UBERON:0001511	77.99	gold quality
skin of abdomen	UBERON:0001416	77.79	gold quality
monocyte	CL:0000576	76.84	gold quality
leukocyte	CL:0000738	76.28	gold quality
right uterine tube	UBERON:0001302	74.65	gold quality
zone of skin	UBERON:0000014	74.13	gold quality
rectum	UBERON:0001052	73.88	gold quality
right lung	UBERON:0002167	73.54	gold quality
right adrenal gland cortex	UBERON:0035827	73.54	gold quality
upper lobe of left lung	UBERON:0008952	72.86	gold quality
right lobe of liver	UBERON:0001114	72.54	gold quality
esophagus	UBERON:0001043	72.10	gold quality
left adrenal gland cortex	UBERON:0035825	71.98	gold quality
left adrenal gland	UBERON:0001234	71.78	gold quality
smooth muscle tissue	UBERON:0001135	71.73	gold quality
calcaneal tendon	UBERON:0003701	71.67	gold quality
minor salivary gland	UBERON:0001830	71.57	gold quality
right adrenal gland	UBERON:0001233	71.38	gold quality
upper lobe of lung	UBERON:0008948	70.29	gold quality
adrenal cortex	UBERON:0001235	70.08	gold quality
ectocervix	UBERON:0012249	70.04	gold quality
islet of Langerhans	UBERON:0000006	69.95	gold quality
colonic epithelium	UBERON:0000397	69.71	silver quality
small intestine Peyer’s patch	UBERON:0003454	69.71	gold quality
descending thoracic aorta	UBERON:0002345	69.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, NFKB, NR4A3, NRG1, RELA, SP1, SPI1

miRNA regulators (miRDB)

58 targeting TEC, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4743-3P	99.62	68.12	2095

Literature-anchored findings (GeneRIF, showing 18)

• Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils (PMID:11940595)
• The AF2 domain of the orphan nuclear receptor is essential for the transcriptional activity of the oncogenic fusion protein EWS (PMID:12049818)
• specificity in tyrosine phosphorylation of SH3 domains in vitro is high and, therefore, SH3 domain phosphorylation is required for a distinct function in signaling (PMID:12573241)
• Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase Cgamma (PLC-gamma) phosphorylation and NFAT (nuclear factor of activated T cells) activation. (PMID:14993283)
• Btk/Tec kinases control sustained calcium signaling via site-specific phosphorylation of key residues within the phospholipase C gamma2 SH2-SH3 linker (PMID:15184383)
• SHIP1 and SHIP2 interact preferentially with Tec and inactivate it by de-phosphorylation of local PtdIns 3,4,5-P(3) and inhibition of Tec membrane localization (PMID:15492005)
• Overexpression of Tec is associated with the tumorigenesis and development of liver cancer. (PMID:18171525)
• Tec is the principal kinase of the Tec family that plays a major role in the responses of human neutrophils to monosodium urate crystals, which are likely to be involved in the initiation and perpetuation of gout (PMID:18512796)
• LPS-induced actin polymerization as well as MCP-1, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta expression are dependent on Tec kinase activity. (PMID:19393603)
• inhibits CD25 expression in human T-lymphocytes (PMID:19883687)
• Tec kinase has a crucial role in regulating FGF2 secretion under various physiological conditions (PMID:20230531)
• results suggest that the oncogenic effect of the t(3;9) translocation may be due to the TFG-TEC chimeric protein and that fusion of the TFG (NTD) to the TEC protein produces a gain-of-function chimeric product (PMID:22581839)
• These results provide the first evidence that Nef interacts with cytoplasmic tyrosine kinases of the Tec family and suggest that Nef provides a mechanistic link between HIV-1 and Itk signaling in the viral life cycle. (PMID:24722985)
• using RNA interference, the identified compounds corroborate the role of Tec kinase in unconventional secretion of FGF2. (PMID:27382052)
• TEC is yet another regulator of FGF2-mediated Human pluripotent stem cells pluripotency and differentiation. (PMID:28631381)
• High TEC expression is associated with the development of Mallory Denk Bodies in balloon cells in alcoholic hepatitis. (PMID:28935395)
• Tec may mediate the production and release of pro-inflammatory cytokine IL-8 from human alveolar epithelial cells A549 induced by LPS via the p38 MAPK and ERK MAPK signal pathways. (PMID:31474037)
• TEC kinase stabilizes PLK4 to promote liver cancer metastasis. (PMID:34637843)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tec	ENSDARG00000098477
mus_musculus	Tec	ENSMUSG00000029217
rattus_norvegicus	Tec	ENSRNOG00000002278

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), 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), 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 Tec — P42680 (reviewed: P42680)

All UniProt accessions (3): P42680, D6RB05, D6RB75

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC also regulates FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 ‘Tyr-215’. May also be involved in the regulation of osteoclast differentiation.

Subunit / interactions. Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with CD28, FASLG, FGF2, GRB10, LYN and KIT. Interacts with VAV1 and JAK2.

Subcellular location. Cytoplasm. Cell membrane. Cytoskeleton.

Tissue specificity. Expressed in a wide range of cells, including hematopoietic cell lines like myeloid, B-, and T-cell lineages.

Post-translational modifications. Following B-cell or T-cell receptors engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-519. Undergoes also tyrosine phosphorylation during platelet activation.

Activity regulation. Activated by tyrosine phosphorylation by a wide range of cytokine stimulations. When T-cells or B-cells receptors are activated, a series of phosphorylation leads to the recruitment of TEC to the cell membrane, where it is phosphorylated at Tyr-519. Also activated in response to SCF. Integrin engagement induces tyrosine phosphorylation of TEC in platelets. STAP1 participates in a positive feedback loop by increasing the activity of TEC. SOCS1 is an inhibitor of TEC kinase activity.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain. The SH3 domain is essential for its targeting to activated CD28 costimulatory molecule.

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

RefSeq proteins (1): NP_003206* (*=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
IPR001562	Znf_Btk_motif	Conserved_site
IPR001849	PH_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035572	Tec_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF00169, PF00779, 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 (35 total): strand 13, binding site 6, domain 4, modified residue 3, sequence variant 2, helix 2, chain 1, sequence conflict 1, zinc finger region 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LUL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42680-F1	85.48	0.56

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): 489 (proton acceptor)

Ligand- & substrate-binding residues (6): 133; 143; 376–384; 398; 121; 132

Post-translational modifications (3): 206, 228, 519

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-2871809	FCERI mediated Ca+2 mobilization
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 266 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GCANCTGNY_MYOD_Q6, GOBP_PLATELET_ACTIVATION, AREB6_03, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_WOUND_HEALING, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GCM_RING1, SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (9): adaptive immune response (GO:0002250), protein phosphorylation (GO:0006468), integrin-mediated signaling pathway (GO:0007229), regulation of platelet activation (GO:0010543), intracellular signal transduction (GO:0035556), tissue regeneration (GO:0042246), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), immune system process (GO:0002376)

GO Molecular Function (12): non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Immune System	2
Signaling by Receptor Tyrosine Kinases	1
Fc epsilon receptor (FCERI) signaling	1
Signaling by Interleukins	1
Innate Immune System	1
Cytokine Signaling in Immune system	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
antigen receptor-mediated signaling pathway	2
binding	2
immune response	1
phosphorylation	1
protein modification process	1
cell surface receptor signaling pathway	1
platelet activation	1
regulation of cell activation	1
signal transduction	1
regeneration	1
developmental growth	1
biological_process	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lipid binding	1
transition metal ion 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
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TEC	BLNK	Q8WV28	493
TEC	DOK2	O60496	487
TEC	MTFR1	Q15390	460
TEC	CPQ	Q9Y646	448
TEC	ADAM9	Q13443	443
TEC	TNFRSF11A	Q9Y6Q6	423
TEC	SOCS1	O15524	401
TEC	PIK3C2G	O75747	398
TEC	STAP1	Q9ULZ2	393
TEC	ALG1L2	C9J202	382
TEC	DOK1	Q99704	378
TEC	PIK3R4	Q99570	369
TEC	NFXL1	Q6ZNB6	367
TEC	ANKRD24	Q8TF21	359
TEC	LYN	P07948	341

IntAct

48 interactions, top by confidence:

A	B	Type	Score
ADAM8	TEC	psi-mi:“MI:0407”(direct interaction)	0.560
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
ADAM9	TEC	psi-mi:“MI:0407”(direct interaction)	0.440
ADAM15	TEC	psi-mi:“MI:0407”(direct interaction)	0.440
ADAM19	TEC	psi-mi:“MI:0407”(direct interaction)	0.440
FASLG	TEC	psi-mi:“MI:0407”(direct interaction)	0.440
PRRG4	TEC	psi-mi:“MI:0407”(direct interaction)	0.440
TEC	K15-M	psi-mi:“MI:0407”(direct interaction)	0.440
TEC	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
ASAP1	TEC	psi-mi:“MI:0407”(direct interaction)	0.440
TEC	GAB1	psi-mi:“MI:0407”(direct interaction)	0.440
TEC	KIT	psi-mi:“MI:0407”(direct interaction)	0.440
TEC	MET	psi-mi:“MI:0407”(direct interaction)	0.440
TEC	H1-0	psi-mi:“MI:0915”(physical association)	0.400
MED28	TEC	psi-mi:“MI:0915”(physical association)	0.400
TEC	WAS	psi-mi:“MI:0915”(physical association)	0.400
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
	PLK4	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
	SGK1	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
	PAK4	psi-mi:“MI:0914”(association)	0.350
TEC	SEC16A	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): TEC (Co-fractionation), TEC (Affinity Capture-MS), TEC (Biochemical Activity), TEC (Reconstituted Complex), TEC (Affinity Capture-MS), TEC (Affinity Capture-Western), PRLR (Affinity Capture-Western), VAV1 (Affinity Capture-Western), TEC (Reconstituted Complex), TEC (Phenotypic Enhancement), TEC (Affinity Capture-Western), TEC (Affinity Capture-Western), PIK3R2 (Two-hybrid), LYN (Affinity Capture-Western), KIT (Affinity Capture-Western)

ESM2 similar proteins: A0A2I0BVG8, A0A509AHB6, A0A509AKL0, A5K0N4, A8X6H1, A8X6H4, A8XNJ6, O15865, O61267, O64629, O94737, P05130, P07278, P09215, P21901, P23298, P24723, P28867, P42680, P54644, P62343, P62344, P62345, P81900, P90980, Q05655, Q13237, Q26619, Q2PJ68, Q54CY9, Q54QB1, Q55GV3, Q5BKK4, Q5F3L1, Q5PU49, Q61410, Q64595, Q64617, Q6GLY8, Q6GPN6

Diamond homologs: A0A2R6XIK6, A2VDU3, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, F4JTP5, G5EE56, O01700, O22558, O35346, O43283, O43318, O64768, P08630, P0C8E4, P0CD62, P18106, P18160, P18161, P29317, P32577, P34152, P41239, P41240, P41241, P42680, P42686, P42690, P51813, P80192, P97504, Q00944, Q02779, Q02977, Q03145, Q05397, Q05609, Q0VBZ0

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
TEC	“up-regulates activity”	BMX	phosphorylation
TEC	“down-regulates activity”	BTK	phosphorylation
TEC	“up-regulates activity”	STAP1	phosphorylation
STAP1	“up-regulates activity”	TEC	binding
TEC	“up-regulates activity”	MAF	phosphorylation
SRC	“up-regulates activity”	TEC	phosphorylation
BTK	up-regulates	TEC	phosphorylation
ITK	up-regulates	TEC	phosphorylation
TEC	up-regulates	BMX	phosphorylation
TEC	up-regulates	TEC	phosphorylation
9-(1-Methyl-4-pyrazolyl)-1-[1-(1-oxoprop-2-enyl)-2,3-dihydroindol-6-yl]-2-benzo[h][1,6]naphthyridinone	“down-regulates activity”	TEC	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
Constitutive Signaling by Aberrant PI3K in Cancer	5	17.6×	5e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	13.4×	1e-03
PIP3 activates AKT signaling	6	11.1×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	5	25.2×	8e-04
positive regulation of MAPK cascade	6	11.0×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — ESCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	50
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3065697	NM_003215.3(TEC):c.496-1G>A	Likely pathogenic

SpliceAI

3822 predictions. Top by Δscore:

Variant	Effect	Δscore
4:48137370:T:TA	donor_gain	1.0000
4:48137374:T:TA	donor_gain	1.0000
4:48137418:ATCTT:A	donor_gain	1.0000
4:48137419:T:C	donor_gain	1.0000
4:48138660:TATAC:T	donor_loss	1.0000
4:48138661:ATACC:A	donor_loss	1.0000
4:48138662:TACCT:T	donor_loss	1.0000
4:48138664:C:T	donor_loss	1.0000
4:48138666:T:TA	donor_gain	1.0000
4:48138820:CAC:C	acceptor_gain	1.0000
4:48138822:CCT:C	acceptor_loss	1.0000
4:48138823:CTGG:C	acceptor_loss	1.0000
4:48138824:T:A	acceptor_loss	1.0000
4:48145403:CTT:C	donor_loss	1.0000
4:48145404:TTA:T	donor_loss	1.0000
4:48145405:TA:T	donor_loss	1.0000
4:48145406:A:AC	donor_gain	1.0000
4:48145406:A:AT	donor_loss	1.0000
4:48145407:C:CC	donor_gain	1.0000
4:48145407:C:CG	donor_loss	1.0000
4:48145407:CA:C	donor_gain	1.0000
4:48145407:CAT:C	donor_gain	1.0000
4:48145575:TTTCT:T	acceptor_gain	1.0000
4:48145580:C:CC	acceptor_gain	1.0000
4:48146329:G:C	donor_gain	1.0000
4:48149552:CTTA:C	donor_loss	1.0000
4:48149554:TA:T	donor_loss	1.0000
4:48149555:A:AT	donor_loss	1.0000
4:48149556:CCTG:C	donor_gain	1.0000
4:48149686:CTTCT:C	acceptor_gain	1.0000

AlphaMissense

4187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:48138913:A:G	W549R	1.000
4:48138913:A:T	W549R	1.000
4:48138967:A:G	W531R	1.000
4:48138967:A:T	W531R	1.000
4:48141369:A:C	D507E	1.000
4:48141369:A:T	D507E	1.000
4:48141370:T:A	D507V	1.000
4:48141370:T:C	D507G	1.000
4:48141370:T:G	D507A	1.000
4:48141371:C:G	D507H	1.000
4:48141405:A:C	C495W	1.000
4:48141412:C:A	R493I	1.000
4:48145083:T:A	D489V	1.000
4:48145083:T:C	D489G	1.000
4:48145083:T:G	D489A	1.000
4:48145086:C:A	R488I	1.000
4:48145086:C:G	R488T	1.000
4:48145123:C:A	G476W	1.000
4:48145227:A:T	V441D	1.000
4:48145467:T:A	K398N	1.000
4:48145467:T:G	K398N	1.000
4:48145468:T:A	K398I	1.000
4:48145552:A:G	L370P	1.000
4:48146396:A:G	L337P	1.000
4:48149575:G:C	H330D	1.000
4:48150887:A:T	V283D	1.000
4:48150917:C:A	R273M	1.000
4:48150925:A:C	F270L	1.000
4:48150925:A:T	F270L	1.000
4:48150927:A:G	F270L	1.000

dbSNP variants (sampled 300 via entrez): RS1000047218 (4:48248700 G>A), RS1000050915 (4:48148519 T>G), RS10000735 (4:48186953 C>G,T), RS1000169638 (4:48148898 T>C), RS1000184649 (4:48144821 T>C), RS1000188265 (4:48246242 G>T), RS1000289709 (4:48141397 CTTACTAGACAAT>C), RS1000324644 (4:48142374 G>A), RS1000360231 (4:48233148 G>A,C), RS1000379480 (4:48215705 C>T), RS1000408216 (4:48188726 C>T), RS1000418537 (4:48155780 C>A), RS1000429529 (4:48240046 A>G), RS1000458027 (4:48202393 C>A), RS1000504621 (4:48150489 TC>T)

Disease associations

OMIM: gene MIM:600583 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001729_12	Crohn’s disease	2.000000e-08
GCST002318_51	Rheumatoid arthritis	3.000000e-08
GCST002318_52	Rheumatoid arthritis	1.000000e-07
GCST006959_180	Rheumatoid arthritis	4.000000e-06
GCST006959_85	Rheumatoid arthritis	2.000000e-06
GCST007096_77	Pulse pressure	4.000000e-08
GCST007099_224	Systolic blood pressure	9.000000e-07
GCST009391_714	Metabolite levels	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0010532	salicylurate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4246 (SINGLE PROTEIN), CHEMBL4296642 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

39 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 63,286 (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
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL3707348	ACALABRUTINIB	4	4,504
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL4071161	TIRABRUTINIB	4	2,170
CHEMBL4085457	RITLECITINIB	4	708
CHEMBL5416410	DASATINIB	4	655
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL3545154	POZIOTINIB	3	1,560
CHEMBL3545308	ROCILETINIB	3	1,729
CHEMBL3702854	RILZABRUTINIB	3	851
CHEMBL4072833	EVOBRUTINIB	3	960
CHEMBL4483575	REMIBRUTINIB	3	569
CHEMBL4650321	ORELABRUTINIB	3	364
CHEMBL4650323	TOLEBRUTINIB	3	371
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1922094	APITOLISIB	2	3,070
CHEMBL3301625	SPEBRUTINIB	2	2,965
CHEMBL3900554	BMS-986142	2
CHEMBL402548	DANUSERTIB	2
CHEMBL4094440	BMS-919373	2
CHEMBL4114766	ATUZABRUTINIB	2
CHEMBL4297674	BRANEBRUTINIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL5077961	MILREBRUTINIB	2
CHEMBL5083772	BIIB-091	2
CHEMBL572878	TOZASERTIB	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
PRN694	Inhibition	8.48	pIC50
compound 9 [PMID: 26006010]	Inhibition	8.47	pIC50
nemtabrutinib	Inhibition	8.24	pIC50
compound 38 [PMID: 24915291]	Inhibition	8.2	pIC50
ibrutinib	Inhibition	8.15	pIC50
compound 31 [PMID: 24915291]	Inhibition	8.09	pIC50
ZYBT1	Inhibition	7.6	pIC50
acalabrutinib	Inhibition	7.03	pIC50
compound 25 [PMID: 31260299]	Inhibition	6.64	pIC50
JNJ-64264681	Inhibition	6.52	pIC50

Binding affinities (BindingDB)

52 measured of 52 human assays (52 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
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
9-(1-methylpyrazol-4-yl)-1-(1-prop-2-enoyl-2,3-dihydroindol-6-yl)benzo[h][1,6]naphthyridin-2-one	IC50	6.73 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
N-[5-[9-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,	IC50	7.99 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
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
QL-XII-46	IC50	8.75 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
QL-XII-45	IC50	13 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
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
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
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[3-methyl-1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	290 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-3-yl]pyrazole-4-carboxamide	IC50	300 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-1-(2-but-2-ynoyl-2-azaspiro[3.3]heptan-6-yl)-3-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	500 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
PF-06651600	IC50	606 nM
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[1-[[2-methoxy-5-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	870 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
5-amino-3-[1-[[2-fluoro-3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)pyrazole-4-carboxamide	IC50	1200 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
CI-1033	KD	1700 nM
5-amino-1-(6-but-2-ynoyl-6-azaspiro[3.4]octan-2-yl)-3-[3,5-dimethyl-1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]pyrazole-4-carboxamide	IC50	3000 nM	US-9975882: Heteroaromatic compounds as BTK inhibitors
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM

ChEMBL bioactivities

411 potent at pChembl≥5 of 417 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	CHEMBL5827965
10.05	IC50	0.09	nM	CHEMBL4206765
10.00	IC50	0.1	nM	CHEMBL4217959
9.96	IC50	0.11	nM	CHEMBL4214683
9.92	IC50	0.12	nM	CHEMBL5780981
9.82	IC50	0.15	nM	CHEMBL5948251
9.80	IC50	0.16	nM	CHEMBL4219011
9.80	IC50	0.16	nM	CHEMBL5787507
9.74	IC50	0.18	nM	CHEMBL5872571
9.72	IC50	0.19	nM	CHEMBL5785815
9.72	IC50	0.19	nM	CHEMBL5978552
9.70	IC50	0.2	nM	CHEMBL4207292
9.70	IC50	0.2	nM	CHEMBL5884165
9.64	IC50	0.23	nM	CHEMBL5770715
9.64	IC50	0.23	nM	CHEMBL5872554
9.59	IC50	0.26	nM	CHEMBL5831208
9.55	IC50	0.28	nM	CHEMBL5862546
9.46	IC50	0.35	nM	CHEMBL5840891
9.43	IC50	0.37	nM	CHEMBL5954707
9.42	IC50	0.38	nM	CHEMBL5864688
9.30	IC50	0.5	nM	IBRUTINIB
9.30	IC50	0.5	nM	CHEMBL5189379
9.24	IC50	0.57	nM	IBRUTINIB
9.21	IC50	0.62	nM	CHEMBL4211372
9.21	IC50	0.61	nM	CHEMBL6032578
9.19	IC50	0.64	nM	CHEMBL5839028
9.17	IC50	0.67	nM	CHEMBL4216187
9.13	IC50	0.74	nM	CHEMBL4208358
9.11	IC50	0.78	nM	CHEMBL5947197
9.10	IC50	0.8	nM	RILZABRUTINIB
9.06	IC50	0.87	nM	CHEMBL5892177
9.05	IC50	0.9	nM	CHEMBL4248386
9.05	IC50	0.9	nM	BRANEBRUTINIB
9.01	IC50	0.98	nM	CHEMBL4204572
9.00	Kd	0.99	nM	BRANEBRUTINIB
9.00	Kd	1	nM	IBRUTINIB
8.99	IC50	1.02	nM	CHEMBL5750752
8.96	IC50	1.1	nM	BRANEBRUTINIB
8.96	IC50	1.1	nM	CHEMBL5782207
8.95	IC50	1.13	nM	CHEMBL5946372
8.90	IC50	1.25	nM	CHEMBL5801910
8.90	IC50	1.26	nM	CHEMBL5786077
8.90	IC50	1.27	nM	CHEMBL5929814
8.88	IC50	1.33	nM	CHEMBL5770324
8.88	IC50	1.32	nM	CHEMBL6031448
8.88	IC50	1.31	nM	CHEMBL6064773
8.87	IC50	1.34	nM	MILREBRUTINIB
8.85	IC50	1.4	nM	CHEMBL4211949
8.85	IC50	1.41	nM	CHEMBL5804575
8.85	IC50	1.43	nM	CHEMBL5944742

PubChem BioAssay actives

211 with measured affinity, of 1072 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
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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0001	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	1384816: Inhibition of TEC (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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0001	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	1384816: Inhibition of TEC (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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0002	uM
Ibrutinib	1375526: Inhibition of recombinant human TEC using Poly(Glu, Tyr) 4:1 as substrate after 1 hr by ELISA	ic50	0.0005	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	1850195: Inhibition of TEC (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0005	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0006	uM
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	0.0007	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0007	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0007	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	1850251: Inhibition of TEC (unknown origin) using peptide substrate in presence of ATP	ic50	0.0008	uM
4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide	1656252: Inhibition of TEC (unknown origin)	ic50	0.0009	uM
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide	1399233: Inhibition of TEC (unknown origin)	ic50	0.0009	uM
5-(1,1-difluoroethyl)-N-[1-(6-prop-2-enoyl-6-azaspiro[3.4]octan-2-yl)benzimidazol-2-yl]thiophene-2-carboxamide	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0010	uM
2-[3-[2-amino-6-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one	1830228: Inhibition of human TEC (359 - 631 residues) expressed in baculovirus expression system by mobility shift assay	ic50	0.0013	uM
N-[(7S)-4-amino-6-methylidene-5-(4-phenoxyphenyl)-7,8-dihydropyrimido[5,4-b]pyrrolizin-7-yl]prop-2-enamide	1375526: Inhibition of recombinant human TEC using Poly(Glu, Tyr) 4:1 as substrate after 1 hr by ELISA	ic50	0.0014	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0016	uM
Zanubrutinib	1948214: Inhibition of TEC (unknown origin) 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	0.0017	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0018	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	1850195: Inhibition of TEC (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0019	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0020	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0020	uM
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399233: Inhibition of TEC (unknown origin)	ic50	0.0023	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0023	uM
2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948214: Inhibition of TEC (unknown origin) 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	0.0025	uM
2-[4-(2,4-difluorophenoxy)phenyl]-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948214: Inhibition of TEC (unknown origin) 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	0.0029	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	1678392: Inhibition of TEC (unknown origin)	ic50	0.0030	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0031	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0032	uM
(7S)-7-(1-but-2-ynoylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948214: Inhibition of TEC (unknown origin) 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	0.0036	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0043	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	1384816: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay	ic50	0.0045	uM
1-[4-[[[6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl]amino]methyl]piperidin-1-yl]prop-2-en-1-one	1560824: Binding affinity to DNA-tagged recombinant TEC (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis	kd	0.0045	uM
(Z)-2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile	1850195: Inhibition of TEC (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0045	uM
2-(3-chloro-4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948214: Inhibition of TEC (unknown origin) 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	0.0051	uM
1-[(3S)-3-[6-amino-7-(4-phenoxyphenyl)-8H-purin-9-yl]pyrrolidin-1-yl]but-2-yn-1-one	1939126: Inhibition of TEC (unknown origin)	ic50	0.0053	uM
6-amino-9-[(3R)-1-but-2-ynoylpiperidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one	1357748: Inhibition of TEC (unknown origin)	ic50	0.0053	uM
Acalabrutinib	1878121: Binding affinity to TEC (unknown origin) assessed as dissociation constant by KINOMEscan analysis	kd	0.0055	uM
6-cyclopropyl-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(4-methylpiperazin-1-yl)-2-pyridinyl]amino]-6-oxo-3-pyridinyl]phenyl]isoquinolin-1-one	1763497: Inhibition of human TEC	ic50	0.0057	uM
2-(3-methoxy-4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948214: Inhibition of TEC (unknown origin) 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	0.0059	uM
6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one	1425193: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0060	uM
6-amino-9-[(3R)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one	1560824: Binding affinity to DNA-tagged recombinant TEC (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis	kd	0.0062	uM
N-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	1357748: Inhibition of TEC (unknown origin)	ic50	0.0062	uM
2-methyl-N-[2-[3-[[2-(prop-2-enoylamino)acetyl]amino]anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1155507: Inhibition of Tec (unknown origin) after 1 hr by HTRF assay	ic50	0.0063	uM
2,3-dimethyl-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-1H-indole-7-carboxamide	1399233: Inhibition of TEC (unknown origin)	ic50	0.0064	uM
4-amino-3-(4-phenoxyphenyl)-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]imidazo[4,5-c]pyridin-2-one	1948242: Inhibition of FLAG-tagged TEC autophosphorylation in HEK293 cells incubated for 2 hrs by MSD electrochemiluminescence immunoassay	ic50	0.0078	uM
2-methyl-N-[2-[3-(prop-2-enoylamino)anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1155507: Inhibition of Tec (unknown origin) after 1 hr by HTRF assay	ic50	0.0082	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	1319784: Inhibition of TEC (unknown origin)	ic50	0.0100	uM
2-(3-hydroxy-4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1948214: Inhibition of TEC (unknown origin) 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	0.0110	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Dasatinib	affects binding, decreases activity	2
Aflatoxin B1	decreases methylation, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
honokiol	affects localization, decreases reaction	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
AG 1879	affects localization, decreases reaction	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
N-Formylmethionine Leucyl-Phenylalanine	affects localization, decreases reaction	1
Phthalic Acids	increases methylation	1
Valproic Acid	increases expression, affects cotreatment	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

302 unique, capped per target: 291 binding, 11 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043826	Binding	Residual activity of TEC at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL4020208	ADMET	Inhibition of human TEC using poly[Glu:Tyr] as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition by filter binding method	In Silico Identification of a Novel Hinge-Binding Scaffold for Kinase Inhibitor Discovery. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1QX	Abcam K-562 TEC KO	Cancer cell line	Female
CVCL_D2MI	Abcam Raji TEC KO	Cancer cell line	Male
CVCL_TR87	HAP1 TEC (-)	Cancer cell line	Male
CVCL_WQ66	Abcam Jurkat TEC KO	Cancer cell line	Male

Clinical trials (associated diseases)

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