BTK

Summary

BTK (Bruton tyrosine kinase, HGNC:1133) is a protein-coding gene on chromosome Xq22.1, encoding Tyrosine-protein kinase BTK (Q06187). Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. In precision oncology, BTK C481S is associated with resistance to Ibrutinib in Chronic Lymphocytic Leukemia (CIViC Level B); 1 further curated variant–drug associations are listed below. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene plays a crucial role in B-cell development. Mutations in this gene cause X-linked agammaglobulinemia type 1, which is an immunodeficiency characterized by the failure to produce mature B lymphocytes, and associated with a failure of Ig heavy chain rearrangement. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 695 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bruton-type agammaglobulinemia (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 976 total — 254 pathogenic, 99 likely-pathogenic
• Phenotypes (HPO): 77
• Druggable target: yes — 84 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1133
Approved symbol	BTK
Name	Bruton tyrosine kinase
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	ATK, XLA, PSCTK1
Ensembl gene	ENSG00000010671
Ensembl biotype	protein_coding
OMIM	300300
Entrez	695

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 20 protein_coding, 8 nonsense_mediated_decay, 7 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000308731, ENST00000464006, ENST00000464567, ENST00000470069, ENST00000470329, ENST00000478995, ENST00000488970, ENST00000621635, ENST00000695614, ENST00000695615, ENST00000695616, ENST00000695617, ENST00000695618, ENST00000695619, ENST00000695620, ENST00000695621, ENST00000695622, ENST00000695623, ENST00000695624, ENST00000695625, ENST00000695626, ENST00000695627, ENST00000695628, ENST00000695629, ENST00000695630, ENST00000695631, ENST00000695632, ENST00000695633, ENST00000695634, ENST00000695643, ENST00000703407, ENST00000896540, ENST00000914420, ENST00000944955, ENST00000944956, ENST00000944957, ENST00000944958

RefSeq mRNA: 3 — MANE Select: NM_000061 NM_000061, NM_001287344, NM_001287345

CCDS: CCDS14482, CCDS76002, CCDS76003

Canonical transcript exons

ENST00000308731 — 19 exons

Exon	Start	End
ENSE00000673977	101354630	101354694
ENSE00000673980	101356052	101356268
ENSE00000673981	101356784	101356955
ENSE00000673983	101358310	101358437
ENSE00000673984	101358617	101358696
ENSE00001601394	101362173	101362240
ENSE00001608013	101360568	101360755
ENSE00001643950	101374536	101374634
ENSE00001643964	101362561	101362689
ENSE00001646803	101371633	101371701
ENSE00001698702	101369998	101370079
ENSE00001702496	101353194	101353351
ENSE00001712685	101360088	101360150
ENSE00001780523	101353870	101353988
ENSE00001801955	101359293	101359347
ENSE00003624587	101357509	101357583
ENSE00003964492	101386062	101386191
ENSE00003964497	101349450	101349956
ENSE00003964522	101375144	101375314

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 98.10.

FANTOM5 (CAGE): breadth broad, TPM avg 14.9984 / max 819.2627, expressed in 579 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199951	14.8837	565
199949	0.0817	40
199948	0.0331	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.10	gold quality
mononuclear cell	CL:0000842	97.81	gold quality
leukocyte	CL:0000738	97.70	gold quality
granulocyte	CL:0000094	97.46	gold quality
spleen	UBERON:0002106	94.99	gold quality
bone marrow cell	CL:0002092	94.27	gold quality
lymph node	UBERON:0000029	93.86	gold quality
blood	UBERON:0000178	93.63	gold quality
vermiform appendix	UBERON:0001154	93.36	gold quality
epithelium of nasopharynx	UBERON:0001951	92.24	gold quality
nasopharynx	UBERON:0001728	92.22	gold quality
bone marrow	UBERON:0002371	91.17	gold quality
type B pancreatic cell	CL:0000169	89.64	gold quality
caecum	UBERON:0001153	89.62	gold quality
right lung	UBERON:0002167	89.61	gold quality
olfactory bulb	UBERON:0002264	89.33	gold quality
upper lobe of left lung	UBERON:0008952	87.93	gold quality
upper lobe of lung	UBERON:0008948	87.00	gold quality
rectum	UBERON:0001052	86.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.46	gold quality
gall bladder	UBERON:0002110	85.29	gold quality
smooth muscle tissue	UBERON:0001135	84.28	gold quality
colonic epithelium	UBERON:0000397	84.21	gold quality
trabecular bone tissue	UBERON:0002483	83.77	gold quality
superficial temporal artery	UBERON:0001614	83.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.25	gold quality
small intestine	UBERON:0002108	83.02	gold quality
right coronary artery	UBERON:0001625	82.77	gold quality
spinal cord	UBERON:0002240	81.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.45	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.38
E-MTAB-6701	yes	11.43
E-ANND-3	yes	11.34
E-CURD-112	yes	11.23
E-CURD-122	yes	8.83
E-HCAD-10	yes	6.97
E-MTAB-9801	yes	5.49
E-MTAB-7381	no	393.65
E-MTAB-7303	no	82.64
E-MTAB-6678	no	3.98
E-MTAB-5061	no	3.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, BCL11B, CEBPB, CEBPG, EGR2, EGR3, FOS, GTF2I, GTF3A, HMGA1, IRF6, JUN, KAT7, KDM5D, MAF, NFKB, NKX2-1, NOTO, NR4A3, NR5A1, POU2F2, REL, SP1, SP3, SPI1, SPIB, TBP, TBX21, TXK

miRNA regulators (miRDB)

32 targeting BTK, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-24-1-5P	95.57	65.85	492
HSA-MIR-24-2-5P	95.57	66.16	484

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Authors showed that human Btk kinase-/SH2 domain mutants, expressed in Btk-deficient DT40 cell line, inhibit Hydrogen Peroxide-induced Tyrosine phosphorylation of PLCG2; this phosphorylation is restored by intact/wild-type (human) Btk. PH domain mutant (PMID:11434777)
• Btk deficiency results in significantly impaired hydrogen peroxide-induced calcium signaling and reduced tyrosine phosphorylation of phospholipase Cgamma2 in cultured cells. (PMID:11434777)
• In hydrogen peroxide-stimulated DT40 cells, BLNK is phosphorylated by Syk and not by Btk. (PMID:11434777)
• mutational analysis in Spanish X linked agammaglobulinemia patients (PMID:11438999)
• Direct stimulation of Bruton’s tyrosine kinase by G protein alpha subunits (PMID:11665629)
• mutations in Turkish patients with presumed X-linked agammaglobulinemia (PMID:11668622)
• changes in the local concentration of Btk itself, or co-localization with exogenous signaling molecules that have high affinity for either proline sequence or the SH3 domain, can significantly alter species composition and regulate Btk kinase activity (PMID:11742120)
• Interaction of Bruton’s tyrosine kinase and protein kinase Ctheta in platelets (PMID:11788586)
• Interaction between Btk TH and SH3 domain (PMID:11877742)
• A total of 391 genes were found to be differentially expressed in BTK(-)cells, including kinases and transcriptions factors. Furthermore, one expressed sequence tag and eight complementary DNA clones with unknown function were down-regulated. (PMID:11920564)
• Review article on X-linked agammaglobulinemia. The BTK gene is the primary defect in this disease. (PMID:12001708)
• Flow cytometry revealed deficient expression of BTK protein in 10 of the 13 families, and this is the first report of the diagnosis of XLA by analysis of mutations of the BTK gene in Brazilian patients. (PMID:12204007)
• the presence of wild-type BTK transcripts can be one of the many factors that influence the clinical and immunological phenotype in X-linked agammaglobulinemia. (PMID:12405164)
• CD40 is a surface receptor through which the activity of Btk can be stimulated in human B cells. (PMID:12437073)
• Btk is a Toll/interleukin-1 receptor domain-binding protein that is important for NFkappaB activation by TLR4 (PMID:12724322)
• Mutations were identified in BTK including a novel sequence deletion. (PMID:12768435)
• Data show that overexpression of Bruton’s tyrosine kinase results in the stabilization of tumor necrosis factor alpha mRNA via the 3’ untranslated region. (PMID:12810683)
• Defective expression of Bruton’s tyrosine kinase in acute lymphoblastic leukemia in infants. (PMID:12854903)
• results indicate that, contrary to Src and Abl, Btk might not require an assembled conformation for the regulation of its activity (PMID:12970174)
• Conclusion of Btk transgene study is that autophosphorylation at residue Y223 is not essential for Btk function in vivo except for regulation of lambda light chain usage; and Btk partially acts as an adapter molecule independent of its catalytic activity. (PMID:14634110)
• Twenty-two novel mutations including one large deletion comprising the coding sequence from exon 11 to 18 in European X-linked agammaglobulinemia patients. (PMID:14974089)
• Conservation and covariance in mutations of BTK domain sequences causing agammaglobulinemia were studied. (PMID:15082835)
• Btk is essential in regulating thresholds for human B cell tolerance. (PMID:15466623)
• 2 insertions, an SVA element and an AluY sequence, occurred 12 bp before the end of exon 9. Both had the typical hallmarks of a retrotransposon insertion including target site duplication and a long poly A tail. (PMID:15712380)
• required for the signaling pathway activated by TLR4, which culminates in phosphorylation of p65 on serine 536 promoting transactivation by NFkappaB (PMID:15849198)
• Ca2+-independent activation of Bruton’s tyrosine kinase is required for store-mediated Ca2+ entry in human platelets (PMID:15894173)
• lack of BTK expression or expression of dominant-negative splice variants in B cell precursor leukemia cells can (i) inhibit differentiation beyond the pre-B cell stage and (ii) protect from radiation-induced apoptosis (PMID:16141323)
• Review summarizes how activated Btk transmits survival signals that are essential for the transforming activity of oncogenic Abl tyrosine kinase. (PMID:16300960)
• Mal phosphorylation has an effect on tyrosine during signaling by TLR2 and TLR4 and Btk is the kinase involved (PMID:16439361)
• data provide evidence for a common requirement for Btk in toll-like receptor 2 (TLR2)- and TLR4-mediated induction of two important proinflammatory cytokines, TNF and IL-1beta (PMID:16517732)
• Btk is not essential for early lipopolysaccharide signaling in human monocytes. (PMID:16751014)
• splice mutations of the BTK gene may have roles in X-linked agammaglobulinemia (PMID:16951917)
• analysis of BTK activation mechanism and steady state kinetics (PMID:17264076)
• A first report of an X-linked Agammaglobulinemia patient with a polymorphism in Btk SH3 domain has been identified after sequencing of the entire gene. (PMID:17707910)
• Most of mutations were located at the kinase domain of Btk and, less frequently, they were found in PH and SH2 domains. Protein expression was also affected since most of the patients did not express or express very low Btk. (PMID:17765309)
• Btk as a key signaling molecule that interacts with and acts downstream of TLR8 and TLR9. (PMID:17932028)
• Plasmacytoid dendritic cells express a signalosome consisting of Lyn, Syk, Btk, Slp65 (Blnk) and PLCgamma2. (PMID:18022864)
• Of 9 CVID patients from a single Taiwanese tertiary care hospital, we identified 2 cousins with decreased Btk expression who had a mutated (Asp521Val) kinase domain of Btk (1694A>T in exon 15) (PMID:18051214)
• results suggest that none of the X-linked agammaglobulinaemia-associated Btk mutants with significant protein expression have a dominant negative effect over wild type Btk function (PMID:18241233)
• Bruton’s tyrosine kinase is not essential for Bcr-Abl-mediated transformation of lymphoid or myeloid cells. (PMID:18548107)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	btk	ENSDARG00000004433
mus_musculus	Btk	ENSMUSG00000031264
rattus_norvegicus	Btk	ENSRNOG00000052407

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), 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), 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 BTK — Q06187 (reviewed: Q06187)

Alternative names: Agammaglobulinemia tyrosine kinase, B-cell progenitor kinase, Bruton tyrosine kinase

All UniProt accessions (18): Q06187, A0A8Q3SHX9, A0A8Q3SHZ6, A0A8Q3SI35, A0A8Q3SI38, A0A8Q3SI44, A0A8Q3WKM0, A0A8Q3WKN1, A0A8Q3WKR7, A0A8Q3WKS7, A0A8Q3WL62, A0A8Q3WLR2, A0A8Q3WLZ5, Q3MS88, Q3MS90, Q3MS94, Q3MS97, Q5JY90

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK also plays a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41.

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. Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9. Interacts with MPL/TPOR.

Subcellular location. Cytoplasm. Cell membrane. Nucleus. Membrane raft.

Tissue specificity. Predominantly expressed in B-lymphocytes.

Post-translational modifications. Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-551 by LYN and SYK. Phosphorylation at Tyr-551 is followed by autophosphorylation of Tyr-223 which may create a docking site for a SH2 containing protein. Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction. Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes its recruitment.

Disease relevance. X-linked agammaglobulinemia (XLA) [MIM:300755] Humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin. The disease is caused by variants affecting the gene represented in this entry. Growth hormone deficiency, isolated, 3, with agammaglobulinemia (IGHD3) [MIM:307200] An X-linked recessive disorder characterized by growth hormone deficiency, short stature, delayed bone age, agammaglobulinemia with markedly reduced numbers of B cells, and good response to treatment with growth hormone. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by phosphorylation. In primary B lymphocytes, is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug acting as a tyrosine kinase inhibitor, also blocks BTK 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.

Miscellaneous. Produced by alternative promoter usage. Predominant form in many tumor cells where it may function as an anti-apoptotic cell survival factor.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q06187-1	BTK-A	yes
Q06187-2	BTK-C

RefSeq proteins (3): NP_000052, NP_001274273, NP_001274274 (=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
IPR035574	BTK_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 (236 total): sequence variant 117, strand 38, helix 21, modified residue 15, binding site 13, turn 11, mutagenesis site 8, domain 4, region of interest 2, initiator methionine 1, chain 1, active site 1, sequence conflict 1, splice variant 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

156 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5P9J	X-RAY DIFFRACTION	1.08
6DI1	X-RAY DIFFRACTION	1.1
5P9I	X-RAY DIFFRACTION	1.11
6HRP	X-RAY DIFFRACTION	1.12
6E4F	X-RAY DIFFRACTION	1.15
4RFZ	X-RAY DIFFRACTION	1.17
7L5O	X-RAY DIFFRACTION	1.21
5P9L	X-RAY DIFFRACTION	1.25
6DI9	X-RAY DIFFRACTION	1.25
6J6M	X-RAY DIFFRACTION	1.25
7N5O	X-RAY DIFFRACTION	1.25
5P9K	X-RAY DIFFRACTION	1.28
6BLN	X-RAY DIFFRACTION	1.3
6DI0	X-RAY DIFFRACTION	1.3
8FLV	X-RAY DIFFRACTION	1.3
5U9D	X-RAY DIFFRACTION	1.33
7KXM	X-RAY DIFFRACTION	1.33
8FLN	X-RAY DIFFRACTION	1.33
6X3P	X-RAY DIFFRACTION	1.34
7KXN	X-RAY DIFFRACTION	1.34
4RX5	X-RAY DIFFRACTION	1.36
6HRT	X-RAY DIFFRACTION	1.36
6TT2	X-RAY DIFFRACTION	1.36
7KXQ	X-RAY DIFFRACTION	1.38
5KUP	X-RAY DIFFRACTION	1.39
6NFH	X-RAY DIFFRACTION	1.4
6VXQ	X-RAY DIFFRACTION	1.4
7YC9	X-RAY DIFFRACTION	1.4
5P9M	X-RAY DIFFRACTION	1.41
6OMU	X-RAY DIFFRACTION	1.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06187-F1	84.95	0.52

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): 521 (proton acceptor)

Ligand- & substrate-binding residues (13): 26; 28; 39; 53; 143; 154; 155; 165; 408–416; 430; 474–477; 474–477 …

Post-translational modifications (15): 2, 21, 40, 55, 115, 180, 191, 223, 344, 361, 551, 604, 617, 623, 659

Mutagenesis-validated functional residues (8):

Position	Phenotype
41	no effect on phosphorylation of gtf2i.
189	no effect on phosphorylation of gtf2i.
223	loss of phosphorylation of gtf2i.
251–252	large decrease in binding by sh3bp5.
251	no effect on phosphorylation of gtf2i.
307	loss of phosphorylation of gtf2i.
551	loss of phosphorylation of gtf2i.
617	defective in mediating calcium response.

Function

Pathways and Gene Ontology

Reactome pathways

45 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-2424491	DAP12 signaling
R-HSA-2871809	FCERI mediated Ca+2 mobilization
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-8964315	G beta:gamma signalling through BTK
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2172127	DAP12 interactions
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling

MSigDB gene sets: 682 (showing top): PID_BCR_5PATHWAY, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, AP1_01, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (50): neutrophil homeostasis (GO:0001780), positive regulation of type III hypersensitivity (GO:0001805), positive regulation of type I hypersensitivity (GO:0001812), adaptive immune response (GO:0002250), B cell affinity maturation (GO:0002344), histamine secretion by mast cell (GO:0002553), positive regulation of immunoglobulin production (GO:0002639), regulation of B cell cytokine production (GO:0002721), MyD88-dependent toll-like receptor signaling pathway (GO:0002755), regulation of B cell apoptotic process (GO:0002902), mesoderm development (GO:0007498), peptidyl-tyrosine phosphorylation (GO:0018108), calcium-mediated signaling (GO:0019722), proteoglycan catabolic process (GO:0030167), negative regulation of B cell proliferation (GO:0030889), positive regulation of B cell proliferation (GO:0030890), response to lipopolysaccharide (GO:0032496), negative regulation of interleukin-10 production (GO:0032693), positive regulation of interleukin-6 production (GO:0032755), positive regulation of tumor necrosis factor production (GO:0032760), cellular response to reactive oxygen species (GO:0034614), intracellular signal transduction (GO:0035556), Fc-epsilon receptor signaling pathway (GO:0038095), B cell activation (GO:0042113), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), positive regulation of B cell differentiation (GO:0045579), cell maturation (GO:0048469), positive regulation of phagocytosis (GO:0050766), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), monocyte proliferation (GO:0061516), cellular response to molecule of fungal origin (GO:0071226), apoptotic signaling pathway (GO:0097190), cellular response to interleukin-7 (GO:0098761), positive regulation of cGAS/STING signaling pathway (GO:0141111), positive regulation of interleukin-17A production (GO:0150153), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), positive regulation of synoviocyte proliferation (GO:1901647)

GO Molecular Function (15): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), zinc ion binding (GO:0008270), phospholipase activator activity (GO:0016004), identical protein binding (GO:0042802), phospholipase binding (GO:0043274), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
GPCR downstream signalling	2
Diseases associated with the TLR signaling cascade	2
Antigen processing-Cross presentation	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
DAP12 interactions	1
Fc epsilon receptor (FCERI) signaling	1
RHO GTPase Effectors	1
G-protein beta:gamma signalling	1
Leishmania phagocytosis	1
SARS-CoV Infections	1
Signaling by the B Cell Receptor (BCR)	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
positive regulation of hypersensitivity	2
positive regulation of immunoglobulin mediated immune response	2
regulation of B cell proliferation	2
B cell proliferation	2
binding	2
leukocyte homeostasis	1
myeloid cell homeostasis	1
type III hypersensitivity	1
regulation of type III hypersensitivity	1
positive regulation of myeloid leukocyte mediated immunity	1
regulation of type I hypersensitivity	1
type I hypersensitivity	1
immune response	1
peripheral B cell selection	1
immunoglobulin production involved in immunoglobulin-mediated immune response	1
histamine secretion involved in inflammatory response	1
mast cell degranulation	1
establishment of localization in cell	1
exocytic process	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
B cell cytokine production	1
regulation of B cell mediated immunity	1
regulation of cytokine production involved in immune response	1
toll-like receptor signaling pathway	1
B cell apoptotic process	1
regulation of lymphocyte apoptotic process	1
tissue development	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
intracellular signaling cassette	1
proteoglycan metabolic process	1
glycoprotein catabolic process	1
negative regulation of lymphocyte proliferation	1
negative regulation of B cell activation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1

Protein interactions and networks

STRING

4208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTK	BLNK	Q8WV28	998
BTK	PLCG2	P16885	997
BTK	VAV1	P15498	988
BTK	SYK	P43405	987
BTK	LCP2	Q13094	983
BTK	MYD88	P78397	975
BTK	LYN	P07948	961
BTK	GRB2	P29354	958
BTK	CD79B	P40259	927
BTK	CD79A	P11912	907
BTK	GTF2I	P78347	887
BTK	IRAK4	Q9NWZ3	885
BTK	IRAK1	P51617	880
BTK	WAS	P42768	879
BTK	TLR9	Q9NR96	872

IntAct

97 interactions, top by confidence:

A	B	Type	Score
BTK	GTF2I	psi-mi:“MI:0915”(physical association)	0.720
GTF2I	BTK	psi-mi:“MI:0915”(physical association)	0.720
BTK	GTF2I	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
BTK	BLNK	psi-mi:“MI:0407”(direct interaction)	0.670
BLNK	BTK	psi-mi:“MI:0915”(physical association)	0.670
HSP90AB1	BTK	psi-mi:“MI:0915”(physical association)	0.640
BTK		psi-mi:“MI:0915”(physical association)	0.630
	BTK	psi-mi:“MI:0407”(direct interaction)	0.630
	BTK	psi-mi:“MI:0915”(physical association)	0.630
BTK	BTK	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
BTK	BTK	psi-mi:“MI:0407”(direct interaction)	0.620
KATNB1	BTK	psi-mi:“MI:0915”(physical association)	0.590
BTK	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
ADAM15	BTK	psi-mi:“MI:0407”(direct interaction)	0.560
BTK	MAL	psi-mi:“MI:0403”(colocalization)	0.560
MAL	BTK	psi-mi:“MI:0915”(physical association)	0.560
BTK	MAL	psi-mi:“MI:0915”(physical association)	0.560
MAL	BTK	psi-mi:“MI:0403”(colocalization)	0.560

BioGRID (162): MPP7 (Co-fractionation), BTK (Two-hybrid), BECN1 (Two-hybrid), MRPS22 (Two-hybrid), BTK (Biochemical Activity), BTK (Reconstituted Complex), MEOX2 (Two-hybrid), HSP90AB3P (Affinity Capture-MS), ANKRD54 (Affinity Capture-MS), TTC9C (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), BTK (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), ARID3A (Affinity Capture-Western)

ESM2 similar proteins: A8XI74, F1N9Y5, G5ECJ6, O15075, P08487, P08630, P10686, P16885, P19174, P24135, P24604, P35991, P42680, P43403, P43404, P43405, P46108, P46109, P47941, P48025, P51813, P53356, P54936, P87378, Q00655, Q04929, Q06187, Q22070, Q24145, Q45FX5, Q54Y55, Q5U2U2, Q62077, Q62422, Q63768, Q64010, Q64725, Q6P686, Q6TGW5, Q6XJU9

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

49 interactions.

A	Effect	B	Mechanism
BTK	“up-regulates activity”	PLCG2	phosphorylation
BTK	up-regulates	PLCG2	phosphorylation
ibrutinib	down-regulates	BTK	“chemical inhibition”
ABL1	unknown	BTK	phosphorylation
TEC	“down-regulates activity”	BTK	phosphorylation
SYK	“up-regulates activity”	BTK	phosphorylation
PRKCB	“down-regulates activity”	BTK	phosphorylation
SRC	“up-regulates activity”	BTK	phosphorylation
ABL1	“down-regulates activity”	BTK	phosphorylation
BTK	“up-regulates activity”	WAS	phosphorylation
AKT1	“down-regulates quantity by destabilization”	BTK	phosphorylation
GNA12	“up-regulates activity”	BTK	binding
acalabrutinib	“down-regulates activity”	BTK	“chemical inhibition”
BTK	“down-regulates activity”	MDM2	phosphorylation
BTK	“down-regulates activity”	STAT3	phosphorylation
JAK2	“up-regulates activity”	BTK	phosphorylation
BTK	“up-regulates activity”	IKZF1	phosphorylation
BTK	“up-regulates activity”	PLCG1	phosphorylation
BTK	“up-regulates activity”	WIPF1	phosphorylation
BTK	“up-regulates quantity”	CNN3	phosphorylation
BTK	“up-regulates activity”	RELA	phosphorylation
BTK	up-regulates	BTK	phosphorylation
LYN	up-regulates	BTK	phosphorylation
BTK	up-regulates	GTF2I	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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	6	18.6×	1e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	16.5×	9e-05
MAPK1/MAPK3 signaling	5	16.0×	5e-04
MAPK family signaling cascades	5	12.6×	1e-03
PIP3 activates AKT signaling	7	11.4×	2e-04
Diseases of signal transduction by growth factor receptors and second messengers	7	9.7×	4e-04
RAF/MAP kinase cascade	6	8.9×	1e-03
SARS-CoV Infections	5	6.8×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	22.9×	2e-03

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	254
Likely pathogenic	99
Uncertain significance	197
Likely benign	203
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012315	NM_000061.3(BTK):c.1349+1G>A	Pathogenic
1012881	NM_000061.3(BTK):c.1106T>C (p.Leu369Pro)	Pathogenic
1069599	NM_000061.3(BTK):c.62C>A (p.Ser21Ter)	Pathogenic
1071572	NM_000061.3(BTK):c.1379T>A (p.Leu460Ter)	Pathogenic
1071573	NM_000061.3(BTK):c.1102G>T (p.Gly368Ter)	Pathogenic
1072527	NC_000023.10:g.(?100604853)(100609705_?)del	Pathogenic
1072528	NC_000023.10:g.(?100608162)(100615763_?)del	Pathogenic
1075549	NM_000061.3(BTK):c.520+1G>A	Pathogenic
1076964	NM_000061.3(BTK):c.241-1G>C	Pathogenic
11343	NM_000061.3(BTK):c.1288A>G (p.Lys430Glu)	Pathogenic
11344	NM_000061.3(BTK):c.37C>T (p.Arg13Ter)	Pathogenic
11347	NM_000061.3(BTK):c.1750+5G>A	Pathogenic
11348	NM_000061.3(BTK):c.83G>A (p.Arg28His)	Pathogenic
11350	BTK, ALA-ASP, 1952C-A	Pathogenic
11351	NM_000061.3(BTK):c.97A>C (p.Thr33Pro)	Pathogenic
11352	NM_000061.3(BTK):c.228_231del (p.Glu76fs)	Pathogenic
11353	NM_000061.3(BTK):c.141+3_141+4del	Pathogenic
11354	NM_000061.3(BTK):c.310-1G>C	Pathogenic
11355	NM_000061.3(BTK):c.310-2A>G	Pathogenic
11356	NM_000061.3(BTK):c.338T>A (p.Val113Asp)	Pathogenic
11357	NM_000061.3(BTK):c.389del (p.Asn130fs)	Pathogenic
11358	NM_000061.3(BTK):c.557dup (p.Pro187fs)	Pathogenic
11359	NM_000061.3(BTK):c.588_589insCTACATAG (p.Ile197fs)	Pathogenic
11360	NM_000061.3(BTK):c.653del (p.Lys218fs)	Pathogenic
11361	NM_000061.3(BTK):c.718G>T (p.Glu240Ter)	Pathogenic
11362	NM_000061.3(BTK):c.755G>A (p.Trp252Ter)	Pathogenic
11363	NM_000061.3(BTK):c.763C>T (p.Arg255Ter)	Pathogenic
11364	NM_000061.3(BTK):c.839+1G>A	Pathogenic
11365	BTK, 1-BP DEL/3-BP INS, CODON 261	Pathogenic
11367	NM_000061.3(BTK):c.919A>G (p.Arg307Gly)	Pathogenic

SpliceAI

2410 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101353348:ACCC:A	acceptor_gain	1.0000
X:101353349:CCC:C	acceptor_gain	1.0000
X:101353349:CCCC:C	acceptor_gain	1.0000
X:101353350:CC:C	acceptor_gain	1.0000
X:101353350:CCC:C	acceptor_gain	1.0000
X:101353350:CCCTA:C	acceptor_loss	1.0000
X:101353351:CC:C	acceptor_gain	1.0000
X:101353352:C:A	acceptor_loss	1.0000
X:101353352:C:CC	acceptor_gain	1.0000
X:101353353:T:C	acceptor_loss	1.0000
X:101353863:CACTT:C	donor_loss	1.0000
X:101353864:ACTT:A	donor_loss	1.0000
X:101353865:CTTA:C	donor_loss	1.0000
X:101353866:TTA:T	donor_loss	1.0000
X:101353867:T:TG	donor_loss	1.0000
X:101353868:A:AC	donor_gain	1.0000
X:101353869:C:CC	donor_gain	1.0000
X:101354625:CTCA:C	donor_loss	1.0000
X:101354626:TCACC:T	donor_loss	1.0000
X:101354627:CACCT:C	donor_loss	1.0000
X:101354628:A:T	donor_loss	1.0000
X:101354695:C:CC	acceptor_gain	1.0000
X:101356035:T:TA	donor_gain	1.0000
X:101356075:TTG:T	donor_gain	1.0000
X:101356081:C:CA	donor_gain	1.0000
X:101356107:T:TA	donor_gain	1.0000
X:101356778:A:C	donor_gain	1.0000
X:101356779:CTCA:C	donor_loss	1.0000
X:101356780:TCA:T	donor_loss	1.0000
X:101356781:CACAT:C	donor_loss	1.0000

AlphaMissense

4362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101349944:G:T	R641S	1.000
X:101353202:A:G	W634R	1.000
X:101353202:A:T	W634R	1.000
X:101353203:G:C	C633W	1.000
X:101353312:G:T	P597Q	1.000
X:101353313:G:A	P597S	1.000
X:101353321:C:A	G594V	1.000
X:101353321:C:T	G594E	1.000
X:101353322:C:A	G594W	1.000
X:101353340:A:G	W588R	1.000
X:101353340:A:T	W588R	1.000
X:101353351:C:T	G584E	1.000
X:101353870:C:A	G584W	1.000
X:101353870:C:G	G584R	1.000
X:101353870:C:T	G584R	1.000
X:101353879:A:G	W581R	1.000
X:101353879:A:T	W581R	1.000
X:101353884:T:A	D579V	1.000
X:101353884:T:G	D579A	1.000
X:101353885:C:G	D579H	1.000
X:101353887:G:A	S578F	1.000
X:101353895:G:C	S575R	1.000
X:101353895:G:T	S575R	1.000
X:101353897:T:G	S575R	1.000
X:101353898:G:C	F574L	1.000
X:101353898:G:T	F574L	1.000
X:101353900:A:G	F574L	1.000
X:101353931:C:A	W563C	1.000
X:101353931:C:G	W563C	1.000
X:101353932:C:G	W563S	1.000

dbSNP variants (sampled 300 via entrez): RS1000073656 (X:101389238 T>C), RS1000202210 (X:101353784 T>A,C), RS1000295709 (X:101373116 T>C), RS1000424934 (X:101389643 C>T), RS1001066777 (X:101380967 T>C), RS1001289713 (X:101372291 T>G), RS1001346545 (X:101372701 T>C), RS1001446026 (X:101362479 A>G), RS1001604060 (X:101352142 G>A), RS1001833121 (X:101365036 G>A), RS1001903175 (X:101363034 C>T), RS1001993908 (X:101355141 G>A,T), RS1002343335 (X:101354612 T>A), RS1002414117 (X:101388629 G>A), RS1002649670 (X:101350618 C>T)

Disease associations

OMIM: gene MIM:300300 | disease phenotypes: MIM:307200, MIM:300755, MIM:601495, MIM:304700, MIM:607594, MIM:301500

GenCC curated gene-disease

Disease	Classification	Inheritance
Bruton-type agammaglobulinemia	Definitive	X-linked
isolated growth hormone deficiency type III	Strong	X-linked
short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia	Supportive	X-linked

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
isolated growth hormone deficiency type III	Disputed	XL
Bruton-type agammaglobulinemia	Definitive	XL

Mondo (8): isolated growth hormone deficiency type III (MONDO:0010615), Bruton-type agammaglobulinemia (MONDO:0010421), autosomal recessive agammaglobulinemia 1 (MONDO:0020729), deafness dystonia syndrome (MONDO:0010578), common variable immunodeficiency (MONDO:0015517), Fabry disease (MONDO:0010526), diffuse large B-cell lymphoma (MONDO:0018905), short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia (MONDO:0018967)

Orphanet (8): Isolated growth hormone deficiency type III (Orphanet:231692), Non-acquired isolated growth hormone deficiency (Orphanet:631), Non-syndromic agammaglobulinemia (Orphanet:229717), X-linked agammaglobulinemia (Orphanet:47), Mohr-Tranebjaerg syndrome (Orphanet:52368), OBSOLETE: Common variable immunodeficiency (Orphanet:1572), Fabry disease (Orphanet:324), Diffuse large B-cell lymphoma (Orphanet:544)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000024	Prostatitis
HP:0000031	Epididymitis
HP:0000162	Glossoptosis
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000509	Conjunctivitis
HP:0000750	Delayed speech and language development
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000988	Skin rash
HP:0000999	Pyoderma
HP:0001053	Hypopigmented skin patches
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001402	Hepatocellular carcinoma
HP:0001412	Enteroviral hepatitis
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001648	Cor pulmonale
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001903	Anemia
HP:0001945	Fever
HP:0002014	Diarrhea

GWAS associations

0 associations (top):

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D017074	Common Variable Immunodeficiency	C20.673.330
D000795	Fabry Disease	C10.228.140.163.100.435.825.200; C10.228.140.300.275.374; C14.907.253.329.374; C16.320.322.124; C16.320.565.189.435.825.200; C16.320.565.398.641.803.300; C16.320.565.595.554.825.200; C18.452.132.100.435.825.200; C18.452.584.563.641.803.300; C18.452.648.189.435.825.200; C18.452.648.398.641.803.300; C18.452.648.595.554.825.200
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
C537409	Bruton type agammaglobulinemia (supp.)
C537149	Hypogammaglobulinemia and Isolated growth hormone deficiency, X-linked (supp.)
C535808	Mohr-Tranebjaerg syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL4296642 (PROTEIN FAMILY), CHEMBL4523704 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630740 (PROTEIN-PROTEIN INTERACTION), CHEMBL5251 (SINGLE PROTEIN), CHEMBL5291968 (PROTEIN-PROTEIN INTERACTION), CHEMBL5482987 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066563 (PROTEIN FAMILY), CHEMBL6066564 (PROTEIN FAMILY), CHEMBL6066565 (PROTEIN FAMILY), CHEMBL6193847 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

84 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 212,087 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3701238	FUTIBATINIB	4	813
CHEMBL3707348	ACALABRUTINIB	4	4,504
CHEMBL3786343	OLMUTINIB	4	1,776
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL4071161	TIRABRUTINIB	4	2,170
CHEMBL4085457	RITLECITINIB	4	708
CHEMBL4650485	PIRTOBRUTINIB	4	427
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL58	MITOXANTRONE	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL217092	SARACATINIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL3265032	ENTOSPLETINIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL3545154	POZIOTINIB	3
CHEMBL3545308	ROCILETINIB	3
CHEMBL3647420	PYROTINIB	3
CHEMBL3702854	RILZABRUTINIB	3

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 3 curated evidence items; also 1 oncogenic, 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
BTK C481S	Ibrutinib	Chronic Lymphocytic Leukemia	Resistance	CIViC B	EID1770 +1
BTK T316A	Ibrutinib	Chronic Lymphocytic Leukemia	Resistance	CIViC C	EID1985

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 (55 total), top 25:

Ligand	Action	Affinity	Parameter
BIIB091	Inhibition	10.15	pKd
luxeptinib	Inhibition	10.0	pIC50
branebrutinib	Inhibition	9.96	pIC50
BIIB129	Inhibition	9.52	pIC50
RN486	Inhibition	9.51	pKd
sofnobrutinib	Inhibition	9.41	pIC50
abivertinib	Inhibition	9.4	pIC50
spebrutinib	Inhibition	9.3	pIC50
BMS-986142	Inhibition	9.3	pIC50
compound 4g [PMID: 30893553]	Inhibition	9.28	pIC50
BTK inhibitor 16 [PMID: 30122225]	Inhibition	9.15	pIC50
vecabrutinib	Inhibition	9.14	pIC50
midobrutinib	Inhibition	9.09	pIC50
milrebrutinib	Inhibition	9.07	pIC50
birelentinib	Inhibition	9.07	pIC50
remibrutinib	Inhibition	9.0	pIC50
BIIB068	Inhibition	9.0	pIC50
ZYBT1	Irreversible inhibition	9.0	pIC50
compound 71 [WO2018191577A1]	Inhibition	9.0	pIC50
CNX-774	Inhibition	9.0	pIC50
ibrutinib	Inhibition	8.82	pIC50
rilzabrutinib	Inhibition	8.82	pIC50
CGI1746	Inhibition	8.72	pIC50
compound 9 [PMID: 26006010]	Inhibition	8.72	pIC50
compound 36 [PMID: 21958547]	Inhibition	8.71	pIC50

Binding affinities (BindingDB)

4160 measured of 6099 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(2-acryloyl-1,2,3,4- tetrahydroisoquinolin- 5-yl)-6-chloro-3-fluoro- 9H-carbazole-1- carboxamide	IC50	0.00026 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
4-(2-acryloyl-1,2,3,4- tetrahydroisoquinolin- 5-yl)-3-fluoro-9H- carbazole-1- carboxamide	IC50	0.0003 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
9-(2-acryloyl-1,2,3,4- tetrahydroisoquinolin- 5-yl)-8-fluoro-5H- pyrido[4,3-b]indole-6- carboxamide	IC50	0.0003 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
5-(2-acryloyl-1,2,3,4- tetrahydroisoquinolin- 5-yl)-6-chloro-2,3,4,9- tetrahydro-1H- carbazole-8- carboxamide	IC50	0.0006 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
4-(2-acryloyl-1,2,3,4- tetrahydroisoquinolin- 5-yl)-3-fluoro-7-(2- fluoroethyl)-9H- carbazole-1- carboxamide	IC50	0.029 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
5-fluoro-2,3-dimethyl-4-(1-prop-2-enoyl-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrol-5-yl)-1H-indole-7-carboxamide	IC50	0.04 nM	US-9688629: Indole carboxamide compounds
5-fluoro-2,3-dimethyl-4-(2-prop-2-enoyl-3,4-dihydro-1H-isoquinolin-8-yl)-1H-indole-7-carboxamide	IC50	0.04 nM	US-9688629: Indole carboxamide compounds
5-(2-Acryloyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-6-fluoro-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (Single Diastereomer)	IC50	0.045 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
4-[3-(ethenylsulfonylamino)phenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	IC50	0.046 nM	US-10266491: Carbazole derivatives
3-chloro-7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	IC50	0.047 nM	US-10266491: Carbazole derivatives
3-fluoro-4-(1-prop-2-enoyl-2,3-dihydroindol-6-yl)-9H-carbazole-1-carboxamide	IC50	0.049 nM	US-10266491: Carbazole derivatives
4-[(3S)-3-(3-cyclopropylprop-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide	IC50	0.05 nM	US-9802915: Indole carboxamide compounds
5-fluoro-2,3-dimethyl-4-(1-prop-2-enoylpiperidin-3-yl)-1H-indole-7-carboxamide	IC50	0.05 nM	US-9688629: Indole carboxamide compounds
1-(3-chloro-2,6-difluorophenyl)-3-(3-fluoro- 4-(7-(5-methyl-1H-imidazol-2-yl)-1- oxoisoindolin-4-yl)phenyl)urea	IC50	0.05 nM	US-9758508: 2,3-dihydro-isoindole-1-on derivative as BTK kinase suppressant, and pharmaceutical composition including same
3-fluoro-4-(1-prop-2-enoylpiperidin-3-yl)-9H-carbazole-1-carboxamide	IC50	0.05 nM	US-10266491: Carbazole derivatives
3-fluoro-4-(1-prop-2-enoyl-3,6-dihydro-2H-pyridin-5-yl)-7-(trifluoromethyl)-9H-carbazole-1-carboxamide	IC50	0.05 nM	US-10266491: Carbazole derivatives
4-[3-(ethenylsulfonylamino)phenyl]-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	IC50	0.051 nM	US-10266491: Carbazole derivatives
4-[(3S)-3-(3-cyclopropylprop-2-ynoylamino)piperidin-1-yl]-3-fluoro-9H-carbazole-1-carboxamide	IC50	0.052 nM	US-10266491: Carbazole derivatives
4-[3-[(1R,6R,8aR)-1-methyl-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	0.058 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
5-fluoro-2,3-dimethyl-4-[(3S)-3-(pent-2-ynoylamino)piperidin-1-yl]-1H-indole-7-carboxamide	IC50	0.06 nM	US-9802915: Indole carboxamide compounds
5-fluoro-4-[(3S)-3-(hex-2-ynoylamino)piperidin-1-yl]-2,3-dimethyl-1H-indole-7-carboxamide	IC50	0.06 nM	US-9802915: Indole carboxamide compounds
3-fluoro-7-(2-hydroxypropan-2-yl)-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-9H-carbazole-1-carboxamide	IC50	0.061 nM	US-10266491: Carbazole derivatives
4-(2-Acryloyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-3-fluoro-9H-carbazole-1-carboxamide (Single Enantiomeric Atropisomer)	IC50	0.067 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-3-fluoro-9H-carbazole-1-carboxamide	IC50	0.067 nM	US-10266491: Carbazole derivatives
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	IC50	0.069 nM	US-10266491: Carbazole derivatives
4-[3-[ethenylsulfonyl(methyl)amino]-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide	IC50	0.07 nM	US-9802915: Indole carboxamide compounds
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-2,3-dimethyl-1H-indole-7-carboxamide	IC50	0.07 nM	US-9688629: Indole carboxamide compounds
1-(2-chloro-3,6-difluorophenyl)-3-(3-fluoro- 4-(7-(5-methyl-1H-imidazol-2-yl)-1- oxoisoindolin-4-yl)phenyl)urea	IC50	0.07 nM	US-9758508: 2,3-dihydro-isoindole-1-on derivative as BTK kinase suppressant, and pharmaceutical composition including same
(6R,8aS)-6-(8-amino-1- {4-[(1R)-1-(3- cyclopropylphenyl)-1- hydroxyethyl]phenyl} imidazo[1,5-a]pyrazin-3- yl)hexahydroindolizin- 3(2H)-one	IC50	0.07 nM	US-10214546
(6R,8aS)-6-[8-amino-1-[4-[1-[3-(2,2-difluorocyclopropyl)phenyl]-1-hydroxyethyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]-2,5,6,7,8,8a-hexahydro-1H-indolizin-3-one	IC50	0.07 nM	US-10214546
Cis-4-(1-acryloylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-3-fluoro-9H-carbazole-1-carboxamide	IC50	0.07 nM	US-10266491: Carbazole derivatives
3-fluoro-4-(4-prop-2-enoyl-2,3-dihydro-1,4-benzothiazin-8-yl)-9H-carbazole-1-carboxamide	IC50	0.073 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
2-[3-[3-amino-7-(1-methylpyrazol-4-yl)-1H-indazol-5-yl]-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1-one	IC50	0.073 nM	US-10246457: Indazole and azaindazole Btk inhibitors
3-fluoro-4-[(3S)-3-(prop-2-enoylamino)piperidin-1-yl]-9H-carbazole-1-carboxamide	IC50	0.073 nM	US-10266491: Carbazole derivatives
4-[8-amino-3-[(4aS,7R)-1-oxo-4,4a,5,6,7,8-hexahydro-3H-pyrido[1,2-c][1,3]oxazin-7-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	0.075 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
3-fluoro-4-(4-prop-2-enoyl-2,3-dihydro-1,4-benzoxazin-8-yl)-9H-carbazole-1-carboxamide	IC50	0.075 nM	US-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
3-chloro-7-N,7-N-dimethyl-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1,7-dicarboxamide	IC50	0.075 nM	US-10266491: Carbazole derivatives
7-cyano-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-9H-carbazole-1-carboxamide	IC50	0.076 nM	US-10266491: Carbazole derivatives
3-chloro-7-(hydroxymethyl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	IC50	0.078 nM	US-10266491: Carbazole derivatives
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	IC50	0.079 nM	US-10266491: Carbazole derivatives
4-[3-(ethenylsulfonylamino)phenyl]-2,3-dimethyl-1H-indole-7-carboxamide	IC50	0.08 nM	US-9688629: Indole carboxamide compounds
5-fluoro-4-(4-fluoro-2-prop-2-enoyl-3,4-dihydro-1H-isoquinolin-5-yl)-2,3-dimethyl-1H-indole-7-carboxamide	IC50	0.08 nM	US-9688629: Indole carboxamide compounds
4-[3-[(2S,6R,8aS)-2-hydroxy-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	0.081 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
4-[8-amino-3-[(6R,8aS)-3-oxo-1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyridin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	0.083 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
4-[3-[(1S,6R,8aS)-1-methyl-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	0.085 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
7-(1,2-dihydroxyethyl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-9H-carbazole-1-carboxamide	IC50	0.088 nM	US-10266491: Carbazole derivatives
1-[3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2-yl)-2-(hydroxymethyl)phenyl]-3-[(5-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl)amino]pyrazole-4-carboxamide	IC50	0.09 nM	US-8729078: Inhibitors of bruton’s tyrosine kinase
1-[3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2-yl)-2-(hydroxymethyl)phenyl]-3-(4-methylsulfonylanilino)pyrazole-4-carboxamide	IC50	0.09 nM	US-8729078: Inhibitors of bruton’s tyrosine kinase
BDBM166759	IC50	0.09 nM	US-9802915: Indole carboxamide compounds
5-fluoro-2,3-dimethyl-4-(1-prop-2-enoyl-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b]pyridin-6-yl)-1H-indole-7-carboxamide	IC50	0.09 nM	US-9802915: Indole carboxamide compounds

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 41 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.85	IC50	0.014	nM	CHEMBL4762397
10.54	IC50	0.029	nM	CHEMBL5977366
10.40	IC50	0.04	nM	CHEMBL5826570
10.40	IC50	0.04	nM	CHEMBL5945342
10.35	IC50	0.045	nM	CHEMBL5884405
10.34	IC50	0.046	nM	CHEMBL5909954
10.33	IC50	0.047	nM	CHEMBL5789446
10.31	IC50	0.049	nM	CHEMBL5749648
10.30	IC50	0.05	nM	CHEMBL5741138
10.30	IC50	0.05	nM	CHEMBL5824452
10.30	IC50	0.05	nM	CHEMBL6004055
10.30	IC50	0.05	nM	CHEMBL5858594
10.30	IC50	0.05	nM	CHEMBL5799170
10.29	IC50	0.051	nM	CHEMBL5772754
10.28	IC50	0.052	nM	CHEMBL5824452
10.28	IC50	0.052	nM	CHEMBL5848923
10.24	IC50	0.058	nM	CHEMBL4113670
10.22	IC50	0.06	nM	CHEMBL5993286
10.22	IC50	0.06	nM	CHEMBL5836429
10.21	IC50	0.061	nM	CHEMBL5983201
10.17	IC50	0.068	nM	CHEMBL4237999
10.17	IC50	0.067	nM	CHEMBL5745824
10.17	IC50	0.067	nM	CHEMBL6042416
10.16	IC50	0.069	nM	CHEMBL5819531
10.15	IC50	0.07	nM	CHEMBL4648442
10.15	Kd	0.07	nM	BIIB-091
10.15	IC50	0.07	nM	CHEMBL4237999
10.15	IC50	0.07	nM	CHEMBL5820093
10.15	IC50	0.07	nM	CHEMBL4246324
10.15	IC50	0.07	nM	CHEMBL5995250
10.15	IC50	0.07	nM	CHEMBL5888728
10.15	IC50	0.07	nM	CHEMBL6042416
10.15	IC50	0.07	nM	CHEMBL5862023
10.15	IC50	0.07	nM	CHEMBL5757954
10.14	IC50	0.073	nM	CHEMBL5850088
10.14	IC50	0.073	nM	CHEMBL5962240
10.14	IC50	0.073	nM	CHEMBL5808322
10.12	IC50	0.075	nM	CHEMBL4113445
10.12	IC50	0.075	nM	CHEMBL5938181
10.12	IC50	0.076	nM	CHEMBL5958946
10.12	IC50	0.075	nM	CHEMBL6053298

PubChem BioAssay actives

2594 with measured affinity, of 6100 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
4-tert-butyl-N-[2-methyl-3-[5-[[methyl(prop-2-enoyl)amino]methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]phenyl]benzamide	1673837: Inhibition of full length human unphosphorylated BTK using FITC-Ahx-TSELKKVVALYDYMPMNAND-NH2 as substrate incubated for 60 mins in presence of ATP at Km concentration	ic50	<0.0001	uM
4-(4-phenoxyphenyl)-10-prop-2-enoyl-2,3,7,10-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),4,6-triene-5-carboxamide	1615344: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0001	uM
4-(4-phenoxyphenyl)-12-prop-2-enoyl-2,3,7,12-tetrazatricyclo[6.5.0.02,6]trideca-1(8),4,6-triene-5-carboxamide	1615344: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0001	uM
6-(4-phenoxyphenyl)-3-(1-prop-2-enoylpiperidin-4-yl)-5H-imidazo[1,2-b]pyrazole-7-carboxamide	1615344: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0001	uM
6-[(7S)-7-(prop-2-enoylamino)-5-azaspiro[2.4]heptan-5-yl]-2-[4-(2-pyrrolidin-1-ylethyl)anilino]pyridine-3-carboxamide	1418272: Inhibition of recombinant human full length N-terminal GST-tagged BTK (2 to 659 residues) expressed in baculovirus expression system using FITC-AHA-EEPLYWSFPAKKK-NH2 substrate measured after 90 mins by off-chip mobility shift assay	ic50	0.0001	uM
4-[6-(4-methoxybut-2-ynoylamino)quinolin-4-yl]oxy-N-pyridin-2-ylbenzamide	1720508: Inhibition of human recombinant full length N-terminal His6-tagged BTK expressed in baculovirus infected Sf9 cells using fluorescein labeled Blk/Lyntide substrate preincubated with enzyme for 60 mins followed by further incubation with substrate and ATP for 120 mins by IMAP assay	ic50	0.0001	uM
4-[3-(ethenylsulfonylamino)phenyl]-2,3-dimethyl-1H-indole-7-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0001	uM
4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide	1656238: Inhibition of recombinant human BTK using fluoresceinated peptide as substrate after 60 mins fluorescence assay	ic50	0.0001	uM
5-fluoro-2,3-dimethyl-4-[(3S)-3-(prop-2-ynoylamino)piperidin-1-yl]-1H-indole-7-carboxamide	1656238: Inhibition of recombinant human BTK using fluoresceinated peptide as substrate after 60 mins fluorescence assay	ic50	0.0001	uM
4-[3-[ethenylsulfonyl(methyl)amino]-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0001	uM
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-2,3-dimethyl-1H-indole-7-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0001	uM
2,3-dimethyl-4-[(3S)-3-(prop-2-ynoylamino)piperidin-1-yl]-1H-indole-7-carboxamide	1656238: Inhibition of recombinant human BTK using fluoresceinated peptide as substrate after 60 mins fluorescence assay	ic50	0.0001	uM
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0001	uM
4-[8-amino-1-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]cubane-1-carboxylic acid	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0001	uM
(1S,5R)-3-[8-amino-1-[4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]bicyclo[3.1.0]hexane-6-carboxylic acid	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0001	uM
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0001	uM
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820528: Binding affinity to wild-type human full length BTK (M1 to S659 residues) expressed in mammalian expression system by Kinomescan method	kd	0.0001	uM
cis-(1S,3R)-3-[8-amino-1-[4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]-1,3-dimethylcyclohexane-1-carboxylic acid	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0001	uM
2-[3-(2-amino-6-pyridin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one	1830219: Inhibition of human BTK-A using phosphorylated substrate in presence of ATP by microplate reader assay	ic50	0.0001	uM
2-[(6-methyl-3-pyridinyl)amino]-6-[(1R,4R)-5-prop-2-enoyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridine-3-carboxamide	1418272: Inhibition of recombinant human full length N-terminal GST-tagged BTK (2 to 659 residues) expressed in baculovirus expression system using FITC-AHA-EEPLYWSFPAKKK-NH2 substrate measured after 90 mins by off-chip mobility shift assay	ic50	0.0001	uM
4-[8-amino-3-[(3R,6S)-1-[(2S)-2-hydroxypropanoyl]-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711650: Reversible inhibition of recombinant full length BTK (unknown origin) baculovirus infected Sf9 cells using biotinylated EQEDEPEGDYFEWLE-NH2 peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 120 mins in presence of ATP by TR-FRET assay	ic50	0.0001	uM
(3S)-3-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]pyrrolidine-1-carboxamide	1820500: Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assay	ic50	0.0001	uM
10-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-[2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridinyl]amino]-6-oxo-3-pyridinyl]phenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one	1937987: Reversible inhibition of human BTK	ic50	0.0001	uM
Ibrutinib	1465438: Inhibition of human BTK using KVEKIGEGTYGVVYK as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition by filter binding method	ic50	0.0001	uM
11-[(E)-4-(dimethylamino)but-2-enoyl]-4-(4-phenoxyphenyl)-2,3,7,11-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),4,6-triene-5-carboxamide	1615344: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0002	uM
4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	1678386: Inhibition of recombinant full-length His-tagged human BTK expressed in baculovirus expression system using fluoresceinated peptide as substrate incubated for 60 mins by fluorescence assay	ic50	0.0002	uM
N-[3-[6-amino-5-[2-[methyl(prop-2-enoyl)amino]ethoxy]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]-4-cyclopropyl-2-fluorobenzamide	1878117: Binding affinity to BTK (unknown origin) assessed as dissociation constant by KINOMEscan analysis	kd	0.0002	uM
3-tert-butyl-N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]pyrrolidine-1-carboxamide	1696245: Inhibition of recombinant human full-length N-terminal His6-tagged BTK expressed in baculovirus infected Sf21 insect cells using fluorescein-labeled polyGAT peptide substrate measured after 30 mins by TR-FRET assay	ic50	0.0002	uM
2,3-dimethyl-4-[3-(prop-2-enoylamino)phenyl]-1H-indole-7-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
2,3-dimethyl-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-1H-indole-7-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
4-[8-amino-1-[4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]bicyclo[2.2.2]octane-1-carboxylic acid	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0002	uM
cis-(1S,3R)-3-[8-amino-1-[4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]-1,3-dimethylcyclopentane-1-carboxylic acid	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0002	uM
4-[8-amino-1-[4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]bicyclo[2.2.1]heptane-1-carboxylic acid	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0002	uM
2-[3-[6-amino-2-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one	1368714: Inhibition of His-tagged lambda phosphatase pre-treated N-terminal DYKDDDDK tagged and biotinylated BTK unactivated form (unknown origin) using FITC-labeled Srctide substrate and ATP by microfluidic mobility shift assay	ic50	0.0002	uM
2-[3-[6-amino-2-[(1-propan-2-ylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one	1368714: Inhibition of His-tagged lambda phosphatase pre-treated N-terminal DYKDDDDK tagged and biotinylated BTK unactivated form (unknown origin) using FITC-labeled Srctide substrate and ATP by microfluidic mobility shift assay	ic50	0.0002	uM
7-(2-hydroxypropan-2-yl)-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-9H-carbazole-1-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
7-(2-hydroxypropan-2-yl)-4-[3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
7-(2-hydroxypropan-2-yl)-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1399226: Inhibition of recombinant human full-length His-tagged BTK cytoplasmic domain expressed in baculovirus expression system using fluorescence-labelled peptide as substrate measured after 60 mins by fluorescence assay	ic50	0.0002	uM
1-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]triazole-4-carboxamide	1820500: Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assay	ic50	0.0002	uM
2-(4-phenoxyphenyl)-7-[(prop-2-enoylamino)methyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1615344: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay	ic50	0.0002	uM
oxolan-2-ylmethyl 2-[4-[[5-chloro-4-[3-(prop-2-enoylamino)anilino]pyrimidin-2-yl]amino]phenoxy]acetate	1426139: Inhibition of N-terminal His-tagged full length human recombinant BTK expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) peptide substrate incubated for 60 mins by ADP-Glo luminescence assay	ic50	0.0002	uM
4-[8-amino-3-[(1R,3S)-3-carbamoylcyclohexyl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1432830: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay	ic50	0.0002	uM
3-tert-butyl-N-[(1S)-6-[2-(1-propan-2-ylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]-1,2,3,4-tetrahydronaphthalen-1-yl]-1,2,4-oxadiazole-5-carboxamide	1763450: Inhibition of BTK (unknown origin)	ic50	0.0002	uM
1-[(3R)-3-[3-(4-phenoxyphenyl)indazol-1-yl]piperidin-1-yl]prop-2-en-1-one	1576940: Covalent inhibition of N-terminal GST-fused human BTK (2-659(end) amino acids) expressed in baculovirus expression system using FITC-AHA-EEPLYWSFPAKKK-NH2 as substrate incubated for 90 mins by microfluidic off-Chip Mobility Shift Assay	ic50	0.0002	uM
4-[8-amino-3-[(3R,6S)-6-methyl-1-(oxolane-2-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711650: Reversible inhibition of recombinant full length BTK (unknown origin) baculovirus infected Sf9 cells using biotinylated EQEDEPEGDYFEWLE-NH2 peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 120 mins in presence of ATP by TR-FRET assay	ic50	0.0002	uM
4-[3-[(3R,6S)-1-acetyl-6-methylpiperidin-3-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711650: Reversible inhibition of recombinant full length BTK (unknown origin) baculovirus infected Sf9 cells using biotinylated EQEDEPEGDYFEWLE-NH2 peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 120 mins in presence of ATP by TR-FRET assay	ic50	0.0002	uM
4-[8-amino-3-[(3R,6S)-1-[(2R)-2-hydroxypropanoyl]-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711650: Reversible inhibition of recombinant full length BTK (unknown origin) baculovirus infected Sf9 cells using biotinylated EQEDEPEGDYFEWLE-NH2 peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 120 mins in presence of ATP by TR-FRET assay	ic50	0.0002	uM
N-[2-[4-amino-6-[3-methyl-4-[[4-(2-methylpropyl)-2-oxopiperazin-1-yl]methyl]phenyl]pyrimidin-5-yl]oxyethyl]-N-methylprop-2-enamide	1878101: Inhibition of BTK (unknown origin)	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
rilzabrutinib	affects binding, decreases activity, decreases phosphorylation	6
ibrutinib	decreases expression, decreases phosphorylation, increases reaction, decreases activity, decreases response to substance (+1 more)	6
(+)-JQ1 compound	decreases expression, decreases phosphorylation, increases reaction, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases mutagenesis	3
Dasatinib	affects binding, decreases activity, decreases phosphorylation	2
Resveratrol	affects cotreatment, increases expression, affects binding, decreases reaction, increases reaction (+1 more)	2
fenebrutinib	decreases activity	1
evobrutinib	affects binding, decreases activity	1
remibrutinib	affects binding, decreases activity	1
orelabrutinib	affects binding, decreases activity	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pyrachlostrobin	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
GSK1210151A	decreases expression, decreases phosphorylation	1
methylsulfonyl benzothiazole	affects binding	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

1836 unique, capped per target: 1810 binding, 23 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4349424	Binding	Protac activity at E3 ubiquitin ligase/BTK in human NAMALWA cells assessed as BTK degradation	Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation. — Eur J Med Chem
CHEMBL1963733	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: BTK	PubChem BioAssay data set
CHEMBL4407571	ADMET	Inhibition of full-length recombinant human His-tagged BTK cytoplasmic domain expressed in baculovirus expression system at 25 uM using FRET-labeled tyr 01 peptide as substrate measured after 1 hr by Z’-lyte assay relative to control	Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase. — J Med Chem

Cellosaurus cell lines

21 cell lines: 16 cancer cell line, 3 transformed cell line, 1 induced pluripotent stem cell, 1 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2Z01	ID00001	Transformed cell line	Male
CVCL_2Z21	ID00035	Transformed cell line	Male
CVCL_A4XG	SDQLCHi039-A	Induced pluripotent stem cell	Male
CVCL_B7WB	Abcam Raji BTK KO	Cancer cell line	Male
CVCL_B9WU	Abcam THP-1 BTK KO	Cancer cell line	Male
CVCL_C3ES	NK-NJ	Cancer cell line	Male
CVCL_C6YV	Abcam PC-3 BTK KO	Cancer cell line	Male
CVCL_E1E7	Ubigene U-2932 BTK KO	Cancer cell line	Female
CVCL_E8IZ	TMD8-BTK-A428D-KI-1B4	Cancer cell line	Male
CVCL_E8J0	TMD8-BTK-C481F-KI	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00074984	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) as Compared to Placebo in Patients With Advanced Fabry Disease
NCT00081497	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
NCT00097890	PHASE4	COMPLETED	Replagal Enzyme Replacement Therapy for Adults With Fabry Disease
NCT00140621	PHASE4	COMPLETED	A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease
NCT00230607	PHASE4	TERMINATED	Study of the Effects of Fabrazyme Treatment on Lactation and Infants
NCT00312767	PHASE4	WITHDRAWN	A Study in Patients With Fabry Disease Who Are on Chronic Hemodialysis Therapy for Treatment of End-stage Renal Insufficiency.
NCT00487630	PHASE4	UNKNOWN	Evaluation of Efficacy and Safety of Agalsidase Beta in Heterozygous Females for Fabry Disease
NCT01650779	PHASE4	COMPLETED	A Study Evaluating Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta
NCT01997489	PHASE4	COMPLETED	Ophthalmic Findings During 10-year Enzyme Substitution of Danish Fabry Patients.
NCT04143958	PHASE4	WITHDRAWN	To Assess the Glycosphingolipid Clearance and Clinical Effects of Switching to Agalsidase Beta (Fabrazyme) Versus Continuing on Agalsidase Alfa (Replagal) in Male Patients With Classic Fabry Disease
NCT05054387	PHASE4	COMPLETED	China Post-marketing Surveillance (PMS) Study of Fabrazyme®
NCT05067868	PHASE4	RECRUITING	A Study of Replagal in Children and Adults With Fabry Disease in India
NCT06019728	PHASE4	COMPLETED	A Prospective Study to Investigate Safety and Tolerability of Shorter Infusion of Fabrazyme
NCT00466258	PHASE4	COMPLETED	LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)
NCT01949818	PHASE4	UNKNOWN	Treatment of Diffuse Large B Cell Lymphoma
NCT02752815	PHASE4	UNKNOWN	Reduced Chemotherapy in Low Risk DLBCL
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03513601	PHASE4	UNKNOWN	Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma
NCT03579082	PHASE4	UNKNOWN	A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma
NCT05108805	PHASE4	COMPLETED	Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting
NCT05518383	PHASE4	RECRUITING	B-cell Mature Non-Hodgkin’s Lymphoma Treatment Protocol in Children and Adolescents 2021
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT00074971	PHASE3	COMPLETED	A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
NCT00701415	PHASE3	COMPLETED	A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
NCT00864851	PHASE3	COMPLETED	Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease
NCT00925301	PHASE3	COMPLETED	Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
NCT01124643	PHASE3	COMPLETED	Extension Study of TKT028 Evaluating Safety and Clinical Outcomes of Replagal® in Adult Patients With Fabry Disease
NCT01218659	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease
NCT01298141	PHASE3	COMPLETED	A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease