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BTK

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Also known as ATKXLAPSCTK1

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): 1,009 total — 254 pathogenic, 115 likely-pathogenic (top 3% of genes corpus-wide)
  • Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈5% of expected missense variation)
  • GTEx eGene: eQTL in 41 tissues, sQTL in 0 (q < 0.05)
  • Phenotypes (HPO): 77
  • Drug target: yes — 19 curated mechanism-of-action drugs, 1 via a complex or family; 84 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
  • Approved drugs (ChEMBL mechanism of action): 5 — Acalabrutinib, Ibrutinib, Pirtobrutinib, +2 more
  • Approved drugs acting on a complex or family including it: 1 — Ritlecitinib (TEC family kinase)
  • Precision-oncology evidence (CIViC): 2 curated variant–drug associations
  • Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
  • Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
  • MANE Select transcript: NM_000061
  • Interaction hub: 3,142 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1133
Approved symbolBTK
NameBruton tyrosine kinase
LocationXq22.1
Locus typegene with protein product
StatusApproved
AliasesATK, XLA, PSCTK1
Ensembl geneENSG00000010671
Ensembl biotypeprotein_coding
OMIM300300
Entrez695

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 21 protein_coding, 9 nonsense_mediated_decay, 7 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000308731

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 4

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, ENST00001033630, ENST00001132204

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

CCDS: CCDS14482, CCDS76002, CCDS76003

Canonical transcript exons

ENST00000308731 — 19 exons

ExonStartEnd
ENSE00000673977101354630101354694
ENSE00000673980101356052101356268
ENSE00000673981101356784101356955
ENSE00000673983101358310101358437
ENSE00000673984101358617101358696
ENSE00001601394101362173101362240
ENSE00001608013101360568101360755
ENSE00001643950101374536101374634
ENSE00001643964101362561101362689
ENSE00001646803101371633101371701
ENSE00001698702101369998101370079
ENSE00001702496101353194101353351
ENSE00001712685101360088101360150
ENSE00001780523101353870101353988
ENSE00001801955101359293101359347
ENSE00003624587101357509101357583
ENSE00003964492101386062101386191
ENSE00003964497101349450101349956
ENSE00003964522101375144101375314

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.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, spleen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BTK is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 41 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Testiseqtl6.2e-35-0.56X:101390479:T:C
Nerve Tibialeqtl3.5e-34-0.24X:101354559:G:A
Adipose Subcutaneouseqtl8.9e-19-0.13X:101354559:G:A
Lungeqtl7.1e-18-0.21X:101354559:G:A
Whole Bloodeqtl3.3e-17-0.11X:101354559:G:A
Skin Sun Exposed Lower legeqtl2.9e-11-0.16X:101354559:G:A
Adipose Visceral Omentumeqtl4.1e-11-0.14X:101354559:G:A
Cells EBV-transformed lymphocyteseqtl4.3e-11-0.19X:101354559:G:A
Brain Hippocampuseqtl5.4e-11-0.18X:101354559:G:A
Adrenal Glandeqtl2.3e-10-0.19X:101354559:G:A
Brain Hypothalamuseqtl2.5e-10-0.18X:101354559:G:A
Brain Spinal cord cervical c-1eqtl6.7e-10-0.17X:101354559:G:A
Heart Atrial Appendageeqtl1.1e-09-0.17X:101354559:G:A
Breast Mammary Tissueeqtl1.1e-08-0.13X:101354559:G:A
Esophagus Gastroesophageal Junctioneqtl2.4e-08-0.15X:101354559:G:A
Skin Not Sun Exposed Suprapubiceqtl2.6e-08-0.15X:101354559:G:A
Spleeneqtl4.0e-08-0.19X:101354559:G:A
Muscle Skeletaleqtl3.8e-07-0.15X:101354559:G:A
Thyroideqtl4.6e-07-0.12X:101354559:G:A
Esophagus Musculariseqtl8.6e-07-0.12X:101354559:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter IDTPM avgSamples expressed
19995114.8837565
1999490.081740
1999480.033112

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
monocyteCL:000057698.10gold quality
mononuclear cellCL:000084297.81gold quality
leukocyteCL:000073897.70gold quality
granulocyteCL:000009497.46gold quality
spleenUBERON:000210694.99gold quality
bone marrow cellCL:000209294.27gold quality
lymph nodeUBERON:000002993.86gold quality
bloodUBERON:000017893.63gold quality
vermiform appendixUBERON:000115493.36gold quality
epithelium of nasopharynxUBERON:000195192.24gold quality
nasopharynxUBERON:000172892.22gold quality
bone marrowUBERON:000237191.17gold quality
type B pancreatic cellCL:000016989.64gold quality
caecumUBERON:000115389.62gold quality
right lungUBERON:000216789.61gold quality
olfactory bulbUBERON:000226489.33gold quality
upper lobe of left lungUBERON:000895287.93gold quality
upper lobe of lungUBERON:000894887.00gold quality
rectumUBERON:000105286.97gold quality
small intestine Peyer’s patchUBERON:000345485.46gold quality
gall bladderUBERON:000211085.29gold quality
smooth muscle tissueUBERON:000113584.28gold quality
colonic epitheliumUBERON:000039784.21gold quality
trabecular bone tissueUBERON:000248383.77gold quality
superficial temporal arteryUBERON:000161483.33gold quality
C1 segment of cervical spinal cordUBERON:000646983.25gold quality
small intestineUBERON:000210883.02gold quality
right coronary arteryUBERON:000162582.77gold quality
spinal cordUBERON:000224081.51gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047381.45gold quality
subcutaneous adipose tissueUBERON:000219081.39gold quality
lungUBERON:000204881.10gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099181.09gold quality
hair follicleUBERON:000207380.93gold quality
tonsilUBERON:000237280.84gold quality
left ventricle myocardiumUBERON:000656680.36gold quality
amniotic fluidUBERON:000017379.95gold quality
omental fat padUBERON:001041479.94gold quality
peritoneumUBERON:000235879.91gold quality
cardiac muscle of right atriumUBERON:000337979.65gold quality
male germ cellCL:000001579.50gold quality
adipose tissue of abdominal regionUBERON:000780879.35gold quality
visceral pleuraUBERON:000240179.26gold quality
adipose tissueUBERON:000101378.47gold quality
mucosa of transverse colonUBERON:000499178.45gold quality
spermCL:000001978.35gold quality
tibial nerveUBERON:000132378.10gold quality
connective tissueUBERON:000238477.93gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450277.64gold quality
mucosa of stomachUBERON:000119977.60gold quality
pleuraUBERON:000097777.44gold quality
intestineUBERON:000016077.35gold quality
transverse colonUBERON:000115777.31gold quality
esophagogastric junction muscularis propriaUBERON:003584176.78gold quality
parietal pleuraUBERON:000240076.68gold quality
lower esophagus muscularis layerUBERON:003583376.65gold quality
lower esophagusUBERON:001347376.63gold quality
coronary arteryUBERON:000162176.51gold quality
left coronary arteryUBERON:000162676.47gold quality
right adrenal gland cortexUBERON:003582776.41gold quality
skin of legUBERON:000151176.19gold quality
germinal epithelium of ovaryUBERON:000130475.98silver quality
minor salivary glandUBERON:000183075.97gold quality
colonUBERON:000115575.87gold quality
descending thoracic aortaUBERON:000234575.85gold quality
duodenumUBERON:000211475.84gold quality
large intestineUBERON:000005975.82gold quality
right adrenal glandUBERON:000123375.62gold quality
left adrenal gland cortexUBERON:003582575.62gold quality
lower lobe of lungUBERON:000894975.58silver quality
adrenal cortexUBERON:000123575.24gold quality
left adrenal glandUBERON:000123474.98gold quality
layer of synovial tissueUBERON:000761674.89silver quality
body of stomachUBERON:000116174.81gold quality
skin of abdomenUBERON:000141674.76gold quality
zone of skinUBERON:000001474.69gold quality
substantia nigraUBERON:000203874.61gold quality
cervix epitheliumUBERON:000480174.56gold quality
muscle layer of sigmoid colonUBERON:003580574.56gold quality
thoracic aortaUBERON:000151574.51gold quality
mouth mucosaUBERON:000372974.43gold quality
saliva-secreting glandUBERON:000104474.33gold quality
ascending aortaUBERON:000149674.32gold quality
fundus of stomachUBERON:000116074.06gold quality
sigmoid colonUBERON:000115974.05gold quality
esophagusUBERON:000104374.04gold quality
midbrainUBERON:000189174.02gold quality
mammary ductUBERON:000176573.73silver quality
thymusUBERON:000237073.64silver quality
stomachUBERON:000094573.40gold quality
urinary bladderUBERON:000125573.36gold quality
palpebral conjunctivaUBERON:000181273.15gold quality
epithelial cell of pancreasCL:000008373.14gold quality
adrenal glandUBERON:000236973.13gold quality
left uterine tubeUBERON:000130373.07gold quality
myocardiumUBERON:000234972.85gold quality
anatomical systemUBERON:000046772.81gold quality
material anatomical entityUBERON:000046572.80gold quality
multicellular organismUBERON:000046872.80gold quality
placentaUBERON:000198772.42gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-MTAB-9067yes12.38
E-MTAB-6701yes11.43
E-ANND-3yes11.34
E-CURD-112yes11.23
E-CURD-122yes8.83
E-HCAD-10yes6.97
E-MTAB-9801yes5.49
E-MTAB-7381no393.65
E-MTAB-7303no82.64
E-MTAB-6678no3.98
E-MTAB-5061no3.79

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Tonsiltissue62.7high
Lymph nodetissue41.8high
Spleentissue29.2high
Bone marrowtissue24.2medium
Appendixtissue23.4high
Lungtissue15.9medium
Hypothalamustissue8.3
Spinal cordtissue8.3
Periaqueductal graytissue7.7
Thymustissue7.6
Urinary bladdertissue7.5not detected
Substantia nigratissue7.1
Rectumtissue6.8low
Corpus callosumtissue6.5
Ponstissue6.4
Medulla oblongatatissue6.4
Septumtissue6.2
Gallbladdertissue5.9not detected
Midbraintissue5.8
Smooth muscletissue5.6not detected
Stomach 1tissue5.4not detected
Placentatissue5.4high
Colontissue5.1low
Adipose tissuetissue4.9not detected
Thalamustissue4.7
Putamentissue4.4
Livertissue4.4not detected
Small intestinetissue4.4not detected
Ventral forebraintissue4.0
Superior colliculitissue3.9
Amygdalatissue3.7
Hippocampal formationtissue3.6
Cervixtissue3.4not detected
Basal gangliatissue3.3not detected
Breasttissue3.0not detected
Esophagustissue2.9not detected
Duodenumtissue2.5not detected
Cerebral cortextissue2.4not detected
Motor cortextissue2.4
Entorhinal cortextissue2.3
Olfactory bulbtissue2.3
Retrosplenial cortextissue2.3
Temporal cortextissue2.2
Prefrontal cortextissue2.1
Insular cortextissue2.1
Salivary glandtissue2.0not detected
Endometrium 1tissue1.9not detected
Occipital cortextissue1.9
Seminal vesicletissue1.8not detected
Adrenal glandtissue1.8not detected
Retrosplenial and cingulate cortextissue1.8
Somatosensory cortextissue1.8
Choroid plexustissue1.7
Fallopian tubetissue1.6not detected
Vaginatissue1.5not detected
Tonguetissue1.4
Frontal cortextissue1.3
Locus coeruleustissue1.3
Prostatetissue1.3not detected
Heart muscletissue1.2not detected

Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Ventral spinal cord (8.3), Dorsal spinal cord (7.7), Lateral funiculus (white matter) (7.4), White matter (6.5), Medial olivary nucleus (4.6).

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)

Targeting BTK by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 32 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4481100.0066.421669
HSA-MIR-4745-5P99.9865.951028
HSA-MIR-590-3P99.9674.346478
HSA-MIR-498-5P99.7669.641807
HSA-MIR-6764-5P99.7567.892304
HSA-MIR-3059-5P99.7069.932491
HSA-MIR-6715B-5P99.6469.631420
HSA-MIR-451699.6167.783390
HSA-MIR-1915-3P99.5866.791988
HSA-MIR-426999.5569.891373
HSA-MIR-360999.5269.892587
HSA-MIR-548AH-5P99.5269.732626
HSA-MIR-5571-5P99.4966.991764
HSA-MIR-425199.4069.193363
HSA-MIR-888-5P99.3070.151855
HSA-MIR-3160-5P99.2869.071938
HSA-MIR-4667-3P99.2665.451608
HSA-MIR-4685-5P99.2565.991563
HSA-MIR-6837-5P99.2565.471632
HSA-MIR-443499.1067.011984
HSA-MIR-570399.1067.092053
HSA-MIR-628-3P99.0468.37814
HSA-MIR-62298.9966.481050
HSA-MIR-426098.7865.37848
HSA-MIR-5197-3P98.7167.051905
HSA-MIR-6780A-3P98.4267.491518
HSA-MIR-7113-5P97.8867.331735
HSA-MIR-7847-3P96.6364.58952
HSA-MIR-24-1-5P95.5765.85492
HSA-MIR-24-2-5P95.5766.16484

Functional genomics

Regional missense constraint (gnomAD)

ENST00000308731 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)Missense obs / expo/eConstrained
X:101,349,888–101,357,55579 / 217.70.36no
X:101,357,556–101,358,3860 / 25.20.00yes (p 5.2e-07)
X:101,358,387–101,375,284115 / 258.30.45no
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

OrganismSymbolGene ID
danio_reriobtkENSDARG00000004433
mus_musculusBtkENSMUSG00000031264
rattus_norvegicusBtkENSRNOG00000052407

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88216) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 46 distinct phenotype terms.

Mouse phenotype (MP)Records
decreased IgM level4
decreased B cell proliferation4
decreased mature B cell number4
decreased IgG3 level4
decreased B cell number3
abnormal B cell differentiation2
abnormal bone marrow cell number1
decreased neutrophil cell number1
spleen hypoplasia1
decreased body weight1
impaired myelopoiesis1
abnormal immune system physiology1
abnormal humoral immune response1
autoimmune response1
abnormal lymphopoiesis1
abnormal pre-B cell morphology1
abnormal macrophage physiology1
abnormal B cell physiology1
decreased immunoglobulin level1
abnormal neutrophil physiology1
impaired neutrophil phagocytosis1
decreased IgD level1
increased IgG level1
increased IgM level1
increased IgE level1

+21 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Gallus gallusP00523100.0%Diamond
Drosophila melanogasterQ08012100.0%Diamond
Drosophila simulansQ6YKA8100.0%Diamond
Bos taurusA0JNB099.6%Diamond
Sus scrofaA1Y2K199.4%Diamond
Pongo abeliiQ5R68599.4%Diamond
Felis catusP1423898.7%Diamond
Calliphora vicinaP1168198.6%Diamond
Aotus nancymaaeQ5PXS198.4%Diamond
Xenopus laevisP1311597.9%Diamond
Macaca fascicularisQ95M3097.8%Diamond
Xenopus tropicalisQ6GUF497.6%Diamond
Saimiri sciureusQ95KR796.9%Diamond
Canis lupus familiarisA0A8I3NFE295.9%Diamond
Xiphophorus helleriiP2744694.4%Diamond
Avian sarcoma virus PR2257P15054100.0%Diamond
Avian sarcoma virus S2P1408599.8%Diamond
Avian sarcoma virus S1P1408499.6%Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)P1044799.3%Diamond
Gardner-Arnstein feline sarcoma virusP0054299.1%Diamond
Snyder-Theilen feline sarcoma virusP0054399.1%Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)P0052499.0%Diamond
Avian sarcoma virus RASV1441P0052599.0%Diamond
Rous sarcoma virus - Prague CP0052699.0%Diamond
Rous sarcoma virus (strain H-19)P2502099.0%Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)P6318599.0%Diamond
Y73 sarcoma virusP0052798.9%Diamond
Abelson murine leukemia virusP0052198.7%Diamond
Rous sarcoma virus (strain PA101T)P3169395.6%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
TIMM8Aprotein-coding1678
ARMCX4protein-coding100131755
GLAprotein-coding2717
HNRNPH2protein-coding3188
RPL36Aprotein-coding6173
RPL36A-HNRNPH2protein-coding100529097

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. Interacts with STAC2; this interaction affects association with PLCG2 and subsequent PLCG2 phosphorylation.

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 IDNamesCanonical?
Q06187-1BTK-Ayes
Q06187-2BTK-C

RefSeq proteins (3): NP_000052, NP_001274273, NP_001274274 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR000980SH2Domain
IPR001245Ser-Thr/Tyr_kinase_cat_domDomain
IPR001452SH3_domainDomain
IPR001562Znf_Btk_motifConserved_site
IPR001849PH_domainDomain
IPR008266Tyr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR011993PH-like_dom_sfHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR020635Tyr_kinase_cat_domDomain
IPR035574BTK_SH3Domain
IPR036028SH3-like_dom_sfHomologous_superfamily
IPR036860SH2_dom_sfHomologous_superfamily
IPR050198Non-receptor_tyrosine_kinasesFamily

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.

SubstrateKm (mM)Measurements
ATP0.014–17.6412
[KDSRC KINASE]-L-TYROSINE0.0057–0.2412
POLY(GLU4-TYR)0.018–0.65910
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO0.0571
S1 PEPTIDE0.0371
EEEEY—0

Catalyzed reactions (Rhea)

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

UniProt features (240 total): sequence variant 117, strand 37, helix 27, modified residue 15, binding site 13, turn 10, 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)

showing 30 of 170 structures by resolution:

PDBTitleMethodResolution (Å)
5P9JBTK1 COCRYSTALLIZED WITH IBRUTINIBX-RAY DIFFRACTION1.08
6DI1CRYSTAL STRUCTURE OF BTK IN COMPLEX WITH COVALENT FRAGMENT LIGANDX-RAY DIFFRACTION1.1
5P9IBTK1 SOAKED WITH IBRUTINIB-RevX-RAY DIFFRACTION1.11
6HRPCRYSTAL STRUCTURE OF BTK KINASE DOMAIN COMPLEXED WITH …X-RAY DIFFRACTION1.12
6E4FCrystal structure of ARQ 531 in complex with the kinase domain of BTKX-RAY DIFFRACTION1.15
4RFZCrystal structure of BTK kinase domain complexed with …X-RAY DIFFRACTION1.17
7L5OCrystal structure of the noncovalently bonded complex of rilzabrutinib with BTKX-RAY DIFFRACTION1.21
5P9LBTK1 IN COMPLEX WITH CC 292X-RAY DIFFRACTION1.25
6DI9CRYSTAL STRUCTURE OF BTK IN COMPLEX WITH COVALENT INHIBITORX-RAY DIFFRACTION1.25
6J6MCo-crystal structure of BTK kinase domain with ZanubrutinibX-RAY DIFFRACTION1.25
7N5OFragment-Based Discovery of a Novel Bruton’s Tyrosine Kinase InhibitorX-RAY DIFFRACTION1.25
5P9KCRYSTAL STRUCTURE OF BTK with CNX 774X-RAY DIFFRACTION1.28
6BLNBTK complex with compound 13X-RAY DIFFRACTION1.3
6DI0CRYSTAL STRUCTURE OF BTK IN COMPLEX WITH FRAGMENT LIGANDX-RAY DIFFRACTION1.3
8FLVBruton’s tyrosine kinase in complex with compound 34X-RAY DIFFRACTION1.3
5U9DDiscovery of a potent BTK inhibitor with a novel binding mode using parallel selections …X-RAY DIFFRACTION1.33
7KXMBTK1 SOAKED WITH COMPOUND 5, Y551 IS SEQUESTEREDX-RAY DIFFRACTION1.33
8FLNCrystal structure of BTK C481S kinase domain in complex with pirtobrutinibX-RAY DIFFRACTION1.33
6X3PCo-structure of BTK kinase domain with L-005298385 inhibitorX-RAY DIFFRACTION1.34
7KXNBTK1 SOAKED WITH COMPOUND 26X-RAY DIFFRACTION1.34
4RX5Bruton’s tyrosine kinase (BTK) with pyridazinone compound 23X-RAY DIFFRACTION1.36
6HRTCRYSTAL STRUCTURE OF BTK KINASE DOMAIN COMPLEXED WITH …X-RAY DIFFRACTION1.36
6TT2The PH domain of Bruton’s tyrosine kinase mutant R28CX-RAY DIFFRACTION1.36
7KXQBTK1 SOAKED WITH COMPOUND 30X-RAY DIFFRACTION1.38
5KUPBruton’s tyrosine kinase (BTK) with pyridazinone compound 9X-RAY DIFFRACTION1.39
6NFHBTK in complex with inhibitor …X-RAY DIFFRACTION1.4
6VXQBruton’s tyrosine kinase in complex with compound 5X-RAY DIFFRACTION1.4
7YC9Co-crystal structure of BTK kinase domain with inhibitorX-RAY DIFFRACTION1.4
9Y57Co-crystal structure of BTK kinase domain with non-covalent inhibitorX-RAY DIFFRACTION1.4
5P9MBTK1 BINDS COVALENTLY TO HY-15771 ONO-4059X-RAY DIFFRACTION1.41

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q06187-F184.950.52

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

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)

PositionRole
521proton acceptor

Ligand- & substrate-binding residues (13)

PositionRole
261D-myo-inositol 1,3,4,5-tetrakisphosphate
281D-myo-inositol 1,3,4,5-tetrakisphosphate
391D-myo-inositol 1,3,4,5-tetrakisphosphate
531D-myo-inositol 1,3,4,5-tetrakisphosphate
143Zn(2+)
154Zn(2+)
155Zn(2+)
165Zn(2+)
408–416ATP
430ATP
474–477clofedanol
474–477dasatinib
542clofedanol

Post-translational modifications (15)

TypePositions
N-acetylalanine2
Phosphoserine21, 55, 115, 180, 604, 623, 659
Phosphotyrosine40, 223, 344, 361, 551, 617
Phosphothreonine191

Mutagenesis-validated functional residues (8)

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

Function

Pathways and Gene Ontology

Reactome pathways

12 curated (TAS) of 45; 14 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

45 pathways:

IDPathwayEvidence
R-HSA-9664422FCGR3A-mediated phagocytosis ⚕curated
R-HSA-5603041IRAK4 deficiency (TLR2/4) ⚕curated
R-HSA-5602498MyD88 deficiency (TLR2/4) ⚕curated
R-HSA-9679191Potential therapeutics for SARS ⚕curated
R-HSA-2424491DAP12 signalingcurated
R-HSA-1236974ER-Phagosome pathwaycurated
R-HSA-416482G alpha (12/13) signalling eventscurated
R-HSA-416476G alpha (q) signalling eventscurated
R-HSA-8964315G beta:gamma signalling through BTKcurated
R-HSA-166058MyD88:MAL(TIRAP) cascade initiated on plasma membranecurated
R-HSA-5663213RHO GTPases Activate WASPs and WAVEscurated
R-HSA-2029482Regulation of actin dynamics for phagocytic cup formationcurated
R-HSA-1643685Disease ⚕—
R-HSA-5602358Diseases associated with the TLR signaling cascade ⚕—
R-HSA-5260271Diseases of Immune System ⚕—
R-HSA-5663205Infectious disease ⚕—
R-HSA-9658195Leishmania infection ⚕—
R-HSA-9664417Leishmania phagocytosis ⚕—
R-HSA-9664407Parasite infection ⚕—
R-HSA-9824443Parasitic Infection Pathways ⚕—
R-HSA-9679506SARS-CoV Infections ⚕—
R-HSA-9824446Viral Infection Pathways ⚕—
R-HSA-1280218Adaptive Immune System—
R-HSA-983695Antigen activates B Cell Receptor (BCR) leading to generation of second messengerselectronic
R-HSA-1236975Antigen processing-Cross presentation—
R-HSA-983169Class I MHC mediated antigen processing & presentation—
R-HSA-2172127DAP12 interactions—
R-HSA-2871809FCERI mediated Ca+2 mobilizationelectronic
R-HSA-2454202Fc epsilon receptor (FCERI) signaling—
R-HSA-2029480Fcgamma receptor (FCGR) dependent phagocytosis—
R-HSA-397795G-protein beta:gamma signalling—
R-HSA-388396GPCR downstream signalling—
R-HSA-168256Immune System—
R-HSA-168249Innate Immune System—
R-HSA-195258RHO GTPase Effectors—
R-HSA-162582Signal Transduction—
R-HSA-372790Signaling by GPCR—
R-HSA-194315Signaling by Rho GTPases—
R-HSA-9716542Signaling by Rho GTPases, Miro GTPases and RHOBTB3—
R-HSA-983705Signaling by the B Cell Receptor (BCR)—
R-HSA-181438Toll Like Receptor 2 (TLR2) Cascade—
R-HSA-166016Toll Like Receptor 4 (TLR4) Cascade—
R-HSA-168179Toll Like Receptor TLR1:TLR2 Cascade—
R-HSA-168188Toll Like Receptor TLR6:TLR2 Cascade—
R-HSA-168898Toll-like Receptor Cascades—

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 (44): 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), 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), DNA-templated transcription (GO:0006351), mesoderm development (GO:0007498), peptidyl-tyrosine phosphorylation (GO:0018108), calcium-mediated signaling (GO:0019722), proteoglycan catabolic process (GO:0030167), 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), positive regulation of phagocytosis (GO:0050766), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), negative regulation of B cell activation (GO:0050869), monocyte proliferation (GO:0061516), negative regulation of leukocyte proliferation (GO:0070664), cellular response to molecule of fungal origin (GO:0071226), apoptotic signaling pathway (GO:0097190), 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), eosinophil homeostasis (GO:1990959), negative regulation of cytokine production (GO:0001818), immune system process (GO:0002376), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), regulation of B cell activation (GO:0050864)

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 (7): 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)

Reactome top-level categories

18 top-level categories:

CategoryPathways
GPCR downstream signalling2
Diseases associated with the TLR signaling cascade2
Antigen processing-Cross presentation1
Toll Like Receptor 4 (TLR4) Cascade1
Toll Like Receptor TLR1:TLR2 Cascade1
Toll Like Receptor TLR6:TLR2 Cascade1
Fcgamma receptor (FCGR) dependent phagocytosis1
DAP12 interactions1
Fc epsilon receptor (FCERI) signaling1
RHO GTPase Effectors1
G-protein beta:gamma signalling1
Leishmania phagocytosis1
SARS-CoV Infections1
Signaling by the B Cell Receptor (BCR)1
Class I MHC mediated antigen processing & presentation1
Immune System1
Toll-like Receptor Cascades1
Toll Like Receptor 2 (TLR2) Cascade1

GO top-level categories

showing 60 of 78 GO namespaces:

CategoryTerms
cellular anatomical structure3
cytoplasm3
positive regulation of hypersensitivity2
positive regulation of immunoglobulin mediated immune response2
anion binding2
binding2
leukocyte homeostasis1
myeloid cell homeostasis1
type III hypersensitivity1
regulation of type III hypersensitivity1
positive regulation of myeloid leukocyte mediated immunity1
regulation of type I hypersensitivity1
type I hypersensitivity1
immune response1
histamine secretion involved in inflammatory response1
mast cell degranulation1
establishment of localization in cell1
exocytic process1
immunoglobulin production1
regulation of immunoglobulin production1
positive regulation of production of molecular mediator of immune response1
B cell cytokine production1
regulation of B cell mediated immunity1
regulation of cytokine production involved in immune response1
toll-like receptor signaling pathway1
B cell apoptotic process1
regulation of lymphocyte apoptotic process1
gene expression1
RNA biosynthetic process1
tissue development1
animal gross anatomical part developmental process1
protein phosphorylation1
intracellular signaling cassette1
proteoglycan metabolic process1
glycoprotein catabolic process1
regulation of B cell proliferation1
B cell proliferation1
positive regulation of lymphocyte proliferation1
positive regulation of B cell activation1
response to molecule of bacterial origin1
response to lipid1
response to oxygen-containing compound1
negative regulation of cytokine production1
interleukin-10 production1
regulation of interleukin-10 production1
positive regulation of cytokine production1
interleukin-6 production1
regulation of interleukin-6 production1
tumor necrosis factor production1
regulation of tumor necrosis factor production1
positive regulation of tumor necrosis factor superfamily cytokine production1
response to reactive oxygen species1
cellular response to oxidative stress1
cellular response to oxygen-containing compound1
protein kinase activity1
protein tyrosine kinase activity1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
phosphatidylinositol phosphate binding1
transition metal ion binding1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 15 of 66 annotations. The rest are phylogenetic / computational / electronic (IEA).

15 experimentally-supported GO terms:

GO termNSEvidence
B cell receptor signaling pathwayBPdirect assay
intracellular signal transductionBPdirect assay
peptidyl-tyrosine phosphorylationBPdirect assay
positive regulation of NLRP3 inflammasome complex assemblyBPdirect assay
positive regulation of cGAS/STING signaling pathwayBPdirect assay
cytoplasmCCdirect assay
cytosolCCdirect assay
membrane raftCCdirect assay
plasma membraneCCdirect assay
identical protein bindingMFphysical interaction
non-membrane spanning protein tyrosine kinase activityMFdirect assay
phosphatidylinositol-3,4,5-trisphosphate bindingMFdirect assay
phospholipase activator activityMFdirect assay
phospholipase bindingMFphysical interaction
protein tyrosine kinase activityMFdirect assay

Protein interactions and networks

STRING

showing 15 of 3,142 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
BTKBLNKQ8WV28881
BTKCD79BP40259876
BTKCD79AP11912842
BTKBCRP11274822
BTKPLCG2P16885805
BTKPLEKP08567778
BTKPLEK2Q9NYT0775
BTKIBTKQ9P2D0763
BTKCARD11Q9BXL7762
BTKDCLRE1CQ96SD1744
BTKIGHV4-38-2P0DP08741
BTKCD19P15391727
BTKPIK3CDO00329719
BTKPIK3CGP48736716
BTKPIK3CAP42336715

IntAct

Human interaction partners of BTK in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 36 partners by confidence:

PartnerInteraction typeMIscoreRecords
GTF2Iphysical association0.7205
BLNKdirect interaction0.6704
HSP90AB1physical association0.6402
KATNB1physical association0.5902
MALcolocalization0.5605
MEOX2physical association0.5603
ADAM15direct interaction0.5602
ARID3Aphysical association0.5601
SH3BP5physical association0.5204
PRKCQphysical association0.5202
PIK3R3physical association0.4902
BRAFproximity0.4702
IBTKphysical association0.4602
ARdirect interaction0.4401
FASLGdirect interaction0.4401
GAB1direct interaction0.4401
METdirect interaction0.4401
PRRG4direct interaction0.4401
WASphysical association0.4004
FCER1Gphysical association0.4001
GP6physical association0.4001
MED28physical association0.4001
SFNphysical association0.4001
ARRB1physical association0.3701
BECN1physical association0.3701
MRPS22physical association0.3701
PLAUphysical association0.3701
HSP90AA1association0.3504
BLTP3Bassociation0.3501
HCKassociation0.3501

BioGRID (162 interactions; top human partners by supporting records): GTF2I (Affinity Capture-Western; 7 records), BLNK (Affinity Capture-Western; 5 records), ANKRD54 (Affinity Capture-MS; 4 records), CBL (Reconstituted Complex; 4 records), IBTK (Reconstituted Complex; 4 records), SH3BP5 (Far Western; 4 records), STAT5A (Affinity Capture-Western; 4 records), CPVL (Affinity Capture-Western; 3 records), HSP90AA1 (Affinity Capture-MS; 3 records), PRKD1 (Affinity Capture-Western; 3 records), ARID3A (Affinity Capture-Western; 2 records), CAV1 (Affinity Capture-Western; 2 records), CDC37 (Affinity Capture-MS; 2 records), GNAQ (Reconstituted Complex; 2 records), GRB2 (Two-hybrid; 2 records)

SIGNOR signaling

showing 39 of 49 signaling interactions:

AEffectBMechanism
BTK“up-regulates activity”PLCG2phosphorylation
BTKup-regulatesPLCG2phosphorylation
ibrutinibdown-regulatesBTK“chemical inhibition”
ABL1unknownBTKphosphorylation
TEC“down-regulates activity”BTKphosphorylation
SYK“up-regulates activity”BTKphosphorylation
PRKCB“down-regulates activity”BTKphosphorylation
SRC“up-regulates activity”BTKphosphorylation
ABL1“down-regulates activity”BTKphosphorylation
BTK“up-regulates activity”WASphosphorylation
AKT1“down-regulates quantity by destabilization”BTKphosphorylation
GNA12“up-regulates activity”BTKbinding
acalabrutinib“down-regulates activity”BTK“chemical inhibition”
BTK“down-regulates activity”MDM2phosphorylation
BTK“down-regulates activity”STAT3phosphorylation
JAK2“up-regulates activity”BTKphosphorylation
BTK“up-regulates activity”IKZF1phosphorylation
BTK“up-regulates activity”PLCG1phosphorylation
BTK“up-regulates activity”WIPF1phosphorylation
BTK“up-regulates quantity”CNN3phosphorylation
BTK“up-regulates activity”RELAphosphorylation
BTKup-regulatesBTKphosphorylation
LYNup-regulatesBTKphosphorylation
BTKup-regulatesGTF2Iphosphorylation
BTKunknownWASphosphorylation
BTKup-regulatesBMXphosphorylation
BTKup-regulatesITKphosphorylation
BTKup-regulatesTECphosphorylation
PIK3CA“up-regulates activity”BTKphosphorylation
PI3K“up-regulates activity”BTKphosphorylation
BTK“up-regulates activity”DDX41phosphorylation
BTK“up-regulates activity”GTF2Iphosphorylation
BTK“up-regulates activity”DAPP1phosphorylation
BTK“up-regulates activity”STAT5Aphosphorylation
ITK“down-regulates activity”BTKphosphorylation
PTPRG“down-regulates activity”BTKdephosphorylation
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”BTK“chemical inhibition”
GNAQ“up-regulates activity”BTKbinding
BTK“up-regulates activity”p38binding

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

ComplexSubunitsMembers
★ BTK-EEIG1-GAB2-PLCG2-TNFRSF11A complex5GAB2, PLCG2, TNFRSF11A, BTK, EEIG1
★ BTK-GNB1-GNG2 complex3BTK, GNB1, GNG2
★ BTK-CAV1 complex2BTK, CAV1
★ BTK-IBTK complex2BTK, IBTK

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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:

PathwayPartnersFoldFDR
MAPK1/MAPK3 signaling522.6×2e-04
Constitutive Signaling by Aberrant PI3K in Cancer521.9×2e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling620.0×5e-05
MAPK family signaling cascades517.7×3e-04
PIP3 activates AKT signaling613.8×2e-04
RAF/MAP kinase cascade612.6×3e-04
Diseases of signal transduction by growth factor receptors and second messengers611.8×3e-04
SARS-CoV Infections59.6×2e-03

GO biological processes:

GO termPartnersFoldFDR
epidermal growth factor receptor signaling pathway535.4×2e-04
intracellular signal transduction77.6×4e-03

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for BTK: 1,009 ClinVar records (369 pathogenic / likely pathogenic); 3 CIViC cancer variants. Per-variant detail is on Sugi Variant.

ClinVar

1,009 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic254
Likely pathogenic115
Uncertain significance203
Likely benign212
Benign54

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 369 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant IDHGVSClassificationReviewSubmitters
11363NM_000061.3(BTK):c.763C>T (p.Arg255Ter)Pathogeniccriteria provided, multiple submitters, no conflicts13
11348NM_000061.3(BTK):c.83G>A (p.Arg28His)Pathogeniccriteria provided, multiple submitters, no conflicts8
11377NM_000061.3(BTK):c.1558C>T (p.Arg520Ter)Pathogeniccriteria provided, multiple submitters, no conflicts7
11383NM_000061.3(BTK):c.1684C>T (p.Arg562Trp)Pathogeniccriteria provided, multiple submitters, no conflicts7
492813NM_000061.3(BTK):c.863G>A (p.Arg288Gln)Pathogeniccriteria provided, multiple submitters, no conflicts7
11378NM_000061.3(BTK):c.1559G>A (p.Arg520Gln)Pathogeniccriteria provided, multiple submitters, no conflicts6
11344NM_000061.3(BTK):c.37C>T (p.Arg13Ter)Pathogeniccriteria provided, multiple submitters, no conflicts4
279714NM_000061.3(BTK):c.1573C>T (p.Arg525Ter)Pathogeniccriteria provided, multiple submitters, no conflicts4
492818NM_000061.3(BTK):c.1581_1584del (p.Cys527fs)Pathogeniccriteria provided, multiple submitters, no conflicts4
946996NM_000061.3(BTK):c.82C>T (p.Arg28Cys)Pathogeniccriteria provided, multiple submitters, no conflicts4
11362NM_000061.3(BTK):c.755G>A (p.Trp252Ter)Pathogeniccriteria provided, multiple submitters, no conflicts3
279713NM_000061.3(BTK):c.215dup (p.Asn72fs)Pathogeniccriteria provided, multiple submitters, no conflicts3
439452NM_000061.3(BTK):c.1780G>A (p.Gly594Arg)Pathogeniccriteria provided, multiple submitters, no conflicts3
632728NM_000061.3(BTK):c.176AGA[1] (p.Lys60del)Pathogeniccriteria provided, multiple submitters, no conflicts3
632729NM_000061.3(BTK):c.588+1G>TPathogeniccriteria provided, multiple submitters, no conflicts3

Per-variant reference — Sugi Variant

Explore BTK’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,269):

Position(s)EffectΔscoreSites
X:101353352–101353353acceptor_loss1.00005
X:101353868–101353869donor_loss1.00005
X:101354628–101354629donor_loss1.00005
X:101356778donor_gain1.0000
X:101356783donor_loss1.0000
X:101357513donor_gain1.0000
X:101357584–101357585acceptor_loss1.00004
X:101358394acceptor_gain1.0000
X:101360566–101360567donor_loss1.00005
X:101360607donor_gain1.0000

AlphaMissense

2,466 missense substitutions predicted likely pathogenic (of 4,362 scored), across 506 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M50990.9840.999
M43790.9710.998
M44990.9690.999
M63090.9540.998
M45090.8750.993
M43190.8740.981
D52181.0001.000
D53981.0001.000
H33380.9991.000
N52680.9991.000
D57980.9991.000
H51980.9981.000
H14380.9971.000
F54080.9971.000
H36280.9961.000
F44280.9941.000
F3080.9921.000
N2480.9911.000
D23280.9880.995
F64480.9860.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

CancerPrognosticp-value
Lung Adenocarcinoma (TCGA)favorable1.03e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)favorable0.000357

Disease associations

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

GenCC curated gene-disease

3 curated gene-disease records:

DiseaseClassificationInheritanceRecords
Bruton-type agammaglobulinemiaDefinitiveX-linked3
isolated growth hormone deficiency type IIIStrongX-linked3
short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemiaSupportiveX-linked

ClinGen Gene-Disease Validity

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

2 validity classifications:

DiseaseClassificationInheritance
isolated growth hormone deficiency type IIIDisputedXL
Bruton-type agammaglobulinemiaDefinitiveXL

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

PanelRating
Agammaglobulinaemia with absent BTK expressiongreen
COVID-19 researchgreen
Infantile enterocolitis & monogenic inflammatory bowel diseasegreen
Pituitary hormone deficiencygreen
Primary immunodeficiency or monogenic inflammatory bowel diseasegreen

Mondo (7): Bruton-type agammaglobulinemia (MONDO:0010421), isolated growth hormone deficiency type III (MONDO:0010615), autosomal recessive agammaglobulinemia 1 (MONDO:0020729), deafness dystonia syndrome (MONDO:0010578), Fabry disease (MONDO:0010526), common variable immunodeficiency (MONDO:0015517), short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia (MONDO:0018967)

Orphanet (7): Non-syndromic agammaglobulinemia (Orphanet:229717), Isolated growth hormone deficiency type III (Orphanet:231692), X-linked agammaglobulinemia (Orphanet:47), Non-acquired isolated growth hormone deficiency (Orphanet:631), Mohr-Tranebjaerg syndrome (Orphanet:52368), Fabry disease (Orphanet:324), OBSOLETE: Common variable immunodeficiency (Orphanet:1572)

HPO phenotypes

showing 60 of 77 phenotypes (HPO-id order):

HPOTerm
HP:0000010Recurrent urinary tract infections
HP:0000024Prostatitis
HP:0000031Epididymitis
HP:0000162Glossoptosis
HP:0000246Sinusitis
HP:0000365Hearing impairment
HP:0000389Chronic otitis media
HP:0000403Recurrent otitis media
HP:0000407Sensorineural hearing impairment
HP:0000509Conjunctivitis
HP:0000750Delayed speech and language development
HP:0000823Delayed puberty
HP:0000824Decreased response to growth hormone stimulation test
HP:0000988Skin rash
HP:0000999Pyoderma
HP:0001053Hypopigmented skin patches
HP:0001287Meningitis
HP:0001369Arthritis
HP:0001402Hepatocellular carcinoma
HP:0001412Enteroviral hepatitis
HP:0001419X-linked recessive inheritance
HP:0001508Failure to thrive
HP:0001596Alopecia
HP:0001648Cor pulmonale
HP:0001824Weight loss
HP:0001873Thrombocytopenia
HP:0001875Decreased total neutrophil count
HP:0001903Anemia
HP:0001945Fever
HP:0002014Diarrhea
HP:0002024Malabsorption
HP:0002028Chronic diarrhea
HP:0002088Abnormal lung morphology
HP:0002090Pneumonia
HP:0002110Bronchiectasis
HP:0002383Infectious encephalitis
HP:0002664Neoplasm
HP:0002718Recurrent bacterial infections
HP:0002719Recurrent infections
HP:0002720Decreased circulating IgA concentration
HP:0002721Immunodeficiency
HP:0002732Lymph node hypoplasia
HP:0002743Recurrent enteroviral infections
HP:0002750Delayed skeletal maturation
HP:0002754Osteomyelitis
HP:0002783Recurrent lower respiratory tract infections
HP:0002850Decreased circulating IgM concentration
HP:0002901Hypocalcemia
HP:0002960Autoimmunity
HP:0003095Septic arthritis
HP:0003139Panhypogammaglobulinemia
HP:0003593Infantile onset
HP:0003621Juvenile onset
HP:0003623Neonatal onset
HP:0003729Enteroviral dermatomyositis syndrome
HP:0004315Decreased circulating IgG concentration
HP:0004322Short stature
HP:0004432Agammaglobulinemia
HP:0005403Decreased total T cell count
HP:0005479Decreased circulating IgE concentration

MeSH disease descriptors

5 disease descriptors:

DescriptorNameTree numbers
D017074Common Variable ImmunodeficiencyC20.673.330
D000795Fabry DiseaseC10.228.140.163.100.435.825.200; 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
C537409Bruton type agammaglobulinemia *(supp.)*
C537149Hypogammaglobulinemia and Isolated growth hormone deficiency, X-linked *(supp.)*
C535808Mohr-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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the BTK protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

19 curated-mechanism drugs:

DrugModalityMax phase
ACALABRUTINIBSmall molecule4
IBRUTINIBSmall molecule4
PIRTOBRUTINIBSmall molecule4
TIRABRUTINIBSmall molecule4
ZANUBRUTINIBSmall molecule4
ABIVERTINIBSmall molecule3
EVOBRUTINIBSmall molecule3
FENEBRUTINIBSmall molecule3
ORELABRUTINIBSmall molecule3
RILZABRUTINIBSmall molecule3
TOLEBRUTINIBSmall molecule3
BMS-986142Small molecule2
BRANEBRUTINIBSmall molecule2
EDRALBRUTINIBSmall molecule2
ELSUBRUTINIBSmall molecule2
POSELTINIBSmall molecule2
SPEBRUTINIB BESYLATESmall molecule2
VECABRUTINIBSmall molecule2
MSC-2364447Unknown1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes BTK — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

DrugTarget (ChEMBL)MembersMax phase
RITLECITINIBTEC family kinase54

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 279,759 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 84 molecules by phase:

MoleculeNamePhasePatents
CHEMBL3707348ACALABRUTINIB44,772
CHEMBL1873475IBRUTINIB48,363
CHEMBL4650485PIRTOBRUTINIB4485
CHEMBL4071161TIRABRUTINIB42,261
CHEMBL3936761ZANUBRUTINIB42,664
CHEMBL288441BOSUTINIB412,869
CHEMBL3545311BRIGATINIB45,988
CHEMBL2403108CERITINIB49,002
CHEMBL601719CRIZOTINIB415,133
CHEMBL5416410DASATINIB4674
CHEMBL1983268ENTRECTINIB43,737
CHEMBL1287853FEDRATINIB43,770
CHEMBL3701238FUTIBATINIB4874
CHEMBL58MITOXANTRONE4168,731
CHEMBL180022NERATINIB49,891
CHEMBL502835NINTEDANIB48,978
CHEMBL3786343OLMUTINIB41,900
CHEMBL3353410OSIMERTINIB49,448
CHEMBL1171837PONATINIB49,435
CHEMBL4085457RITLECITINIB4784
CHEMBL535SUNITINIB4
CHEMBL24828VANDETANIB4
CHEMBL4297865ABIVERTINIB3
CHEMBL4072833EVOBRUTINIB3
CHEMBL4065122FENEBRUTINIB3
CHEMBL4650321ORELABRUTINIB3
CHEMBL3702854RILZABRUTINIB3
CHEMBL4650323TOLEBRUTINIB3
CHEMBL483158ALISERTIB3
CHEMBL31965CANERTINIB3
CHEMBL491473CEDIRANIB3
CHEMBL522892DOVITINIB3
CHEMBL3265032ENTOSPLETINIB3
CHEMBL603469LESTAURTINIB3
CHEMBL4756476NEMTABRUTINIB3
CHEMBL3545154POZIOTINIB3
CHEMBL3647420PYROTINIB3
CHEMBL4483575REMIBRUTINIB3
CHEMBL3545308ROCILETINIB3
CHEMBL217092SARACATINIB3
CHEMBL3544983TESEVATINIB3
CHEMBL3900554BMS-9861422
CHEMBL4297674BRANEBRUTINIB2
CHEMBL4650338EDRALBRUTINIB2
CHEMBL4594348ELSUBRUTINIB2
CHEMBL4163691POSELTINIB2
CHEMBL3301625SPEBRUTINIB2
CHEMBL4297640VECABRUTINIB2
CHEMBL1922094APITOLISIB2
CHEMBL495727AT-92832
CHEMBL4114766ATUZABRUTINIB2
CHEMBL5083772BIIB-0912
CHEMBL575448BMS-7548072
CHEMBL4094440BMS-9193732
CHEMBL1967878CENISERTIB2
CHEMBL2010872CEP-119812
CHEMBL402548DANUSERTIB2
CHEMBL215152DEFOSBARASERTIB2
CHEMBL1230609FORETINIB2
CHEMBL1980297ILORASERTIB2

Clinical evidence (CIViC)

Drug × variant × indication, from 3 curated evidence items; also 1 oncogenic, 1 prognostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

2 predictive associations by evidence level:

VariantTherapyIndicationEffectLevelCIViC
BTK C481SIbrutinibChronic Lymphocytic LeukemiaResistanceCIViC BEID1770 +1
BTK T316AIbrutinibChronic Lymphocytic LeukemiaResistanceCIViC CEID1985

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (3)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

C481S (missense variant), MUTATION, T316A (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Tec family

Most potent curated ligand interactions (56 total), top 25:

LigandActionAffinityParameter
corubrutinibInhibition10.15pKd
luxeptinibInhibition10.0pIC50
branebrutinibInhibition9.96pIC50
BIIB129Inhibition9.52pIC50
RN486Inhibition9.51pKd
sofnobrutinibInhibition9.41pIC50
abivertinibInhibition9.4pIC50
spebrutinibInhibition9.3pIC50
BMS-986142Inhibition9.3pIC50
compound 4g [PMID: 30893553]Inhibition9.28pIC50
BTK inhibitor 16 [PMID: 30122225]Inhibition9.15pIC50
vecabrutinibInhibition9.14pIC50
midobrutinibInhibition9.09pIC50
milrebrutinibInhibition9.07pIC50
birelentinibInhibition9.07pIC50
remibrutinibInhibition9.0pIC50
BIIB068Inhibition9.0pIC50
ZYBT1Irreversible inhibition9.0pIC50
compound 71 [WO2018191577A1]Inhibition9.0pIC50
CNX-774Inhibition9.0pIC50
ibrutinibInhibition8.82pIC50
rilzabrutinibInhibition8.82pIC50
CGI1746Inhibition8.72pIC50
compound 9 [PMID: 26006010]Inhibition8.72pIC50
compound 36 [PMID: 21958547]Inhibition8.71pIC50

Binding affinities (BindingDB)

4172 measured of 6098 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
4-(2-acryloyl-1,2,3,4- tetrahydroisoquinolin- 5-yl)-6-chloro-3-fluoro- 9H-carbazole-1- carboxamideIC500.00026 nMUS-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- carboxamideIC500.0003 nMUS-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- carboxamideIC500.0003 nMUS-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- carboxamideIC500.0006 nMUS-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- carboxamideIC500.029 nMUS-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-carboxamideIC500.04 nMUS-9688629: Indole carboxamide compounds
5-fluoro-2,3-dimethyl-4-(2-prop-2-enoyl-3,4-dihydro-1H-isoquinolin-8-yl)-1H-indole-7-carboxamideIC500.04 nMUS-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)IC500.045 nMUS-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
4-[3-(ethenylsulfonylamino)phenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamideIC500.046 nMUS-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-carboxamideIC500.047 nMUS-10676434: 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-carboxamideIC500.047 nMUS-10266491: Carbazole derivatives
3-fluoro-4-(1-prop-2-enoyl-2,3-dihydroindol-6-yl)-9H-carbazole-1-carboxamideIC500.049 nMUS-10266491: Carbazole derivatives
4-[(3S)-3-(3-cyclopropylprop-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamideIC500.05 nMUS-9688629: Indole carboxamide compounds
5-fluoro-2,3-dimethyl-4-(1-prop-2-enoylpiperidin-3-yl)-1H-indole-7-carboxamideIC500.05 nMUS-9688629: Indole carboxamide compounds
1-(3-chloro-2,6-difluorophenyl)-3-[3-fluoro-4-[7-(5-methyl-1H-imidazol-2-yl)-1-oxo-2,3-dihydroisoindol-4-yl]phenyl]ureaIC500.05 nMUS-10604508: 2,3-dihydro-isoindole-1-one derivative as BTK kinase suppressant, and pharmaceutical composition including same
3-fluoro-4-(1-prop-2-enoylpiperidin-3-yl)-9H-carbazole-1-carboxamideIC500.05 nMUS-10266491: Carbazole derivatives
3-fluoro-4-(1-prop-2-enoyl-3,6-dihydro-2H-pyridin-5-yl)-7-(trifluoromethyl)-9H-carbazole-1-carboxamideIC500.05 nMUS-10266491: Carbazole derivatives
4-[3-(ethenylsulfonylamino)phenyl]-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamideIC500.051 nMUS-10266491: Carbazole derivatives
4-[(3S)-3-(3-cyclopropylprop-2-ynoylamino)piperidin-1-yl]-3-fluoro-9H-carbazole-1-carboxamideIC500.052 nMUS-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]benzamideIC500.058 nMUS-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-carboxamideIC500.06 nMUS-9688629: Indole carboxamide compounds
5-fluoro-4-[(3S)-3-(hex-2-ynoylamino)piperidin-1-yl]-2,3-dimethyl-1H-indole-7-carboxamideIC500.06 nMUS-9688629: Indole carboxamide compounds
3-fluoro-7-(2-hydroxypropan-2-yl)-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-9H-carbazole-1-carboxamideIC500.061 nMUS-10266491: Carbazole derivatives
4-(2-Acryloyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-3-fluoro-9H-carbazole-1-carboxamide (Single Enantiomeric Atropisomer)IC500.067 nMUS-10023534: Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK
4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-3-fluoro-9H-carbazole-1-carboxamideIC500.067 nMUS-10266491: Carbazole derivatives
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-2,3-dimethyl-1H-indole-7-carboxamideIC500.068 nMUS-9688629: Indole carboxamide compounds
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamideIC500.069 nMUS-10266491: Carbazole derivatives
4-[3-[ethenylsulfonyl(methyl)amino]-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamideIC500.07 nMUS-9802915: Indole carboxamide compounds
5-fluoro-2,3-dimethyl-4-[(3S)-3-(prop-2-ynoylamino)piperidin-1-yl]-1H-indole-7-carboxamideIC500.07 nMUS-9688629: Indole carboxamide compounds
1-(2-chloro-3,6-difluorophenyl)-3-[3-fluoro-4-[7-(5-methyl-1H-imidazol-2-yl)-1-oxo-2,3-dihydroisoindol-4-yl]phenyl]ureaIC500.07 nMUS-10604508: 2,3-dihydro-isoindole-1-one 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)-oneIC500.07 nMUS-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-oneIC500.07 nMUS-10214546
Cis-4-(1-acryloylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-3-fluoro-9H-carbazole-1-carboxamideIC500.07 nMUS-10266491: Carbazole derivatives
3-fluoro-4-(4-prop-2-enoyl-2,3-dihydro-1,4-benzothiazin-8-yl)-9H-carbazole-1-carboxamideIC500.073 nMUS-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-oneIC500.073 nMUS-10246457: Indazole and azaindazole Btk inhibitors
3-fluoro-4-[(3S)-3-(prop-2-enoylamino)piperidin-1-yl]-9H-carbazole-1-carboxamideIC500.073 nMUS-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]benzamideIC500.075 nMUS-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-carboxamideIC500.075 nMUS-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-dicarboxamideIC500.075 nMUS-10266491: Carbazole derivatives
7-cyano-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-9H-carbazole-1-carboxamideIC500.076 nMUS-10266491: Carbazole derivatives
4-[3-(ethenylsulfonylamino)phenyl]-2,3-dimethyl-1H-indole-7-carboxamideIC500.077 nMUS-9688629: Indole carboxamide compounds
3-chloro-7-(hydroxymethyl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamideIC500.078 nMUS-10266491: Carbazole derivatives
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamideIC500.079 nMUS-10266491: Carbazole derivatives
5-fluoro-4-(4-fluoro-2-prop-2-enoyl-3,4-dihydro-1H-isoquinolin-5-yl)-2,3-dimethyl-1H-indole-7-carboxamideIC500.08 nMUS-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]benzamideIC500.081 nMUS-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]benzamideIC500.083 nMUS-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]benzamideIC500.085 nMUS-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
7-(1,2-dihydroxyethyl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-9H-carbazole-1-carboxamideIC500.088 nMUS-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-carboxamideIC500.09 nMUS-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-carboxamideIC500.09 nMUS-8729078: Inhibitors of bruton’s tyrosine kinase

ChEMBL bioactivities

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

pChemblTypeValueUnitMolecule
10.85IC500.014nMCHEMBL4762397
10.54IC500.029nMCHEMBL5977366
10.40IC500.04nMCHEMBL5826570
10.40IC500.04nMCHEMBL5945342
10.35IC500.045nMCHEMBL5884405
10.34IC500.046nMCHEMBL5909954
10.33IC500.047nMCHEMBL5789446
10.31IC500.049nMCHEMBL5749648
10.30IC500.05nMCHEMBL5741138
10.30IC500.05nMCHEMBL5824452
10.30IC500.05nMCHEMBL6004055
10.30IC500.05nMCHEMBL5858594
10.30IC500.05nMCHEMBL5799170
10.29IC500.051nMCHEMBL5772754
10.28IC500.052nMCHEMBL5824452
10.28IC500.052nMCHEMBL5848923
10.24IC500.058nMCHEMBL4113670
10.22IC500.06nMCHEMBL5993286
10.22IC500.06nMCHEMBL5836429
10.21IC500.061nMCHEMBL5983201
10.17IC500.068nMCHEMBL4237999
10.17IC500.067nMCHEMBL5745824
10.17IC500.067nMCHEMBL6042416
10.16IC500.069nMCHEMBL5819531
10.15IC500.07nMCHEMBL4648442
10.15Kd0.07nMBIIB-091
10.15IC500.07nMCHEMBL4237999
10.15IC500.07nMCHEMBL5820093
10.15IC500.07nMCHEMBL4246324
10.15IC500.07nMCHEMBL5995250
10.15IC500.07nMCHEMBL5888728
10.15IC500.07nMCHEMBL6042416
10.15IC500.07nMCHEMBL5862023
10.15IC500.07nMCHEMBL5757954
10.14IC500.073nMCHEMBL5850088
10.14IC500.073nMCHEMBL5962240
10.14IC500.073nMCHEMBL5808322
10.12IC500.075nMCHEMBL4113445
10.12IC500.075nMCHEMBL5938181
10.12IC500.076nMCHEMBL5958946
10.12IC500.075nMCHEMBL6053298

PubChem BioAssay actives

2606 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.

CompoundAssayTypeValueUnit
4-tert-butyl-N-[2-methyl-3-[5-[[methyl(prop-2-enoyl)amino]methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]phenyl]benzamide1673837: Inhibition of full length human unphosphorylated BTK using FITC-Ahx-TSELKKVVALYDYMPMNAND-NH2 as substrate incubated for 60 mins in presence of ATP at Km concentrationic50<0.0001uM
4-(4-phenoxyphenyl)-10-prop-2-enoyl-2,3,7,10-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),4,6-triene-5-carboxamide1615344: 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 assayic500.0001uM
4-(4-phenoxyphenyl)-12-prop-2-enoyl-2,3,7,12-tetrazatricyclo[6.5.0.02,6]trideca-1(8),4,6-triene-5-carboxamide1615344: 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 assayic500.0001uM
6-(4-phenoxyphenyl)-3-(1-prop-2-enoylpiperidin-4-yl)-5H-imidazo[1,2-b]pyrazole-7-carboxamide1615344: 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 assayic500.0001uM
6-[(7S)-7-(prop-2-enoylamino)-5-azaspiro[2.4]heptan-5-yl]-2-[4-(2-pyrrolidin-1-ylethyl)anilino]pyridine-3-carboxamide1418272: 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 assayic500.0001uM
4-[6-(4-methoxybut-2-ynoylamino)quinolin-4-yl]oxy-N-pyridin-2-ylbenzamide1720508: 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 assayic500.0001uM
4-[3-(ethenylsulfonylamino)phenyl]-2,3-dimethyl-1H-indole-7-carboxamide1399226: 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 assayic500.0001uM
4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide1656238: Inhibition of recombinant human BTK using fluoresceinated peptide as substrate after 60 mins fluorescence assayic500.0001uM
5-fluoro-2,3-dimethyl-4-[(3S)-3-(prop-2-ynoylamino)piperidin-1-yl]-1H-indole-7-carboxamide1656238: Inhibition of recombinant human BTK using fluoresceinated peptide as substrate after 60 mins fluorescence assayic500.0001uM
4-[3-[ethenylsulfonyl(methyl)amino]-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide1399226: 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 assayic500.0001uM
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-2,3-dimethyl-1H-indole-7-carboxamide1399226: 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 assayic500.0001uM
2,3-dimethyl-4-[(3S)-3-(prop-2-ynoylamino)piperidin-1-yl]-1H-indole-7-carboxamide1656238: Inhibition of recombinant human BTK using fluoresceinated peptide as substrate after 60 mins fluorescence assayic500.0001uM
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-2,3-dimethyl-1H-indole-7-carboxamide1399226: 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 assayic500.0001uM
4-[8-amino-1-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridinyl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]cubane-1-carboxylic acid1432830: 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 assayic500.0001uM
(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 acid1432830: 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 assayic500.0001uM
4-[3-(ethenylsulfonylamino)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide1399226: 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 assayic500.0001uM
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-carboxamide1820528: Binding affinity to wild-type human full length BTK (M1 to S659 residues) expressed in mammalian expression system by Kinomescan methodkd0.0001uM
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 acid1432830: 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 assayic500.0001uM
2-[3-(2-amino-6-pyridin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one1830219: Inhibition of human BTK-A using phosphorylated substrate in presence of ATP by microplate reader assayic500.0001uM
2-[(6-methyl-3-pyridinyl)amino]-6-[(1R,4R)-5-prop-2-enoyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridine-3-carboxamide1418272: 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 assayic500.0001uM
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]benzamide1711650: 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 assayic500.0001uM
(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-carboxamide1820500: Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assayic500.0001uM
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-one1937987: Reversible inhibition of human BTKic500.0001uM
Ibrutinib1465438: Inhibition of human BTK using KVEKIGEGTYGVVYK as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition by filter binding methodic500.0001uM
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-carboxamide1615344: 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 assayic500.0002uM
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-carboxamide1678386: 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 assayic500.0002uM
N-[3-[6-amino-5-[2-[methyl(prop-2-enoyl)amino]ethoxy]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]-4-cyclopropyl-2-fluorobenzamide1878117: Binding affinity to BTK (unknown origin) assessed as dissociation constant by KINOMEscan analysiskd0.0002uM
3-tert-butyl-N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]pyrrolidine-1-carboxamide1696245: 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 assayic500.0002uM
2,3-dimethyl-4-[3-(prop-2-enoylamino)phenyl]-1H-indole-7-carboxamide1399226: 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 assayic500.0002uM
2,3-dimethyl-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-1H-indole-7-carboxamide1399226: 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 assayic500.0002uM
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 acid1432830: 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 assayic500.0002uM
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 acid1432830: 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 assayic500.0002uM
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 acid1432830: 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 assayic500.0002uM
2-[3-[6-amino-2-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one1368714: 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 assayic500.0002uM
2-[3-[6-amino-2-[(1-propan-2-ylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one1368714: 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 assayic500.0002uM
7-(2-hydroxypropan-2-yl)-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-9H-carbazole-1-carboxamide1399226: 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 assayic500.0002uM
7-(2-hydroxypropan-2-yl)-4-[3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide1399226: 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 assayic500.0002uM
7-(2-hydroxypropan-2-yl)-4-[3-[methyl(prop-2-enoyl)amino]phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide1399226: 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 assayic500.0002uM
4-[3-[ethenylsulfonyl(methyl)amino]phenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide1399226: 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 assayic500.0002uM
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(prop-2-enoylamino)phenyl]-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide1399226: 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 assayic500.0002uM
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-carboxamide1820500: Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assayic500.0002uM
2-(4-phenoxyphenyl)-7-[(prop-2-enoylamino)methyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide1615344: 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 assayic500.0002uM
oxolan-2-ylmethyl 2-[4-[[5-chloro-4-[3-(prop-2-enoylamino)anilino]pyrimidin-2-yl]amino]phenoxy]acetate1426139: 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 assayic500.0002uM
4-[8-amino-3-[(1R,3S)-3-carbamoylcyclohexyl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide1432830: 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 assayic500.0002uM
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-carboxamide1763450: Inhibition of BTK (unknown origin)ic500.0002uM
1-[(3R)-3-[3-(4-phenoxyphenyl)indazol-1-yl]piperidin-1-yl]prop-2-en-1-one1576940: 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 Assayic500.0002uM
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]benzamide1711650: 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 assayic500.0002uM
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]benzamide1711650: 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 assayic500.0002uM
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]benzamide1711650: 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 assayic500.0002uM
N-[2-[4-amino-6-[3-methyl-4-[[4-(2-methylpropyl)-2-oxopiperazin-1-yl]methyl]phenyl]pyrimidin-5-yl]oxyethyl]-N-methylprop-2-enamide1878101: Inhibition of BTK (unknown origin)ic500.0002uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
rilzabrutinibaffects binding, decreases activity, decreases phosphorylation6
ibrutinibincreases reaction, decreases activity, decreases response to substance, affects binding, decreases expression (+1 more)6
(+)-JQ1 compounddecreases expression, decreases phosphorylation, increases reaction, increases expression3
Benzo(a)pyreneincreases expression, increases mutagenesis, affects methylation3
Dasatinibaffects binding, decreases activity, decreases phosphorylation2
Resveratrolaffects cotreatment, increases expression, affects binding, decreases reaction, increases reaction (+1 more)2
fenebrutinibdecreases activity1
evobrutinibaffects binding, decreases activity1
remibrutinibaffects binding, decreases activity1
orelabrutinibaffects binding, decreases activity1
2,4,6-tribromophenoldecreases expression1
bisphenol Adecreases expression1
decabromobiphenyl etherdecreases expression1
tetrabromobisphenol Adecreases expression1
benzo(e)pyreneincreases methylation1
CGP 52608affects binding, increases reaction1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
pyrachlostrobindecreases expression1
pentabrominated diphenyl ether 100decreases expression1
hexabrominated diphenyl ether 153decreases expression1
bisphenol Sincreases expression1
GSK1210151Adecreases expression, decreases phosphorylation1
methylsulfonyl benzothiazoleaffects binding1
Sunitinibincreases expression1
Arsenic Trioxideincreases expression1
Leflunomidedecreases expression1
Air Pollutantsincreases abundance, increases expression1
Copperaffects binding, decreases expression1
Disulfiramaffects binding, decreases expression1
Estradiolincreases expression1

ChEMBL screening assays

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

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4349424BindingProtac activity at E3 ubiquitin ligase/BTK in human NAMALWA cells assessed as BTK degradationSmall molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation. — *Eur J Med Chem*
CHEMBL1963733FunctionalPUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: BTKPubChem BioAssay data set
CHEMBL4407571ADMETInhibition 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 controlOptimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase. — *J Med Chem*

Cellosaurus cell lines

22 cell lines: 17 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):

CellosaurusNameCategorySex
CVCL_2Z01ID00001Transformed cell lineMale
CVCL_2Z21ID00035Transformed cell lineMale
CVCL_A4XGSDQLCHi039-AInduced pluripotent stem cellMale
CVCL_B7WBAbcam Raji BTK KOCancer cell lineMale
CVCL_B9WUAbcam THP-1 BTK KOCancer cell lineMale
CVCL_C3ESNK-NJCancer cell lineMale
CVCL_C6YVAbcam PC-3 BTK KOCancer cell lineMale
CVCL_E1E7Ubigene U-2932 BTK KOCancer cell lineFemale
CVCL_E8IZTMD8-BTK-A428D-KI-1B4Cancer cell lineMale
CVCL_E8J0TMD8-BTK-C481F-KICancer cell lineMale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 276 trials:

NCTPhaseStatusTitle
NCT01289847Phase 4COMPLETEDA Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT00074984Phase 4COMPLETEDA Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) as Compared to Placebo in Patients With Advanced Fabry Disease
NCT00081497Phase 4COMPLETEDA Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
NCT00097890Phase 4COMPLETEDReplagal Enzyme Replacement Therapy for Adults With Fabry Disease
NCT00140621Phase 4COMPLETEDA Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease
NCT00230607Phase 4TERMINATEDStudy of the Effects of Fabrazyme Treatment on Lactation and Infants
NCT00312767Phase 4WITHDRAWNA Study in Patients With Fabry Disease Who Are on Chronic Hemodialysis Therapy for Treatment of End-stage Renal Insufficiency.
NCT00487630Phase 4UNKNOWNEvaluation of Efficacy and Safety of Agalsidase Beta in Heterozygous Females for Fabry Disease
NCT01650779Phase 4COMPLETEDA Study Evaluating Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta
NCT01997489Phase 4COMPLETEDOphthalmic Findings During 10-year Enzyme Substitution of Danish Fabry Patients.
NCT04143958Phase 4WITHDRAWNTo 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
NCT05054387Phase 4COMPLETEDChina Post-marketing Surveillance (PMS) Study of Fabrazyme®
NCT05067868Phase 4RECRUITINGA Study of Replagal in Children and Adults With Fabry Disease in India
NCT06019728Phase 4COMPLETEDA Prospective Study to Investigate Safety and Tolerability of Shorter Infusion of Fabrazyme
NCT00520494Phase 4COMPLETEDEfficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01946906Phase 4COMPLETEDThe Rifaximin Study in CVID
NCT05193552Phase 4RECRUITINGUsage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00542997Phase 3COMPLETEDStudy of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT00074971Phase 3COMPLETEDA Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
NCT00701415Phase 3COMPLETEDA Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
NCT00864851Phase 3COMPLETEDSafety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease
NCT00925301Phase 3COMPLETEDStudy of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
NCT01124643Phase 3COMPLETEDExtension Study of TKT028 Evaluating Safety and Clinical Outcomes of Replagal® in Adult Patients With Fabry Disease
NCT01218659Phase 3COMPLETEDStudy to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease
NCT01298141Phase 3COMPLETEDA Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease
NCT01458119Phase 3TERMINATEDOpen-Label Phase 3 Long-Term Safety Study of Migalastat
NCT02194985Phase 3COMPLETEDOpen-Label Extension Study of the Long-Term Effects of Migalastat HCL in Patients With Fabry Disease
NCT02795676Phase 3COMPLETEDStudy of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function
NCT02921620Phase 3WITHDRAWNStudy to Evaluate the Safety and EffIcacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry Disease
NCT03018730Phase 3COMPLETEDSafety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
NCT03180840Phase 3COMPLETEDSafety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks
NCT03425539Phase 3COMPLETEDEfficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease
NCT03500094Phase 3COMPLETEDSafety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)
NCT03566017Phase 3COMPLETEDOpen Label Extension Study of 1 mg/kg Pegunigalsidase Alfa Every 2 Weeks in Patients With Fabry Disease
NCT03614234Phase 3COMPLETEDOpen Label Extension of 2 mg/kg Pegunigalsidase Alfa (PRX-102) Every 4 Weeks in Adult Fabry Disease Patients
NCT03737214Phase 3ACTIVE_NOT_RECRUITINGA Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease
NCT04020055Phase 3ACTIVE_NOT_RECRUITINGA Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variant and Renal Disease
NCT04049760Phase 3COMPLETEDSafety, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged >12 Years) With Fabry Disease
NCT04840667Phase 3TERMINATEDA Study of Replagal in Treatment-naïve Adults With Fabry Disease
NCT04974749Phase 3COMPLETEDA Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease
NCT05206773Phase 3ACTIVE_NOT_RECRUITINGA Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease
NCT05280548Phase 3ACTIVE_NOT_RECRUITINGA Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease
NCT05843916Phase 3COMPLETEDSwitch Over Study of Biosimilar Agalsidase Beta for Fabry Disease
NCT06081062Phase 3UNKNOWNEvaluate the Safety and Efficacy of Fabagal® (Agalsidase Beta) in Patients With Fabry Disease
NCT06904261Phase 3RECRUITINGA Study of Migalastat in Pediatric Subjects (2 to <12 Yrs) With Fabry Disease and Amenable GLA Variants
NCT07778667Phase 3NOT_YET_RECRUITINGA Study to Learn How Well Lucerastat Works and How Safe it is in Untreated Adult Male Participants With Fabry Disease
NCT00168012Phase 3COMPLETEDEfficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025Phase 3COMPLETEDEfficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766Phase 3COMPLETEDRapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556Phase 3COMPLETEDSafety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT01884311Phase 3COMPLETEDPharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143Phase 3COMPLETEDBioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141Phase 3COMPLETEDA Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT01821781Phase 2ACTIVE_NOT_RECRUITINGImmune Disorder HSCT Protocol
NCT02281006Phase 2TERMINATEDEfficacy of Trans-tympanic Injections of a Sodium Thiosulfate Gel to Prevent Cisplatin-induced Ototoxicity
NCT00048906Phase 2COMPLETEDAlpha-Galactosidase A Replacement Therapy for Fabry Disease
NCT00068107Phase 2COMPLETEDDosing Study of Replagal in Patients With Fabry Disease
NCT00071877Phase 2COMPLETEDAn Open-Label Clinical Trial of Replagal Enzyme Therapy in Children Ages 7-17 Years With Fabry Disease
NCT00074958Phase 2COMPLETEDA Study of Fabrazyme in Pediatric Patients With Fabry Disease
NCT00075244Phase 2COMPLETEDAlternative Dosing and Regimen of Replagal to Treat Fabry Disease

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BTK across ~30M SureChEMBL compounds — explore on Sugi Predict.

About this page

Built deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source. Provided for research and reference, not medical advice or a diagnosis. Data may be incomplete, especially for rare conditions. Consult a qualified clinician.

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Sources 99

This page pulls from 99 datasets indexed by BioBTree:

alliance_phenotypealphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruscellphonedbchembl_activitychembl_assaychembl_documentchembl_mechanismchembl_moleculechembl_targetciviccivic_assertioncivic_evidencecivic_variantclingen_dosageclingen_gene_validityclingen_variantclinical_trialsclinvarcollectricorumctd_gene_interactiondepmapdepmap_dependencydiamond_similarityefoensemblentrezexonfantom5_genefantom5_promotergenccgenerifgnomad_constraintgnomad_rmcgogoparentgtex_egenegtopdbgtopdb_interactiongwasgwas_studyhgnchpahpa_expressionhpa_pathologyhpointactinterprointogenjasparmeshmgimimmirdbmondomsigdbneighborentrezorphanetorthologorthologentrezpanelapp_geneparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_var_annotationpharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontaxonomytranscriptufeatureuniprot