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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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BTK
Bruton tyrosine kinase
Chromosome X Β· Xq22.1
NCBI Gene: 695Ensembl: ENSG00000010671.18HGNC: HGNC:1133UniProt: Q06187
374PubMed Papers
22Diseases
24Drugs
346Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneKinaseTranscription Factor
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
identical protein bindingplasma membraneB cell receptor signaling pathwaycytosolX-linked agammaglobulinemiaisolated growth hormone deficiency type IIINon-acquired isolated growth hormone deficiencychronic lymphocytic leukemia
✦AI Summary

Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase essential for B lymphocyte development and signaling 1. Upon B-cell antigen receptor (BCR) engagement, BTK phosphorylates phospholipase C gamma 2 (PLCG2) in cooperation with adapter protein BLNK, triggering downstream calcium mobilization and protein kinase C activation 2. BTK functions as a signaling platform coordinating diverse proteins and participates in toll-like receptor (TLR) pathways, acting as a critical regulator of TLR9 activation in splenic B cells 3. Within TLR signaling, BTK induces TIRAP phosphorylation and degradation, and activates NF-ΞΊB to regulate hundreds of genes 1. BTK also phosphorylates NLRP3 to promote inflammasome assembly 4 and phosphorylates DDX41 to mediate STING1-dependent type I interferon responses 5. BTK regulates transcription factors including GTF2I, ARID3A, and NFAT, though it does not directly bind DNA 67. Clinically, BTK inhibitors have revolutionized treatment of chrX lymphocytic leukemia and other B-cell lymphomas 8, with newer noncovalent inhibitors like pirtobrutinib overcoming C481 mutation-mediated resistance 9. BTK inhibition is also being investigated for multiple sclerosis, where BTK expression in microglia and B cells contributes to CNS neuroinflammation 1011.

Sources cited
1
Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase essential for B lymphocyte development and signaling .
PMID: 19290921
2
Upon B-cell antigen receptor (BCR) engagement, BTK phosphorylates phospholipase C gamma 2 (PLCG2) in cooperation with adapter protein BLNK, triggering downstream calcium mobilization and protein kinase C activation .
PMID: 11606584
3
BTK functions as a signaling platform coordinating diverse proteins and participates in toll-like receptor (TLR) pathways, acting as a critical regulator of TLR9 activation in splenic B cells .
PMID: 16517732
4
BTK also phosphorylates NLRP3 to promote inflammasome assembly and phosphorylates DDX41 to mediate STING1-dependent type I interferon responses .
PMID: 34554188
5
BTK also phosphorylates NLRP3 to promote inflammasome assembly and phosphorylates DDX41 to mediate STING1-dependent type I interferon responses .
PMID: 25704810
6
BTK regulates transcription factors including GTF2I, ARID3A, and NFAT, though it does not directly bind DNA , .
PMID: 9012831
7
BTK regulates transcription factors including GTF2I, ARID3A, and NFAT, though it does not directly bind DNA , .
PMID: 16738337
8
Clinically, BTK inhibitors have revolutionized treatment of chrX lymphocytic leukemia and other B-cell lymphomas , with newer noncovalent inhibitors like pirtobrutinib overcoming C481 mutation-mediated resistance .
PMID: 39025681
9
Clinically, BTK inhibitors have revolutionized treatment of chrX lymphocytic leukemia and other B-cell lymphomas , with newer noncovalent inhibitors like pirtobrutinib overcoming C481 mutation-mediated resistance .
PMID: 36796019
10
BTK inhibition is also being investigated for multiple sclerosis, where BTK expression in microglia and B cells contributes to CNS neuroinflammation , .
PMID: 39578444
11
BTK inhibition is also being investigated for multiple sclerosis, where BTK expression in microglia and B cells contributes to CNS neuroinflammation , .
PMID: 38533819
Disease Associationsβ“˜22
X-linked agammaglobulinemiaOpen Targets
0.85Strong
isolated growth hormone deficiency type IIIOpen Targets
0.73Strong
Non-acquired isolated growth hormone deficiencyOpen Targets
0.73Strong
chronic lymphocytic leukemiaOpen Targets
0.72Strong
Mantle cell lymphomaOpen Targets
0.69Moderate
Bruton-type agammaglobulinemiaOpen Targets
0.69Moderate
non-Hodgkins lymphomaOpen Targets
0.59Moderate
neoplasmOpen Targets
0.58Moderate
Waldenstrom macroglobulinemiaOpen Targets
0.57Moderate
alopecia areataOpen Targets
0.55Moderate
isolated agammaglobulinemiaOpen Targets
0.55Moderate
diffuse large B-cell lymphomaOpen Targets
0.52Moderate
autoimmune thrombocytopenic purpuraOpen Targets
0.51Moderate
common variable immunodeficiencyOpen Targets
0.51Moderate
immunodeficiency diseaseOpen Targets
0.47Moderate
agammaglobulinemiaOpen Targets
0.47Moderate
non-small cell lung carcinomaOpen Targets
0.45Moderate
lymphoplasmacytic lymphomaOpen Targets
0.44Moderate
multiple sclerosisOpen Targets
0.41Moderate
Richter syndromeOpen Targets
0.40Weak
Growth hormone deficiency, isolated, 3, with agammaglobulinemiaUniProt
X-linked agammaglobulinemiaUniProt
Pathogenic Variants346
NM_000061.3(BTK):c.863G>A (p.Arg288Gln)Pathogenic
Autosomal recessive agammaglobulinemia 1|not provided|X-linked agammaglobulinemia with growth hormone deficiency|not specified|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2026β†’ Residue 288
NM_000061.3(BTK):c.423del (p.Lys141fs)Pathogenic
X-linked agammaglobulinemia with growth hormone deficiency|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2026β†’ Residue 141
NM_000061.3(BTK):c.37C>T (p.Arg13Ter)Pathogenic
X-linked agammaglobulinemia|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 13
NM_000061.3(BTK):c.82C>T (p.Arg28Cys)Pathogenic
X-linked agammaglobulinemia with growth hormone deficiency|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2025β†’ Residue 28
NM_000061.3(BTK):c.1558C>T (p.Arg520Ter)Pathogenic
X-linked agammaglobulinemia|not provided|Autosomal recessive agammaglobulinemia 1|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 520
NM_000061.3(BTK):c.1420dup (p.Thr474fs)Pathogenic
X-linked agammaglobulinemia with growth hormone deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 474
NM_000061.3(BTK):c.1574G>A (p.Arg525Gln)Pathogenic
X-linked agammaglobulinemia|Autosomal recessive agammaglobulinemia 1|X-linked agammaglobulinemia with growth hormone deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 525
NM_000061.3(BTK):c.1581_1584del (p.Cys527fs)Pathogenic
Autosomal recessive agammaglobulinemia 1|X-linked agammaglobulinemia with growth hormone deficiency|not provided|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2025β†’ Residue 527
NM_000061.3(BTK):c.1684C>T (p.Arg562Trp)Pathogenic
X-linked agammaglobulinemia|Autosomal recessive agammaglobulinemia 1|X-linked agammaglobulinemia with growth hormone deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 562
NM_000061.3(BTK):c.83G>T (p.Arg28Leu)Pathogenic
X-linked agammaglobulinemia with growth hormone deficiency|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2025β†’ Residue 28
NM_000061.3(BTK):c.1922G>C (p.Arg641Pro)Likely pathogenic
X-linked agammaglobulinemia|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 641
NM_000061.3(BTK):c.894+1G>APathogenic
not provided|X-linked agammaglobulinemia with growth hormone deficiency|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2025
NM_000061.3(BTK):c.763C>T (p.Arg255Ter)Pathogenic
X-linked agammaglobulinemia|Autosomal recessive agammaglobulinemia 1|X-linked agammaglobulinemia with growth hormone deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 255
NM_000061.3(BTK):c.1922G>A (p.Arg641His)Pathogenic
not provided|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 641
NM_000061.3(BTK):c.215dup (p.Asn72fs)Pathogenic
not provided|X-linked agammaglobulinemia|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 72
NM_000061.3(BTK):c.182T>A (p.Ile61Asn)Pathogenic
X-linked agammaglobulinemia with growth hormone deficiency|X-linked agammaglobulinemia
β˜…β˜…β˜†β˜†2025β†’ Residue 61
NM_000061.3(BTK):c.119A>G (p.Tyr40Cys)Pathogenic
not provided|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 40
NM_000061.3(BTK):c.1573C>T (p.Arg525Ter)Pathogenic
not provided|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 525
NM_000061.3(BTK):c.2T>C (p.Met1Thr)Pathogenic
X-linked agammaglobulinemia|X-linked agammaglobulinemia with growth hormone deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_000061.3(BTK):c.215del (p.Asn72fs)Pathogenic
not provided|X-linked agammaglobulinemia with growth hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 72
View on ClinVar β†—
Drug Targets24
ABIVERTINIBPhase III
Tyrosine-protein kinase BTK inhibitor
non-small cell lung carcinoma
ABIVERTINIB MALEATEPhase III
Tyrosine-protein kinase BTK inhibitor
non-small cell lung carcinoma
ACALABRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
chronic lymphocytic leukemia
ACALABRUTINIB MALEATEApproved
Tyrosine-protein kinase BTK inhibitor
chronic lymphocytic leukemia
BMS-986142Phase II
Tyrosine-protein kinase BTK inhibitor
rheumatoid arthritis
BRANEBRUTINIBPhase II
Tyrosine-protein kinase BTK inhibitor
rheumatoid arthritis
EDRALBRUTINIBPhase II
Tyrosine-protein kinase BTK inhibitor
neuromyelitis optica
ELSUBRUTINIBPhase II
Tyrosine-protein kinase BTK inhibitor
rheumatoid arthritis
EVOBRUTINIBPhase III
Tyrosine-protein kinase BTK inhibitor
relapsing-remitting multiple sclerosis
FENEBRUTINIBPhase III
Tyrosine-protein kinase BTK inhibitor
multiple sclerosis
IBRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
chronic lymphocytic leukemia
MSC-2364447Phase I
Tyrosine-protein kinase BTK inhibitor
systemic lupus erythematosus
ORELABRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
neoplasm
PIRTOBRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
Mantle cell lymphoma
POSELTINIBPhase II
Tyrosine-protein kinase BTK inhibitor
rheumatoid arthritis
RILZABRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
autoimmune thrombocytopenic purpura
RITLECITINIBApproved
Tyrosine-protein kinase JAK3 inhibitor
alopecia areata
RITLECITINIB TOSYLATEApproved
Tyrosine-protein kinase JAK3 inhibitor
alopecia areata
SPEBRUTINIBPhase I
Tyrosine-protein kinase BTK inhibitor
Waldenstrom macroglobulinemia
SPEBRUTINIB BESYLATEPhase II
Tyrosine-protein kinase BTK inhibitor
chronic lymphocytic leukemia
TIRABRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
neoplasm
TOLEBRUTINIBPhase III
Tyrosine-protein kinase BTK inhibitor
multiple sclerosis
VECABRUTINIBPhase I/II
Tyrosine-protein kinase BTK inhibitor
B-cell non-Hodgkins lymphoma
ZANUBRUTINIBApproved
Tyrosine-protein kinase BTK inhibitor
Mantle cell lymphoma
Related Genes
GRAP2Protein interaction100%VAV1Protein interaction100%PLCG1Protein interaction100%GRB2Protein interaction100%CD79BProtein interaction100%PIK3R3Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
48%
Heart
6%
Liver
5%
Brain
4%
Ovary
2%
Gene Interaction Network
Click a node to explore
BTKGRAP2VAV1PLCG1GRB2CD79BPIK3R3
PROTEIN STRUCTURE
Preparing viewer…
PDB5P9J Β· 1.08 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.18Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.09 [0.05–0.18]
RankingsWhere BTK stands among ~20K protein-coding genes
  • #810of 20,598
    Most Researched374 Β· top 5%
  • #150of 1,025
    FDA-Approved Drug Targets10 Β· top quartile
  • #168of 5,498
    Most Pathogenic Variants346 Β· top 5%
  • #355of 17,882
    Most Constrained (LOEUF)0.18 Β· top 5%
Genes detectedBTK
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
BTK inhibitors: past, present, and future.
PMID: 39025681
Trends Pharmacol Sci Β· 2024
1.00
2
Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors.
PMID: 35196427
N Engl J Med Β· 2022
0.90
3
Risk-stratification in frontline CLL therapy: standard of care.
PMID: 39644006
Hematology Am Soc Hematol Educ Program Β· 2024
0.80
4
BTK regulates microglial function and neuroinflammation in human stem cell models and mouse models of multiple sclerosis.
PMID: 39578444
Nat Commun Β· 2024
0.70
5
Bruton's tyrosine kinase (BTK) inhibitors for the treatment of primary central nervous system lymphoma (PCNSL): current progress and latest advances.
PMID: 38597202
Leuk Lymphoma Β· 2024
0.64