BTK Gene: Bruton Tyrosine Kinase - Function, Mutations, and Associated Diseases
Comprehensive biomedical overview of the BTK gene, including genomic context, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | BTK |
|---|---|
| Full Name | Bruton tyrosine kinase |
| Gene Type | Protein coding |
| Chromosomal Location | Xq22.1 |
| NCBI Gene ID | 695 ncbi.nlm.nih.gov/gene/695 |
| Ensembl ID | ENSG00000010671 |
| UniProt ID | Q06187 |
| OMIM ID | 300300 |
| HGNC ID | 1133 |
| Aliases | AGMX1, ATK, BPK, IMD1, PSCTK1, XLA |
Description
The BTK gene encodes Bruton tyrosine kinase, a non-receptor tyrosine kinase essential for B-cell development and function. It plays a critical role in B-cell receptor (BCR) signaling, regulating B-cell survival, proliferation, and differentiation. Mutations in BTK cause X-linked agammaglobulinemia (XLA), a primary immunodeficiency characterized by a lack of mature B cells and low immunoglobulin levels. BTK is also a therapeutic target in B-cell malignancies, with inhibitors like ibrutinib used in clinical practice.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked agammaglobulinemia (XLA) | Loss-of-function mutations in BTK disrupt BCR signaling, leading to a block in B-cell development at the pre-B cell stage, resulting in absent or severely reduced mature B cells and immunoglobulins. | OMIM 300300; ClinVar; PMID: 1566100 (Vetrie et al., 1993) |
| Chronic lymphocytic leukemia (CLL) | BTK is constitutively active in CLL cells, promoting survival and proliferation. BTK inhibitors (e.g., ibrutinib) are effective in treating CLL. | COSMIC; PMID: 23563236 (Byrd et al., 2013) |
| Waldenström macroglobulinemia | Somatic mutations in BTK (e.g., C481S) confer resistance to ibrutinib, but BTK is a key driver in this disease. | COSMIC; PMID: 23160464 (Treon et al., 2012) |
| Rheumatoid arthritis (RA) | BTK is involved in inflammatory signaling pathways; BTK inhibitors are being explored as therapeutic agents for autoimmune diseases. | PMID: 25231985 (Di Paolo et al., 2011) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | High (nTPM ~ 50) | High expression in B-cell precursors |
| Spleen | High (nTPM ~ 40) | High in B-cell zones |
| Lymph node | High (nTPM ~ 35) | High in B-cell areas |
| Blood | Moderate (nTPM ~ 20) | Expressed in B cells and some myeloid cells |
| Lung | Low (nTPM ~ 5) | Low expression |
| Liver | Low (nTPM ~ 3) | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Ramos (Burkitt lymphoma) | High (nTPM ~ 80) | B-cell line, high BTK expression |
| Daudi (Burkitt lymphoma) | High (nTPM ~ 70) | B-cell line |
| Jurkat (T-cell leukemia) | Low (nTPM ~ 10) | T-cell line, low expression |
| K562 (CML) | Low (nTPM ~ 5) | Myeloid line, low expression |
| HeLa (cervical carcinoma) | Low (nTPM ~ 2) | Epithelial line, minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.82C>T (p.Arg28Ter) | Nonsense | ~5% of XLA cases | Premature stop codon, loss of function |
| c.2038C>T (p.Arg680Cys) | Missense | ~2% of XLA cases | Disrupts kinase domain, loss of function |
| c.1880T>C (p.Leu627Pro) | Missense | Rare | Affects SH2 domain, impairs signaling |
| c.1630C>T (p.Arg544Cys) | Missense | ~3% of XLA cases | In SH2 domain, reduces activity |
| c.1843T>C (p.Cys481Arg) | Missense | Somatic in CLL (resistance) | Gain-of-function? Actually confers resistance to ibrutinib, but not gain-of-function; it alters drug binding |
Mutation functional classification
Loss of Function (LOF)
Most BTK mutations in XLA are loss-of-function, leading to reduced or absent kinase activity, impaired BCR signaling, and defective B-cell development.
Gain of Function (GOF)
Somatic mutations like C481S in CLL are not gain-of-function but confer resistance to BTK inhibitors; however, some activating mutations have been reported in rare lymphomas, but not well-documented.
Dominant Negative (DN)
Not typically described for BTK; XLA is recessive, and BTK is on the X chromosome, so males are hemizygous.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine kinase activity | • ATP binding |
| • signal transduction | • B cell receptor signaling pathway |
| • cell proliferation | • apoptotic process |
| • immune response | • phosphorylation |
Pathways
• B cell receptor signaling pathway
• Fc receptor signaling pathway
• Toll-like receptor signaling pathway
• Chemokine signaling pathway
• PI3K-Akt signaling pathway
• NF-kappaB signaling pathway
Protein Summary
Bruton tyrosine kinase (BTK) is a 659-amino acid protein with a molecular weight of ~76 kDa. It contains PH, SH2, SH3, and kinase domains. BTK is activated by SRC family kinases upon BCR engagement, leading to phosphorylation of PLCγ2 and downstream calcium mobilization, NF-κB activation, and cell survival. BTK is predominantly expressed in B cells and is critical for B-cell maturation. Mutations in BTK cause XLA, and BTK inhibitors are used in treating B-cell malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IBTK Knockout HEK293 Cell Line | EDJ-KQ8345 | Human | 25998 | Details Get a Quote |
| BTK Knockout HEK293 Cell Line | EDJ-KQ17805 | Human | 695 | Details Get a Quote |
| IBTK Knockout HeLa Cell Line | EDJ-KQ33029 | Human | 25998 | Details Get a Quote |
| IBTK Knockout A-549 Cell Line | EDJ-KQ34361 | Human | 25998 | Details Get a Quote |
| IBTK Knockout HCT 116 Cell Line | EDJ-KQ34362 | Human | 25998 | Details Get a Quote |
| BTK Knockout U-2932 Cell Line | EDJ-KZ122 | Human | 695 | Details Get a Quote |
| BTK Knockout HeLa Cell Line | EDJ-KQ52737 | Human | 695 | Details Get a Quote |
| BTK Knockout A-549 Cell Line | EDJ-KQ61208 | Human | 695 | Details Get a Quote |
| BTK Knockout HCT 116 Cell Line | EDJ-KQ69701 | Human | 695 | Details Get a Quote |
| BTK (p.C633=) Point Mutation in HAP1 Cell Line | EDC03422 | Human | 695 | Details Get a Quote |
| BTK (p.P80S) Point Mutation in HAP1 Cell Line | EDC03423 | Human | 695 | Details Get a Quote |
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