BTK
Chr XXLRBruton tyrosine kinase
Also known as: AGMX1, AT, ATK, BPK, IGHD3, IMD1, PSCTK1, XLA
This gene encodes a non-receptor tyrosine kinase essential for B-cell development, differentiation, and signaling through the B-cell antigen receptor pathway. Mutations cause X-linked agammaglobulinemia type 1, an immunodeficiency disorder characterized by failure to produce mature B lymphocytes and associated growth hormone deficiency. The gene follows X-linked recessive inheritance and is highly constrained against loss-of-function variants.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 52 | 9 | 64 | 0 | 125 |
Likely Pathogenic | 13 | 34 | 4 | 0 | 51 |
VUS | 5 | 100 | 22 | 1 | 128 |
Likely Benign | 0 | 6 | 90 | 65 | 161 |
Benign | 0 | 1 | 16 | 5 | 22 |
Conflicting | — | 2 | |||
| Total | 70 | 150 | 196 | 71 | 489 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BTK · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Orelabrutinib in Combination with R-CHOP for CD5-positive DLBCL Patients（Rocket Trial）
RECRUITINGIbrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas
ACTIVE NOT RECRUITINGIbrutinib, Fludarabine Phosphate, Cyclophosphamide, and Obinutuzumab in Treating Patients With Chronic Lymphocytic Leukemia
ACTIVE NOT RECRUITINGAcalabrutinib With or Without Obinutuzumab in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
RECRUITINGDeterminants of the Response to BTK Degraders (BTKd) in Double Refractory CLL
RECRUITINGSKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)
RECRUITINGIbrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma
ACTIVE NOT RECRUITINGAS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma
RECRUITINGZanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome
RECRUITINGPrognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia
RECRUITINGLenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
ACTIVE NOT RECRUITINGModified Immune Cells (CD19 CAR T Cells) and Acalabrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
RECRUITINGExternal Resources
Links to major genomics databases and tools