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BTK Bruton tyrosine kinase [ Homo sapiens (human) ]

Gene ID: 695, updated on 2-Mar-2021

Summary

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Official Symbol
BTKprovided by HGNC
Official Full Name
Bruton tyrosine kinaseprovided by HGNC
Primary source
HGNC:HGNC:1133
See related
Ensembl:ENSG00000010671 MIM:300300
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AT; ATK; BPK; XLA; IMD1; AGMX1; IGHD3; PSCTK1
Summary
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. [provided by RefSeq, Dec 2013]
Expression
Biased expression in lymph node (RPKM 25.2), spleen (RPKM 18.4) and 13 other tissues See more
Orthologs
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Genomic context

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See BTK in Genome Data Viewer
Location:
Xq22.1
Exon count:
21
Annotation release Status Assembly Chr Location
109.20210226 current GRCh38.p13 (GCF_000001405.39) X NC_000023.11 (101349450..101390796, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (100604438..100645784, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein L21 pseudogene 132 Neighboring gene translocase of inner mitochondrial membrane 8A Neighboring gene RPL36A-HNRNPH2 readthrough Neighboring gene ribosomal protein L36a Neighboring gene galactosidase alpha

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton's tyrosine kinase (BTK) gene mutations. Gao S, et al. BMC Med Genet, 2020 Jun 17. PMID 32552675, Free PMC Article
  2. Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases. Amatya N, et al. Proc Natl Acad Sci U S A, 2019 Oct 22. PMID 31591208, Free PMC Article
  3. Noncovalent inhibitors reveal BTK gatekeeper and auto-inhibitory residues that control its transforming activity. Wang S, et al. JCI Insight, 2019 Jun 20. PMID 31217352, Free PMC Article
  4. A novel Bruton tyrosine kinase gene variation was found in an adult with X-linked agammaglobulinemia during blood cross-matching prior to surgical operation. Wang N, et al. Transfus Med, 2019 Oct. PMID 31115091
  5. Structural mechanism for Bruton's tyrosine kinase activation at the cell membrane. Wang Q, et al. Proc Natl Acad Sci U S A, 2019 May 7. PMID 31019091, Free PMC Article

See all (320) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations.
    Title: Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations.
  2. Bruton's tyrosine kinase inhibition effectively protects against human IgE-mediated anaphylaxis.
    Title: Bruton's tyrosine kinase inhibition effectively protects against human IgE-mediated anaphylaxis.
  3. Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1beta-mediated colitis.
    Title: Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β-mediated colitis.
  4. Noncatalytic Bruton's tyrosine kinase activates PLCgamma2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells.
    Title: Noncatalytic Bruton's tyrosine kinase activates PLCγ<sub>2</sub> variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells.
  5. Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton's tyrosine kinase (BTK) gene mutations.
    Title: Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton's tyrosine kinase (BTK) gene mutations.
  6. Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies.
    Title: Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies.
  7. Noncovalent inhibitors reveal BTK gatekeeper and auto-inhibitory residues that control its transforming activity.
    Title: Noncovalent inhibitors reveal BTK gatekeeper and auto-inhibitory residues that control its transforming activity.
  8. Bruton's tyrosine kinase associates and phosphorylates IkappaBalpha at Y289 and Y305, promoting NF-kappaB activation.
    Title: Activation of NF-κB in B cell receptor signaling through Bruton's tyrosine kinase-dependent phosphorylation of IκB-α.
  9. ROR1/CD19 complex effectively substitutes for BCR-BTK signaling to promote activation and growth of mantle cell lymphoma cells
    Title: Cutting Edge: ROR1/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell Receptor-BTK Signaling Pathway.
  10. In the resting state, the BTK PH domain binds to the activation loop face of the kinase domain and allosterically alters key sites within the kinase domain.
    Title: Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases.
Submit: New GeneRIF Correction See all GeneRIFs (161)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
X-linked agammaglobulinemia
MedGen: C0221026 OMIM: 300755 GeneReviews: X-Linked Agammaglobulinemia
Compare labs
X-linked agammaglobulinemia with growth hormone deficiency
MedGen: C0472813 OMIM: 307200 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2012-05-17)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2012-05-17)

ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Nef nef A cell-based bimolecular fluorescence complementation assay demonstrates that HIV-1 Nef interacts with the Tec family members Bmx, Btk, and Itk, but not with Tec or Txk in 293T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC126261, MGC126262

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding TAS
Traceable Author Statement
more info
 PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
  
non-membrane spanning protein tyrosine kinase activity TAS
Traceable Author Statement
more info
 PubMed 
phosphatidylinositol-3,4,5-trisphosphate binding IDA
Inferred from Direct Assay
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein tyrosine kinase activity EXP
Inferred from Experiment
more info
 PubMed 
protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
protein tyrosine kinase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
B cell activation TAS
Traceable Author Statement
more info
 PubMed 
B cell affinity maturation IEA
Inferred from Electronic Annotation
more info
  
B cell receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
  
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
  
I-kappaB kinase/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
  
MyD88-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
  
adaptive immune response TAS
Traceable Author Statement
more info
 PubMed 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
calcium-mediated signaling TAS
Traceable Author Statement
more info
 PubMed 
cell maturation IEA
Inferred from Electronic Annotation
more info
  
cellular response to interleukin-7 IEA
Inferred from Electronic Annotation
more info
  
cellular response to molecule of fungal origin IEA
Inferred from Electronic Annotation
more info
  
cellular response to reactive oxygen species IEA
Inferred from Electronic Annotation
more info
  
histamine secretion by mast cell IEA
Inferred from Electronic Annotation
more info
  
innate immune response TAS
Traceable Author Statement
more info
 PubMed 
intracellular signal transduction TAS
Traceable Author Statement
more info
 PubMed 
mesoderm development TAS
Traceable Author Statement
more info
 PubMed 
negative regulation of B cell proliferation IEA
Inferred from Electronic Annotation
more info
  
negative regulation of cytokine production IEA
Inferred from Electronic Annotation
more info
  
peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of B cell differentiation TAS
Traceable Author Statement
more info
 PubMed 
positive regulation of NF-kappaB transcription factor activity TAS
Traceable Author Statement
more info
 PubMed 
positive regulation of type I hypersensitivity IEA
Inferred from Electronic Annotation
more info
  
positive regulation of type III hypersensitivity IEA
Inferred from Electronic Annotation
more info
  
protein autophosphorylation IEA
Inferred from Electronic Annotation
more info
  
protein phosphorylation TAS
Traceable Author Statement
more info
 PubMed 
regulation of B cell apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
regulation of B cell cytokine production TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
cytoplasmic vesicle IEA
Inferred from Electronic Annotation
more info
  
cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
cytosol TAS
Traceable Author Statement
more info
 PubMed 
membrane raft IDA
Inferred from Direct Assay
more info
 PubMed 
nucleus TAS
Traceable Author Statement
more info
 PubMed 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
tyrosine-protein kinase BTK
Names
B-cell progenitor kinase
Bruton agammaglobulinemia tyrosine kinase
Bruton's tyrosine kinase
agammaglobulinaemia tyrosine kinase
dominant-negative kinase-deficient Brutons tyrosine kinase
truncated Bruton agammaglobulinemia tyrosine kinase
NP_000052.1
NP_001274273.1
NP_001274274.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009616.1 RefSeqGene

    Range
    429..41778
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_128

mRNA and Protein(s)

  1. NM_000061.3 → NP_000052.1  tyrosine-protein kinase BTK isoform 1

    See identical proteins and their annotated locations for NP_000052.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AK057105, BC109079, DA619542, DB636737
    Consensus CDS
    CCDS14482.1
    UniProtKB/Swiss-Prot
    Q06187
    UniProtKB/TrEMBL
    Q5JY90
    Related
    ENSP00000308176.7, ENST00000308731.7
    Conserved Domains (4) summary
    cd05113
    Location:397 → 652
    PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome
    cd10397
    Location:274 → 379
    SH2_Tec_Btk; Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk)
    cd11906
    Location:217 → 271
    SH3_BTK; Src Homology 3 domain of Bruton's tyrosine kinase
    cd01238
    Location:6 → 166
    PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain

  2. NM_001287344.2 → NP_001274273.1  tyrosine-protein kinase BTK isoform 3

    See identical proteins and their annotated locations for NP_001274273.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and CDS, and represents the use of an alternate promoter, compared to variant 1. The resulting protein (isoform 3) has a longer N-terminus, compared to isoform 1.
    Source sequence(s)
    AK309851, AV733045, DB331677, DB636737
    Consensus CDS
    CCDS76003.1
    UniProtKB/Swiss-Prot
    Q06187
    Related
    ENSP00000483570.1, ENST00000621635.4
    Conserved Domains (6) summary
    cd05113
    Location:431 → 686
    PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome
    cd10397
    Location:308 → 413
    SH2_Tec_Btk; Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk)
    cd11906
    Location:251 → 305
    SH3_BTK; Src Homology 3 domain of Bruton's tyrosine kinase
    cd01238
    Location:40 → 200
    PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain
    pfam00169
    Location:38 → 167
    PH; PH domain
    pfam07714
    Location:436 → 685
    Pkinase_Tyr; Protein tyrosine kinase

  3. NM_001287345.2 → NP_001274274.1  tyrosine-protein kinase BTK isoform 2

    See identical proteins and their annotated locations for NP_001274274.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate exon in the 5' UTR and lacks several exons in the 3' CDS compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.
    Source sequence(s)
    AK057105, AL035422, AU107296, BC109079, DA619542
    Consensus CDS
    CCDS76002.1
    UniProtKB/Swiss-Prot
    Q06187
    UniProtKB/TrEMBL
    Q5JY90
    Related
    ENSP00000361971.1, ENST00000372880.5
    Conserved Domains (4) summary
    cd11906
    Location:217 → 271
    SH3_BTK; Src Homology 3 domain of Bruton's tyrosine kinase
    cd01238
    Location:6 → 166
    PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain
    cl15255
    Location:274 → 350
    SH2; Src homology 2 (SH2) domain
    cl21453
    Location:346 → 476
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210226

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p13 Primary Assembly

    Range
    101349450..101390796 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q06187.3 GenPept UniProtKB/Swiss-Prot:Q06187

Gene LinkOut

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