AlphaFold predicted structure
BTK · Q06187
Mean pLDDT
84.4/ 100
Confident
659 residues
Confidence breakdown
- Very high(≥ 90)51%
- Confident(70–90)35%
- Low(50–70)6%
- Very low(< 50)7%
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AlphaFold (Jumper et al., 2021) · CC BY 4.0
BTK
Chr Xq22.1Bruton tyrosine kinase
- Aliases:
- ATK, XLA, PSCTK1
- MANE:
- ENST00000308731.8
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Agammaglobulinaemia with absent BTK expression
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)COVID-19 research
X-LINKED: hemizygous mutation in males, biallelic mutations in femalesInfantile enterocolitis & monogenic inflammatory bowel disease
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Pituitary hormone deficiency
X-LINKED: hemizygous mutation in males, biallelic mutations in femalesPrimary immunodeficiency or monogenic inflammatory bowel disease
X-LINKED: hemizygous mutation in males, biallelic mutations in femalesGastrointestinal epithelial barrier disorders
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Intellectual disability
X-LINKED: hemizygous mutation in males, biallelic mutations in femalesIUGR and IGF abnormalities
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Disease associations (Open Targets)
X-linked agammaglobulinemia
0.85isolated growth hormone deficiency type III
0.73Non-acquired isolated growth hormone deficiency
0.73B-cell chronic lymphocytic leukemia
0.72Bruton-type agammaglobulinemia
0.70mantle cell lymphoma
0.69isolated agammaglobulinemia
0.69neoplasm
0.59Waldenstrom macroglobulinemia
0.56alopecia areata
0.56
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Tyrosine-protein kinase BTK
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). 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 (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). 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 (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810)
Diseases associated with BTK
Curated MONDO disease pages that list BTK among their top associated genes.