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X‐linked agammaglobulinemia (XLA): A genetic tyrosine kinase (Btk) disease
Author(s) -
Mattsson Pekka T.,
Vihinen Mauno,
Smith C. I. Edvard
Publication year - 1996
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.950181009
Subject(s) - bruton's tyrosine kinase , x linked agammaglobulinemia , biology , genetics , mutation , gene , tyrosine kinase , tyrosine , protein kinase domain , signal transduction , biochemistry , mutant
X‐linked agammaglobulinemia is a heritable immunodeficiency disease caused by a differentiation abnormality, resulting in the virtual absence of B Iymphocytes and plasma cells. The affected gene encodes a cytoplasmic protein tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase, designated Btk. Btk and the other family members, Tec, Itk and Bmx, contain five regions, four of which are common structural and functional modules that are found in other signaling proteins. Mutations affect all domains of the gene, but amino acid substitutions seem to be confined to certain regions. More than 150 unique mutations have been identified and are collected in a mutation database, BTKbase. Here we discuss the three‐dimensional structural implications of such mutations and their putative functional role. Of special interest are mutations affecting the pleckstrin homology domain, as Btk is the only disease‐associated protein so far reported to carry mutations in this particular module.