BLNK Gene

The BLNK gene (BLNK stands for "B Cell Linker") is a protein-coding gene localized on chromosome 10: 96.19 - 96.27. The BLNK gene encodes the B cell linker protein, an adaptor protein also known as SLP-65, BASH or BCA (see also under Linker). Alternatively spliced transcript variants have been found for this gene.

BLNK is expressed in B cells and macrophages and plays a major role in B cell receptor signaling, analogous to the role its paralog SLP-76 plays in T cell receptor signaling. In the absence of known intrinsic enzymatic activity, the function of the protein encoded by BLNK is to temporally and spatially coordinate and regulate signaling effectors downstream of the B-cell receptor.

Mutations in this gene cause disease with hypoglobulinemia and absent B cells because the transition from pro- to pre-B cells is blocked during development. Deficiency of this protein has also been demonstrated in some cases of acute B lymphoblastic leukemia.

Diseases associated with BLNK include:

Agammaglobulinemia 4 (autosomal recessive) mutation in BLNK.

Minegishi et al identified a homozygous splicing defect in the BLNK gene (604515.0001). The patient's mother and father, who were heterozygous for the mutation, were healthy and had normal concentrations of serum immunoglobulins and normal numbers of B cells. The results suggest that BLNK plays a critical role in orchestrating the transition from pro-B cells to pre-B cells.

The encoded linker protein functions as a central linker protein downstream of the B cell receptor (BCR) and links the SYK kinase to a variety of signaling pathways, thereby regulating the biological outcomes of B cell function and development. The linker protein plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. It is important for NF-kappa-B and NFAT activation, and plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization. It is required for BCR trafficking to late endosomes. It may play an important role in BCR-induced B cell apoptosis. In knockout mice, BLNK deficiency leads to partial blockage of B cell development. In humans, BLNK deficiency leads to much more profound blockage of B cell development.

1. Minegishi Yet al. (1999) An essential role for BLNK in human B cell development. Science 286: 1954-1957.