Alt. symbols: IP3KB | IP3-3KB

Approved name: inositol-trisphosphate 3-kinase B
Alt. names: inositol 1,4,5-trisphosphate 3-kinase B

Location: 1q42.12: 226631690 - 226739323 (-)
Gene type: protein_coding, 3 transcripts.

Scores: LoFtool: 0.123000 | pLI: 0.99885008 | LOEUF: 0.148

HGNC: 6179

NCBI: 3707, RefSeq: .0

Ensembl: ENSG00000143772.11

LRG_ | Status: none

OMIM: 147522

Expression | ProteinAtlas

Inositol 1,4,5-trisphosphate 3-kinase (ITPK) catalyzes the phosphorylation of inositol(1,4,5)trisphosphate (IP3) to inositol(1,3,4,5)tetrakisphosphate (IP4), both of which are modulators of calcium homeostasis. There are 3 ITPK isoforms: ITPKA is expressed solely in neurons, whereas ITPKB and ITPKC are ubiquitous. They share highly homologous kinase domains at their C-termini, but differ in their N-terminal domains, enabling distinct subcellular localization and protein interactions. The activity of these kinases is controlled by both calcium/calmodulin-binding and protein phosphorylation. Recent data has noted essential functions for soluble IP4 in signal transduction pathways contributing to T cell, B cell and neutrophil development and function.

Mareschal et al. (2016) first reported the detection of recurrent somatic ITPKB mutations in diffuse large B-cell lymphoma (DLBCL) (PMID: 26608593). Since then, there have been 3 reports of mono- or bi-allelic germline ITPKB variants in the literature in association with immunological phenotypes. Louis et al. (2016) reported a CVID phenotype in conjunction with ITPKB haploinsufficiency caused by a large contiguous gene deletion in chr1q42.1-42.3 (PMID: 26900472). ITPKB mRNA level was quantified at ~2.4x lower and protein level ~7x lower than controls (PMID: 26900472). Almutairi et al. (2020) then reported a homozygous frameshift variant in ITPKB (c.2583delT; p.Arg862Glufs*4) causing an autosomal recessive T-B+NK+ SCID phenotype in an Egyptian girl. Her phenotype resembled the Itpkb-/- mouse model showing defective thymic development, severe peripheral T-cell lymphopenia, and decreased peripheral B cells (PMID: 14517551). Another mouse model (c.596T>A; p.Cys199Ter) generated through ENU mutagenesis showed similar findings and the authors proposed that severe reduction in the generation of IP4 could prevent sufficient Ras and Erk activation to allow for positive T cell selection (PMID: 15064401). Finally, most recently, Gallo et al. (2020) reported one heterozygous splice-site variant in one patient with elevated IgM levels. [Load More]