ITPKB

Overview

The ITPKB gene encodes inositol-trisphosphate 3-kinase B, an enzyme involved in the regulation of intracellular calcium levels and PI3K/Akt signaling pathways. Mutations in ITPKB have been linked to various B-cell lymphomas, including DLBCL, PMBCL and, less commonly, FL.¹ ITPKB is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. These mutations are associated with the BN2 genetic subgroup of DLBCL.

Relevance tier by entity

Entity	Tier	Description
DLBCL	1-a	aSHM target and high-confidence DLBCL gene
FL	1-a	aSHM target and high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	6.69
DLBCL	Schmitz cohort	6.81
DLBCL	Reddy cohort	6.71
DLBCL	Chapuy cohort	9.40
FL	GAMBL genomes	3.23

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	0.587	0.000
DLBCL	Yes	Yes	4.294	15.744
FL	Yes	No	6.541	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr1	226864857	226873452	intron	weak_enhancer
chr1	226920563	226927885	TSS	active_promoter
chr1	226921088	226927982	intron-1	enhancer

## ITPKB Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr1	226925148	G>C	Y4*
chr1	226925148	G>T	Y4*

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

1. Mareschal S, Dubois S, Viailly PJ, Bertrand P, Bohers E, Maingonnat C, Jaïs JP, Tesson B, Ruminy P, Peyrouze P, Copie-Bergman C, Fest T, Jo Molina T, Haioun C, Salles G, Tilly H, Lecroq T, Leroy K, Jardin F. Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B-cell lymphoma. Genes Chromosomes Cancer. 2016 Mar;55(3):251-67. doi: 10.1002/gcc.22328. Epub 2015 Nov 26. PMID: 26608593.