Disrupted Ca²⁺ homeostasis and immunodeficiency in patients with functional IP₃ receptor subtype 3 defects.

ABSTRACT: Calcium signaling is essential for lymphocyte activation, with genetic disruptions of store-operated calcium (Ca²⁺) entry resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP₃R), a homo- or heterotetramer of the IP₃R1-3 isoforms, amplifies lymphocyte signaling by releasing Ca²⁺ from endoplasmic reticulum stores following antigen stimulation. Although knockout of all IP₃R isoforms in mice causes immunodeficiency, the seeming redundancy of the isoforms is thought to explain the absence of variants in human immunodeficiency. In this study, we identified compound heterozygous variants of ITPR3 (a gene encoding IP₃R subtype 3) in two unrelated Caucasian patients presenting with immunodeficiency. To

SUBMITTER: Neumann J 

PROVIDER: S-EPMC9794825 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature