Inborn errors of human IKAROS: LOF and GOF variants associated with primary immunodeficiency
Open Access
- 26 November 2022
- journal article
- review article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 212 (2), 129-136
- https://doi.org/10.1093/cei/uxac109
Abstract
IKAROS/IKZF1 plays a pivotal role in lymphocyte differentiation and development. Germline mutations in IKZF1, which have been shown to be associated with primary immunodeficiency, can be classified through four different mechanisms of action depending on the protein expression and its functional defects: haploinsufficiency, dimerization defective, dominant negative, and gain of function. These different mechanisms are associated with variable degrees of susceptibility to infectious diseases, autoimmune disorders, allergic diseases, and malignancies. To date, more than 30 heterozygous IKZF1 germline variants have been reported in patients with primary immunodeficiency. Here we review recent discoveries and clinical/immunological characterization of IKAROS-associated diseases that are linked to different mechanisms of action in IKAROS function.Keywords
Funding Information
- Intramural Research Program
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
This publication has 45 references indexed in Scilit:
- Loss of B Cells in Patients with Heterozygous Mutations in IKAROSThe New England Journal of Medicine, 2016
- Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma CellsScience, 2014
- Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the ikaros genePediatric Blood & Cancer, 2011
- Deletion ofIKZF1and Prognosis in Acute Lymphoblastic LeukemiaThe New England Journal of Medicine, 2009
- BCR–ABL1 lymphoblastic leukaemia is characterized by the deletion of IkarosNature, 2008
- Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding ActivitiesOnline Journal of Public Health Informatics, 2000
- Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitorsCurrent Biology, 1998
- Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiationThe EMBO Journal, 1997
- The Ikaros gene encodes a family of functionally diverse zinc finger DNA-binding proteins.Molecular and Cellular Biology, 1994
- Ikaros, an Early Lymphoid-Specific Transcription Factor and a Putative Mediator for T Cell CommitmentScience, 1992