Combined Immunodeficiency

Gene: CHUK

Green List (high evidence)

PMID: 34533979
3 affected individuals from 2 unrelated (but from same region) consanguineous Turkish families, presenting with
recurrent viral/bacterial/fungal infections, absence of secondary lymphoid organs, hypogammaglobulinemia, and limited diversity of T and B cell receptors with evidence of autoreactivity.

WES identified the same homozygous germline missense variant (c.499 G > A, p.G167R) in the CHUK gene (IKKα) in both families. IKKα serves as an essential upstream regulator of the non-canonical NF-κB pathway, which is a critical regulator of immunity, and genetic variations in genes that regulate this pathway can lead to various forms of inborn errors of immunity. The variant segregated with disease with parents as heterozygous carriers. The variant is in the activation segment of the kinase domain and affects the conserved (DF/LG) motif responsible for coordinating magnesium atoms for ATP binding. Supportive immunology assays for the pathway.

Created: 9 Dec 2024, 11:49 p.m. | Last Modified: 9 Dec 2024, 11:49 p.m.

Panel Version: 1.112

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined immunodeficiency, MONDO:0015131, CHUK-related

Publications

• PMID: 34533979

I don't know

PMID 34533979: single individual reported with homozygous missense variant in this gene and recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine. Supportive functional data.
Sources: Literature

Created: 6 Dec 2022, 10:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined immunodeficiency, MONDO:0015131, CHUK-related

Publications

• 34533979