Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: IKBKE

Red List (low evidence)

IKBKE encodes IKKε (Inhibitor of nuclear factor kappa-B kinase subunit epsilon), a noncanonical IκB kinase that plays a nonredundant role in mediating the innate immune response to viral infections.

Reyahi et al. identified a monoallelic truncating variant in IKBKE (c.312delC) as the cause of highly disabling, recurrent Herpes Simplex Virus type 2 (HSV-2) meningitis. Functional analyses demonstrate that this mutated allele encodes a truncated protein lacking kinase activity, which exerts a dominant-negative effect over the wild-type protein. This results in a functional deficiency within the cGAS/STING pathway, impaired STING phosphorylation, and a failure of patient cells (including stem cell-derived microglia) to mount an adequate IFN-β antiviral response against HSV-2 and double-stranded DNA.
Sources: Literature

Created: 17 Jun 2026, 3:40 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Herpes Simplex Virus type 2 (HSV-2) meningitis; Mollaret meningitis

Publications

• 37937644