Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SHARPIN

Oda et al. described 1 patient from 1 kindred, harboring biallelic loss-of-function mutations in the SHARPIN gene. They presented with distinct clinical autoinflammatory features, recurrent fevers, and subtle immunodeficiency. The underlying mechanism was validated ex vivo using patient-derived cells, demonstrating that the absence of SHARPIN severely destabilizes the linear ubiquitin chain assembly complex (LUBAC), resulting in impaired NF-κB signaling, defective linear ubiquitination, and dysregulated TNF-mediated cell death. The phenotype and mechanism were further validated using in vivo animal models; complete knockout Sharpin-deficient mice (Sharpin cpdm) successfully recreated the severe chronic proliferative dermatitis and multi-organ autoinflammation, confirming the gene's critical role in maintaining immune homeostasis and preventing aberrant cell death.
Sources: Literature, Expert list

Created: 17 Jun 2026, 4:28 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Autoinflammation; Immunodeficiency; Recurrent fever; Dermatitis; Recurrent infections

Publications

• 38609546