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Primary immunodeficiency or monogenic inflammatory bowel disease v9.78 SHARPIN Achchuthan Shanmugasundram Classified gene: SHARPIN as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v9.78 SHARPIN Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated patients and functional evidence including mouse model available in support of the association of SHARPIN gene with autoinflammatory disease. Hence, this gene can be promoted to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.78 SHARPIN Achchuthan Shanmugasundram Gene: sharpin has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v9.77 SHARPIN Achchuthan Shanmugasundram Phenotypes for gene: SHARPIN were changed from Autoinflammation; Immunodeficiency; Recurrent fever; Dermatitis; Recurrent infections to Autoinflammation with episodic fever and immune dysregulation, OMIM:620795; autoinflammation with episodic fever and immune dysregulation, MONDO:0968982
Primary immunodeficiency or monogenic inflammatory bowel disease v9.76 SHARPIN Achchuthan Shanmugasundram Publications for gene: SHARPIN were set to 38609546
Primary immunodeficiency or monogenic inflammatory bowel disease v9.75 SHARPIN Achchuthan Shanmugasundram Tag Q3_26_promote_green tag was added to gene: SHARPIN.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.75 SHARPIN Achchuthan Shanmugasundram reviewed gene: SHARPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17538631, 38609546; Phenotypes: Autoinflammation with episodic fever and immune dysregulation, OMIM:620795, autoinflammation with episodic fever and immune dysregulation, MONDO:0968982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 SHARPIN Boaz Palterer gene: SHARPIN was added
gene: SHARPIN was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature,Expert list
Mode of inheritance for gene: SHARPIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHARPIN were set to 38609546
Phenotypes for gene: SHARPIN were set to Autoinflammation; Immunodeficiency; Recurrent fever; Dermatitis; Recurrent infections
Penetrance for gene: SHARPIN were set to unknown
Added comment: 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