Disorders of immune dysregulation

Gene: PACSIN1

Red List (low evidence)

Single individual reported with de novo missense and functional data.

Created: 26 Dec 2024, 11:43 p.m. | Last Modified: 26 Dec 2024, 11:43 p.m.

Panel Version: 1.0

I don't know

PMID: 36622335
One patient denovo novel missense Q59K, severe infantile SLE, with functional validation
Results: We established that PACSIN1 forms a trimolecular complex with tumor necrosis factor receptor-associated factor 4 (TRAF4) and TRAF6 that is important for the regulation of type I IFN. The Q59K mutation in PACSIN1 augments binding to neural Wiskott-Aldrich syndrome protein while it decreases binding to TRAF4, leading to unrestrained TRAF6-mediated activation of type I IFN. Intriguingly, PACSIN1 Q59K increased TLR-7 but not TLR-9 signaling in human cells, leading to elevated expression of IFNβ and IFN-inducible genes. Untreated SLE patients had high PACSIN1 expression in peripheral blood cells that correlated positively with IFN-related genes. Introduction of the Pacsin1 Q59K mutation into mice caused increased surface TLR-7 and TRAIL expression in B cells
Sources: Literature

Created: 23 Dec 2024, 3:18 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
systemic lupus erythematosis; vasculitis; nephritis

Publications

• 36622335