All missense variants of the NLRP3 gene, listed in Infevers — a comprehensive genetic variant database focused on hereditary autoinflammatory diseases — have undergone testing using the ASC speck assay. This assay is designed to measure the activation of inflammation, which plays a key role in many autoinflammatory conditions.
The results of these tests are now publicly available and easily accessible through the Infevers website. This resource is particularly valuable for researchers, clinicians, and geneticists, offering insights into the functional impact of NLRP3 mutations and contributing to a better understanding of their role in disease mechanisms. By providing detailed data on these variants, Infevers supports ongoing efforts to improve diagnostics, treatments, and patient outcomes in the field of autoinflammatory disorders.

Mechanisms of NLRP3 activation and inhibition elucidated by functional analysis of disease-associated variants
Shouya Feng & al.
Nat Immunol. 2025 Mar;26(3):511-523. doi: 10.1038/s41590-025-02088-9. Epub 2025 Feb 10.

WP1
Eurofever clinical data were integrated into the Human Phenotype Ontology (HPO) to achieve standardized phenotypic coding. Artificial intelligence models were then applied to analyze and refine the dataset. This work represents the first implementation of the HPO framework in the field of autoinflammatory diseases, improving data accuracy and interpretability.

WP2
Patient enrollment has been completed, including 69 PBMC and 164 DNA samples. Genotyping using the GSA array was performed on 160 samples. Polygenic Risk Score (PRS), epigenomic, and NEATseq studies are ongoing. A novel severity score for Adenosine Deaminase 2 Deficiency (DADA2) was developed and is currently being validated using real-world data from the Eurofever registry.

WP3
Preliminary analyses of NLRP1 variants have been completed, and optimization work for PSTPIP1 and NLRC4 is in progress.