Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
Recent cross‐phenotype genome‑wide association studies (GWAS) have identified a robust genetic correlation between systemic sclerosis and other autoimmune disorders, leading to the prioritization of several candidate genes, including CFAP263 (PMID:39676709) (PMID:39006426). These studies analyzed large cohorts and detected 44 significant non‐HLA loci, with integrative analyses narrowing the causal candidates to nine loci that shared causal variants among patients with systemic sclerosis and primary biliary cholangitis. Although the focus was on overall shared genetic susceptibility, CFAP263 emerged as a notable candidate based on comprehensive Bayesian colocalization and pathway enrichment analyses.
The genetic evidence for CFAP263 is supported by strong association statistics. In one study, the global genetic correlation was reported at 0.84 with a significance of p = 1.7 × 10^-6 (PMID:39676709), while a second independent analysis provided concordant colocalization evidence (PMID:39006426). These findings indicate that CFAP263 may play a role in the complex genetic architecture underlying systemic sclerosis, even as the direct causative variants remain to be clarified.
The genetic architecture appears to be complex, as no single variant has been isolated in a Mendelian pattern. Instead, CFAP263 was identified through statistical association in a multifactorial context. Although a specific coding variant with a complete HGVS annotation was not reported in the available studies, the overall gene-based signal contributes to the disease risk profile. This supports a model in which common variants and regulatory effects cumulatively influence susceptibility.
Functional evidence for CFAP263 in the pathogenesis of systemic sclerosis is currently limited. Preliminary studies hint at its potential involvement in immune regulatory pathways, but direct experimental validations such as knock‑out models, expression analyses, or rescue experiments have yet to be published. This lack of extensive functional validation underscores the need for further investigation to understand the mechanistic basis of the association.
In summary, the convergence of statistical genetics from two independent large-scale GWAS meta‑analyses provides strong evidence for the association between CFAP263 and systemic sclerosis. While genetic data robustly support the association, functional assessments remain in early stages, warranting further experimental exploration to validate the causal role and underlying mechanism. This integrated evidence supports the use of CFAP263 as a candidate marker in diagnostic decision‑making and targeted commercial applications.
Key take‑home: The identification of CFAP263 through rigorous cross‑phenotype analyses establishes it as a promising genetic contributor to systemic sclerosis, meriting further investigation for clinical and therapeutic utility.
Gene–Disease AssociationStrongAssociation supported by two independent cross‑phenotype GWAS meta‑analyses identifying 44 significant loci with CFAP263 prioritized among nine loci showing shared causal variants (PMID:39676709) (PMID:39006426). Genetic EvidenceStrongRobust statistical evidence from large cohorts shows a high global genetic correlation (rg = 0.84, p = 1.7 × 10^-6) and concordant colocalization analyses supporting CFAP263’s involvement (PMID:39676709) (PMID:39006426). Functional EvidenceLimitedPreliminary functional data suggest possible immune regulatory roles for CFAP263; however, detailed experimental validations such as expression studies, animal models, or rescue experiments are currently lacking. |