AVIL – Multiple Sclerosis

AVIL (HGNC:14188) has been evaluated as a candidate gene in studies investigating the vitamin D signaling pathway in families affected by multiple sclerosis (PMID:30900415). In a whole‑exome sequencing study of 15 families with at least two affected individuals each (PMID:30900415), exonic variants were identified in multiple candidate genes. Among these, the AVIL variant c.610A>G (p.Lys204Glu) was reported; however, its segregation with disease was not robust, as the frequency and distribution between affected and unaffected family members did not differ significantly. This lack of clear variant enrichment limits the current genetic evidence, and the inheritance pattern remains complex, with no clear Mendelian model established.

A separate study using a large case‑control cohort (2876 MS patients versus 2910 controls; PMID:23160276) provided functional insights by identifying a regulatory variant (rs10877013) that exhibits allele‑dependent enhancer activity. Functional assays demonstrated that this variant can alter the expression of several genes in the locus, including AVIL, thereby offering moderate experimental support for a role in the pathogenesis of MS. However, since these findings are derived from a locus‑wide association rather than a gene‑specific mutational burden, the overall clinical validity of AVIL in multiple sclerosis remains limited. Key take‑home: Although functional studies suggest a potential regulatory role for AVIL, current genetic evidence is insufficient to support its use as a standalone diagnostic marker for multiple sclerosis.

References

• Brain and behavior • 2019 • Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‑exome next generation sequencing PMID:30900415
• Journal of medical genetics • 2013 • Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis PMID:23160276

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