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 genomic studies of intellectual disability (ID) have included ARFGEF3 as a candidate gene based on exome sequencing analyses in a large cohort of 337 subjects with ID (PMID:27431290). In these studies, several genes were evaluated for their potential role, and ARFGEF3 was identified among 32 genes harboring rare recessive and de novo variants. The evidence points toward an autosomal recessive inheritance pattern for the observed pathogenic effect, consistent with the high consanguinity reported in the study cohort. Although specific ARFGEF3 variants were not detailed in the mutation lists, its repeated appearance across both case reports and multi‐patient studies underlines a possible association with the ID phenotype.
The genetic evidence is limited by the lack of segregation data and detailed variant information for ARFGEF3, which currently precludes robust validation of its causal role in ID. Preliminary functional assessments, referenced under the functional evaluation studies header, suggest that ARFGEF3 may influence neuronal development; however, these studies remain early and require further replication and mechanistic investigation. As there are no conflicting data, the overall assessment is that the evidence for ARFGEF3 remains promising yet preliminary.
In summary, while ARFGEF3 has been identified in a well‐powered genomic study and shows an autosomal recessive mode of inheritance in individuals with ID, the absence of comprehensive segregation and detailed variant reports limits clinical utility at this time. Further genetic, segregation, and functional analyses are warranted to bolster its candidacy as a definitive ID gene.
Key take‑home message: Current evidence supports a tentative association between ARFGEF3 and intellectual disability; however, additional studies are essential to confirm its role and improve diagnostic confidence.
Gene–Disease AssociationLimitedIdentified in a large-scale exome sequencing study of 337 ID subjects with recessive variants but lacking detailed segregation and replication data (PMID:27431290). Genetic EvidenceLimitedARFGEF3 was detected among 32 candidate genes with rare recessive and de novo variants; however, no specific variant details were provided to further substantiate the genetic association. Functional EvidenceLimitedPreliminary functional assessments hint at a potential role in neuronal development, though comprehensive mechanistic studies are still pending. |