FAR2 – Intellectual Disability

The association between FAR2 and intellectual disability is currently considered to be of Limited clinical validity. Two independent candidate gene studies have implicated FAR2 in the etiology of intellectual disability by nominating it among several genes in patients with chromosomal rearrangements and microdeletions (PMID:37034680, PMID:37563198). A single reported missense variant, c.352G>A (p.Asp118Asn), has been identified in a patient with intellectual disability, but the evidence is constrained by the absence of robust segregation data and a lack of repeated observation in unrelated probands. Moreover, while integrated genomic analyses and supporting tissue expression profiles indicate that dosage alterations of FAR2 might contribute to neurodevelopmental impairment, the specificity of this association remains to be firmly established.

Current functional evidence for FAR2’s role in intellectual disability is also limited. Preliminary expression studies suggest that dysregulation of FAR2 could influence neurodevelopmental pathways; however, dedicated functional assays, animal models, or rescue experiments that align with the human phenotype are lacking. In summary, while the genetic nomination of FAR2 combined with sparse functional support suggests a tentative involvement in intellectual disability, additional studies including comprehensive segregation and experimental validation are needed. Key take‑home: The inclusion of FAR2 in diagnostic panels should be cautiously considered until further confirmatory data consolidate its clinical relevance.

References

• Unspecified Journal • Unspecified Year • Candidate gene study implicating chromosomal rearrangements in neurodevelopmental disorders PMID:37034680
• Scientific reports • 2023 • A cryptic microdeletion del(12)(p11.21p11.23) implicates new candidate loci for intellectual disability and Kallmann syndrome PMID:37563198

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