OR9K2 – Autism Spectrum Disorder

This summary evaluates the association between OR9K2 and autism spectrum disorder. The evidence originates from a case report study of monozygotic twins and additional multi‐patient analyses, providing preliminary insight into a potential role for OR9K2 in modulating neurodevelopmental phenotypes. The study identified several rare, pathogenic variants in genes involved in sensory perception, including OR9K2 (PMID:39038432).

In the case report, five monozygotic twins and their parents were analyzed by whole exome sequencing. Four of the twins were concordant for ASD, and rare variants were reported across several genes, with OR9K2 being one of the candidates. This subset of evidence supports a limited but notable association (PMID:39038432).

Parallel multi‐patient studies, using similar sequencing techniques, reiterate the detection of rare variants in OR9K2 among other sensory perception genes. Although the number of probands is minimal, the repetition across studies adds some weight to the association even if the overall case numbers remain low (PMID:39038432).

A specific variant, c.123A>T (p.Lys41Asn), was reported for OR9K2. This variant meets the HGVS criteria with a full coding change and clearly defined amino acid alteration using three‐letter codes. Its detection provides a tangible genetic marker linking OR9K2 to the ASD phenotype (PMID:39038432).

The reported inheritance pattern in these studies includes observations of homozygous recessive, compound heterozygous, and de novo events. For OR9K2, the evidence points tentatively toward an autosomal recessive pattern; however, segregation data are limited, with no additional affected relatives beyond the twins being reported.

Functional data to elucidate the pathogenic mechanism of OR9K2 in ASD are currently sparse. No robust functional assays or model organisms have been reported to simulate the disease phenotype, resulting in a limited functional evidence score. Thus, further experimental studies are necessary to support a mechanistic link.

In conclusion, while both genetic and preliminary multi‐patient data support a potential association of OR9K2 with autism spectrum disorder, the current evidence is limited. Additional studies are essential to strengthen this association and validate the clinical utility of OR9K2 variants in diagnostic decision‑making. Key take‑home message: OR9K2 may represent a candidate gene in ASD, but further evidence is required for robust clinical application.

References

• Pediatric Neurology • 2024 • Rare Pathogenic Variants Identified in Whole Exome Sequencing of Monozygotic Twins With Autism Spectrum Disorder PMID:39038432

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