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AP1S2 – Autism Spectrum Disorder

AP1S2 has been nominated as an Autism Spectrum Disorder risk gene based on X chromosome–wide common variant association studies. In two cohorts comprising 6,873 ASD cases and 8,981 controls, 59 X-linked SNPs surpassed Bonferroni correction (p-values 7.9×10⁻⁶ to 1.51×10⁻⁵), mapping 91 genes within 10 kb of these loci; AP1S2 was one of 17 genes implicated (59 SNPs [PMID:39108515]; gene mapping [PMID:39706197]). No rare variant burden or family segregation data in ASD have been reported, and there are no functional assays directly linking AP1S2 perturbation to ASD phenotypes. Given the absence of replication in independent rare‐variant studies or mechanistic validation in neuronal models, the current evidence places AP1S2 in a limited association category. Key Take-home: AP1S2 shows limited common‐variant association with ASD risk; further rare‐variant and functional studies are required to substantiate clinical relevance.

References

  • medRxiv : the preprint server for health sciences • 2024 • Chromosome X-Wide Common Variant Association Study (XWAS) in Autism Spectrum Disorder. PMID:39108515
  • American Journal of Human Genetics • 2025 • Chromosome X-wide common variant association study in autism spectrum disorder. PMID:39706197

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Association of AP1S2 from two XWAS cohorts (6,873 ASD cases vs. 8,981 controls) with one common‐variant locus within 10 kb (PMID:39108515; PMID:39706197); no rare‐variant, segregation, or functional validation in ASD.

Genetic Evidence

Limited

Single common variant association implicating AP1S2 from XWAS; absence of Mendelian segregation or rare variant burden data.

Functional Evidence

None

No ASD‐specific functional studies of AP1S2 reported.