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DLGAP2 – Autism Spectrum Disorder

Evidence from multiple genetic studies suggests that DLGAP2 may play a contributory role in autism spectrum disorder (ASD). A deep exon resequencing study of 515 patients with ASD identified several rare missense variants in DLGAP2, with some variants showing modest association signals when compared with controls (PMID:23915500). In addition, a study focusing on copy number variations in extended ASD pedigrees reported a duplication overlapping DLGAP2 that segregated with the ASD phenotype in three male offspring (PMID:32372567). However, many of the rare missense variants observed were inherited from unaffected parents, and further case‐control analyses have demonstrated only modest enrichment in affected individuals (PMID:27271353). Collectively, these findings place the genetic evidence for DLGAP2 in ASD within a limited spectrum, warranting cautious interpretation in a diagnostic context.

Preliminary functional studies have provided supportive evidence at the molecular level. Reporter gene assays and bioinformatic predictions indicate that non‑coding variants in DLGAP2 can alter gene expression, potentially disrupting synaptic signaling pathways relevant to neurodevelopment (PMID:24416398). Although a precise coding variant with complete HGVS notation was not unequivocally identified, the convergence of genetic and functional data suggests that DLGAP2 merits further investigation as a susceptibility gene for ASD. Key take‑home: While the current evidence supports a limited association, DLGAP2 remains a candidate gene that can refine genetic diagnostic workups once validated by additional studies.

References

  • Molecular autism • 2013 • Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders PMID:23915500
  • American journal of medical genetics. Part B, Neuropsychiatric genetics • 2020 • Segregating patterns of copy number variations in extended autism spectrum disorder pedigrees PMID:32372567
  • Scientific reports • 2016 • Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders PMID:27271353
  • PloS one • 2014 • Role of the DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 in schizophrenia PMID:24416398

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Multiple case reports and multi‑patient studies indicate a potential role for DLGAP2 in ASD; however, the majority of rare variants are inherited from unaffected parents and lack robust segregation (PMID:23915500, PMID:32372567).

Genetic Evidence

Limited

Rare missense variants and CNV events have been identified in ASD cohorts, but the genetic evidence is moderated by low penetrance and inconsistent segregation across families (PMID:27271353).

Functional Evidence

Moderate

Experimental assays, including reporter gene studies, reveal that non‑coding variants in DLGAP2 can alter gene expression, providing a plausible mechanism for synaptic dysregulation in ASD (PMID:24416398).