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SH2D6 – Autism Spectrum Disorder

The gene SH2D6 (HGNC:30439) has been implicated in autism spectrum disorder (MONDO_0005258) based on copy number variants discovered in patients from consanguineous families. In one case report, a homozygous 2p11.2 deletion affecting multiple genes was identified in a boy presenting with ASD, intellectual disability, and hearing impairment (PMID:30284680). In addition, multi‐patient studies have detected a chimeric ELMOD3-SH2D6 fusion transcript in four unrelated ASD families (PMID:31800155), supporting an autosomal recessive mode of inheritance in this context.

Despite these findings, the evidence for a direct causative role for SH2D6 in ASD remains limited because the reported copy number variants overlap neighboring genes such as ELMOD3 and CAPG, and segregation data is minimal. Functional assessments have been confined to the demonstration of elevated fusion transcript expression without direct interrogation of SH2D6’s individual contribution. Key take‑home: While preliminary genetic findings hint at a potential role for SH2D6 in autism spectrum disorder, further targeted studies are required to clarify its pathogenic impact for robust clinical decision‑making.

References

  • Journal of applied genetics • 2019 • Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology PMID:30284680
  • Journal of cellular and molecular medicine • 2020 • ELMOD3-SH2D6 gene fusion as a possible co‑star actor in autism spectrum disorder scenario PMID:31800155

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Evidence is based on a single case report (1 proband [PMID:30284680]) and a study of four unrelated ASD families with a chimeric ELMOD3-SH2D6 transcript ([PMID:31800155]), with confounding deletions that include neighboring genes.

Genetic Evidence

Limited

Genetic data are limited to copy number variants affecting a genomic region that encompasses SH2D6, without independent single nucleotide variants, and minimal segregation information.

Functional Evidence

Limited

Functional studies are restricted to the detection of an ELMOD3-SH2D6 fusion transcript with increased expression, lacking direct functional assays specific to SH2D6.