Relevance to Autism

De novo missense variants in AHNAK have been identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014), the Simons Simplex Collection (Iossifov et al., 2014; Turner et al., 2017), and the SPARK cohort (Wang et al., 2020). Single-molecular molecular inversion probe (smMIP) sequencing of 3,363 probands from cohorts with a primary diagnosis of ASD in Wang et al., 2020 identified 15 ASD-associated likely gene-disruptive (LGD) variants and 9 ASD-associated missense variants with CADD scores 30 in the AHNAK gene.

Molecular Function

The protein encoded by this gene is a large (700 kDa) structural scaffold protein consisting of a central domain with 128 aa repeats. The encoded protein may play a role in such diverse processes as blood-brain barrier formation, cell structure and migration, cardiac calcium channel regulation, and tumor metastasis. A much shorter variant encoding a 17 kDa isoform exists for this gene, and the shorter isoform initiates a feedback loop that regulates alternative splicing of this gene.

External Links

References