The AKAP6 gene encodes a protein belonging to the A-Kinase Anchor Proteins (AKAPs) family. Members of this family are responsible for binding to the regulatory subunit of the holoenzyme Protein Kinase A (PKA) and anchoring it to the nuclear membrane or sarcoplasmic reticulum. AKAP6 is responsible for maintaining a cAMP-responsive signaling complex consisting of PKA, PDE4D3 and EPAC1. Through this complex, the AKAP6 protein coordinates two coupled cAMP dependent loops. The protein is also believed to play a role in the positive regulation of cell growth, particularly in cardiac muscle cell development.
The AKAP6 gene is located on the long arm of chromosome 14. It spans a length of 508.4 kb of DNA and its coding sequence is contained within 20 exons. The gene encodes a 256.7 kDa protein product comprising 2319 amino acids. An additional 120 kDa isoform of the AKAP6 protein exists due to an alternatively spliced transcript variant. The gene is found to be overexpressed in cardiac and skeletal muscle and several regions of the brain.
Monies et al. (2017) described the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 3-year-old female from a consanguineous family, presented with intellectual disability and precocious puberty. Reflex WES helped identify a novel heterozygous mutation (c.1874A>T, p.Y625F) in exon 4 of the patient’s AKAP6 gene, which was predicted to be deleterious. Through an internal matchmaking effort, the authors identified another patient with intellectual disability with a de-novo truncating variant (c.1572_1573del, p.Lys525Glufs30*) in AKAP6. These two findings help suggest the possibility of AKAP6 being a bona-fide disease gene for intellectual disability in humans.
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