# A Novel A‐Kinase‐Anchoring Protein 9 Variant in Premature Coronary Artery Disease: A Case Series

## TL;DR

A new AKAP9 gene variant is linked to early-onset heart disease in a Chinese family, suggesting a genetic cause for premature coronary artery disease.

## Contribution

Identifies a novel AKAP9 variant associated with premature CAD and demonstrates its functional impact on protein interactions.

## Key findings

- The AKAP9 c.6406C>G variant is strongly linked to premature CAD in a Chinese pedigree.
- The variant reduces interaction between AKAP9 and PRKAR2A, suggesting a functional mechanism.
- This is the first report of this variant in premature CAD patients.

## Abstract

Familial premature coronary artery disease (CAD) is often associated with genetic variants. This study investigated potential causal variants in a Chinese pedigree with premature CAD.

In total, nine family members were included in the study (six CAD patients and three unaffected controls). Whole‐exome sequencing (WES) was performed on six family members (including four patients and two unaffected controls), and the candidate variant was further validated by Sanger sequencing in four individuals.

A strong linkage between c.6406C>G (p.Gln2136Glu; NM_005751.5) in AKAP9 (A‐KINASE ANCHOR PROTEIN 9; OMIM 604001) and premature CAD was detected in the pedigree. Functional analysis revealed that the c.6406C>G variant in AKAP9 decreased the interaction between AKAP9 and PRKAR2A. This association was first detected in premature CAD patients.

Our findings indicate that c.6406C>G in the AKAP9 gene could be a causal variant for premature CAD in the Chinese population.

AKAP9 Q2136E mutation disrupts AKAP9–PRKAR2A interaction and may contribute to early‐onset CAD.