Table 1. Summary of disease-relevant SNPs in human cardiac Ago2 clusters.
| Gene | Disease relevance | SNP ID | Alleles (MAF*) | Minor allele effect | Comments |
|---|---|---|---|---|---|
| BNIP3 | MI and HF | rs4550 | G/A (32%) | Disrupts miR-27 seed | BNIP3 is elevated in ischemic heart failure and promotes cell death |
| CMYA5 | Cardiomyopathy | rs11323646 | T/- (28%) | Disrupts miR-144 seed | Gene encodes myospryn (interacts with z-discs and calcineurin) |
| DAG1 | DCM | rs1801143 | C/T (22%) | Enhances miR-1 3′ pairing | Mutations in this dystroglycan gene cause dilated cardiomyopathy |
| GJA1 | DCM & Arrhythmia | rs111878880 | T/C (6%) | Adjacent to miR-30 seed Disrupts miR-29 seed | Encodes Cx43, a gap junction protein that is critical for cardiac conductance |
| LAMA2 | DCM | rs1049476 | T/C (21%) | Disrupts miR-126 seed Adjacent to miR-29 seed | Mutations in this extracellular laminin protein cause dilated cardiomyopathy |
| LPL | Atherosclerosis | rs1059611 | T/C (13%) | Disrupts miR-136 seed | 3′UTR SNP associated with serum lipid levels in several GWAS studies |
| MYOZ2 | HCM | rs9995277 | G/A (29%) | Disrupts miR-30 seed | Mutations in this z-disc and calcineurin-tethering protein cause HCM |
| NEXN | DCM and HCM | rs145017889 | AGTGTTG/- (7%) | Disrupts miR-181 seed | Mutations in this F-actin binding protein destabilize cardiac z-discs |
| SCN5A | Brugada syndrome, QT, QRS interval | rs1805126 | T/C (49%) | Adjacent to miR-24 site | Synonymous CDS SNP associated with heart rhythm changes in GWAS studies |
| TTN | DCM and HCM | rs16866531 rs2303832 | A/G (3.9%) A/T (3.0%) | Disrupts miR-1 seed Disrupts miR-133 seed | These SNPs may serve a modifiers of the many pathogenic mutations in titin |
*MAF = minor allele frequency, MI = myocardial infarction, HF = heart failure, DCM = dilated cardiomyopathy, HCM = hypertrophic cardiomyopathy.