Table 2.
Examples of known HKMDs with approved drugs.
| Gene | LOF | Allele freq. | Effect size | Phenotype | Approved drug | References |
|---|---|---|---|---|---|---|
| APOC3 | T | 0.0040 (Danish) | 44% for TG; 41–36% for CHD | Lower triglyceride and protection from coronary heart disease | (2019) volanesorsen | 29,30 |
| 0.0067 (European and African) | 39% for TG; 40% for CHD | |||||
| CCR5 | M | 0.092 (European) | 100% resistant | Resistance to HIV/AIDS | (2007) maraviroc | 31,32 |
| FAAH | T** | Not available | Not available | Reduced sensitivity to pain and generally lower anxiety levels | Not applicable | 33 |
| PCSK9 | T | 0.026 (African) | 28% for LDL; 88% for CHD | Lower serum LDL and protection from coronary heart disease | (2015) alirocumab, evolocumab | 18,19 |
| SOST | M | Not available | Not available | Higher bone density | (2019) romosozumab | 21,22 |
The column LOF indicates if the phenotype is observed in heterozygotes (T) or homozygotes (M). For FAAH, the notation T** indicates that the trait requires heterozygous mutations in two different but functionally related loci. FAAH is a promising alternative for pain-relieving drugs inspired by LOFs in SCN9A34. Allele frequency and effect size, when provided, come from the cited references.
TG triglyceride, LDL low-density lipoproteins, CHD coronary heart disease.