Table 1. Summarizing prioritized plasma protein associated with CMR and cardiac outcomes.
| Protein (UniProt ID) | Nearest druggable protein (UniProt ID) |
Druggability | Ventricle | CMR effect | Cardiac effect | Clinical development phase | No. compounds | Compound action types | CVD indication or side effects | Oncological indication or side effects |
|---|---|---|---|---|---|---|---|---|---|---|
| MANBA (O00462) | Currently not druggable | Both | Beneficial | Beneficial | 0 | 0 | ||||
| NCAM2 (O15394) | Currently not druggable | Both | Beneficial | Beneficial | 0 | 0 | ||||
| TNF12 (O43508) | Directly druggable | Left | Mixed | Beneficial | 1 | 2 | Inhibitor | ✓ | ||
| ICOSL (O75144) | Directly druggable | Left | Beneficial | Harmful | 1 | 1 | Inhibitor | |||
| BAG3 (O95817) | HSP7C (P11142) | Indirectly druggable | Both | Beneficial | Beneficial | 3 | 1 | Inhibitor | ||
| C1QC (P02747) | Currently not druggable | Both | Harmful | Beneficial | 0 | 0 | ||||
| IL6RA (P08887) | Directly drugged | Both | Mixed | Beneficial | 4 | 4 | Antagonist, inhibitor | ✓ | ✓ | |
| PATE4 (P0C8F1) | Currently not druggable | Right | Harmful | Harmful | 0 | 0 | ||||
| IL8 (P10145) | Directly druggable | Both | Mixed | Mixed | 2 | 2 | Inhibitor | ✓ | ✓ | |
| CO6A1 (P12109) | Directly drugged | Both | Mixed | Harmful | 4 | 2 | Hydrolytic enzyme | ✓ | ||
| TDGF1 (P13385) | Directly druggable | Both | Beneficial | Mixed | 1 | 1 | Binding agent | ✓ | ||
| LYAM1 (P14151) | Directly druggable | Both | Mixed | Beneficial | 3 | 3 | Antagonist, inhibitor | ✓ | ||
| PA2GA (P14555) | Directly druggable | Left | Mixed | Harmful | 3 | 2 | Inhibitor | ✓ | ||
| ISK2 (P20155) | LYAM2 (P16581) | Indirectly druggable | None | None | Harmful | 3 | 3 | Antagonist, inhibitor | ✓ | |
| UD16 (P19224) | Currently not druggable | Left | Harmful | Harmful | 0 | 0 | ||||
| CD33 (P20138) | Directly drugged | Left | Harmful | Beneficial | 4 | 6 | Binding agent, other | ✓ | ✓ | |
| CAH6 (P23280) | Directly drugged | Right | Harmful | Harmful | 4 | 1 | Inhibitor | |||
| PPAC (P24666) | 5HT1E (P28566),HDA10 (Q969S8),PDE4D (Q08499),RARA (P10276),VWF (P04275),P2RY4 (P51582),PRS7 (P35998),GBRG1 (Q8N1C3) | Indirectly drugged | Both | Beneficial | Harmful | 4 | 94 | Agonist, allosteric antagonist, antagonist, inhibitor, inverse agonist, modulator, partial agonist, positive allosteric modulator, positive modulator | ✓ | ✓ |
| TNR5 (P25942) | Directly druggable | Both | Mixed | Harmful | 2 | 5 | Agonist, antagonist, inhibitor, partial agonist | ✓ | ||
| MK03 (P27361) | Directly druggable | Right | Beneficial | Beneficial | 2 | 3 | Inhibitor | ✓ | ||
| COFA1 (P39059) | Directly drugged | Both | Mixed | Harmful | 4 | 2 | Hydrolytic enzyme | ✓ | ||
| GPC5 (P78333) | SYUA (P37840),TPH1 (P17752) | Indirectly drugged | Right | Harmful | Harmful | 4 | 4 | Inhibitor | ✓ | ✓ |
| TIE2 (Q02763) | Directly drugged | Both | Beneficial | Harmful | 4 | 8 | Inhibitor | ✓ | ✓ | |
| MFGM (Q08431) | Directly druggable | Right | Beneficial | Harmful | 1 | 1 | Binding agent | |||
| IL18R (Q13478) | IL18 (Q14116) | Indirectly druggable | Left | Beneficial | Beneficial | 2 | 2 | Cross-linking agent, inhibitor | ✓ | |
| LAMC2 (Q13753) | Directly drugged | Right | Beneficial | Harmful | 4 | 1 | Hydrolytic enzyme | ✓ | ||
| BGH3 (Q15582) | Currently not druggable | Both | Harmful | Beneficial | 0 | 0 | ||||
| ERAP2 (Q6P179) | Directly druggable | Both | Beneficial | Harmful | 2 | 1 | Inhibitor | ✓ | ||
| SPA12 (Q8IW75) | Currently not druggable | Both | Beneficial | Harmful | 0 | 0 | ||||
| PGLT1 (Q8NBL1) | Currently not druggable | Both | Beneficial | Harmful | 0 | 0 | ||||
| I17RA (Q96F46) | Directly drugged | Both | Mixed | Beneficial | 4 | 1 | Antagonist | ✓ | ||
| SLAF7 (Q9NQ25) | Directly drugged | Right | Beneficial | Harmful | 4 | 1 | Inhibitor | ✓ | ✓ | |
| ERAP1 (Q9NZ08) | Directly druggable | Both | Beneficial | Mixed | 2 | 1 | Inhibitor | ✓ |
Indirectly drugged or indirectly druggable proteins were mapped to the nearest druggable protein (fig. S8), potentially resulting in tied proteins at the same distance. Tied proteins were both included in further analyses, for example, resulting in eight nearest druggable proteins for PPAC explaining the large number of mapped compounds. For indirectly drugged/druggable proteins, the CMR and cardiac effects represent the indexing protein for which we had plasma pQTL (the first column) and the drug compound data are from the nearest druggable protein(s). The nearest druggable protein of ISK2, LYAM2, was available as pQTL data; hence, here we instead list the LYAM2 effects on CMR and cardiac traits. Clinical development phase refers to the phase of clinical testing (0 no human testing). Nomenclature: Proteins are referred to by their UniProt entry name to differentiate them from the encoding genes.