Other downregulated proteins are also associated with osteogenic differentiation, e.g., A2M was identified to be marker of later, calcific stage of CAVD according to spatiotemporal multi-omics data (33); IGF2R is involved in vascular calcification through Erk1/2 and Akt signaling (34); apolipoprotein CIII (APOC3) is associated with CAVD progression (35). Here, IGF2R is linked to congenital bilateral aplasia of vas deferens from CFTR mutation.