A multiomics approach reveals novel regulators of plasma factor V levels, highlighting CLEC4M as a clearance receptor.

Munsch G, Mohapatra AK, van Hylckama Vlieg A, Kleber ME, Martinez-Perez A, Le NQ, Hindberg KD, Dusart P, Germain M, Thibord F, Deleuze JF, Delgado GE, Goumidi L, Suchon P, Saut N, Souto JC, Butler LM, Soria JM, Hansen JB, März W, Rosendaal FR, Castoldi E, Peiretti F, Sabater-Lleal M, Trégouët DA, Morange PE

Blood 146 (5) 628-637 [2025-07-31; online 2025-05-13]

Coagulation factor V (FV) is a key protein in maintaining the hemostatic balance, with abnormal plasma levels associated with both thrombotic and hemorrhagic conditions. We propose a comprehensive bioinformatic analysis integrating large-scale proteogenomics and transcriptomic data from original and public data sets. We identify a biological fingerprint of 26 new proteins and loci involved in the regulation of plasma FV levels. Furthermore, the messenger RNA expression levels of 10 of these components demonstrate strong correlation in the liver. In addition, we provide experimental evidence for the involvement of one of the newly identified players (CLEC4M) in the clearance of FV. This work opens new avenues for a better understanding of the physiological processes involved in thrombotic and bleeding disorders.

PubMed 40359434

DOI 10.1182/blood.2024027006

Crossref 10.1182/blood.2024027006

pii: 537238