The CYB5R3 T117S Missense Variant is Associated with Attenuated Riociguat Efficacy in Sickle Cell Disease

K Katherine C Wood (University of Pittsburgh, Pittsburgh, Pennsylvania, United States) S Seyed Mehdi Nouraie (University of Maryland, United States) M Mark T Gladwin (University of Maryland, United States) E Enrico M Novelli (University of Pittsburgh, Pittsburgh, Pennsylvania, United States) V Victor R Gordeuk (University of Illinois at Chicago, Chicago, Illinois, United States) C Claudia R. Morris (Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta) C Caterina P Minniti (Albert Einstein College of Medicine, Chevy Chase, Maryland, United States) K Kenneth I Ataga (University of Tennessee Health Science Center at Memphis, Memphis, Tennessee, United States) P Payal Chandarana Desai (Levine cancer Institute, Wake Forest school of medicine, Charlotte, Charlotte, North Carolina, United States) K Kaleab Z Abebe (University of Pittsburgh, Pittsburgh, Pennsylvania, United States) A Adam C Straub (Univeristy of Pittsburgh, Pittsburgh, Pennsylvania, United States)

Abstract

Sickle cell disease attenuates nitric oxide signaling, limiting soluble guanylyl cyclase (sGC) stimulation needed for hemo-vascular function. Cytochrome b5 reductase 3 (CYB5R3) regulates sGC activity and expression. We show CYB5R3 T117S associates with reduced efficacy of the sGC stimulator riociguat. (NCT02633397)

Article Details

Journal Blood
Volume / Issue Vol. 1, Issue 1
Published July 08, 2026
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (11)

K

Katherine C Wood

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

S

Seyed Mehdi Nouraie

University of Maryland, United States

M

Mark T Gladwin

University of Maryland, United States

E

Enrico M Novelli

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

V

Victor R Gordeuk

University of Illinois at Chicago, Chicago, Illinois, United States

C

Claudia R. Morris

Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta

C

Caterina P Minniti

Albert Einstein College of Medicine, Chevy Chase, Maryland, United States

K

Kenneth I Ataga

University of Tennessee Health Science Center at Memphis, Memphis, Tennessee, United States

P

Payal Chandarana Desai

Levine cancer Institute, Wake Forest school of medicine, Charlotte, Charlotte, North Carolina, United States

K

Kaleab Z Abebe

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

A

Adam C Straub

Univeristy of Pittsburgh, Pittsburgh, Pennsylvania, United States