DEAD-box Helicase 41 (DDX41) is a member of the DExD/H-box helicase family that has a variety of cellular functions. Of note, germline and somatic mutations in the DDX41 gene are prevalently found in myeloid malignancies. Here, we present a comprehensive and analytic review covering relevant clinical, translational and basic science findings on DDX41. We first describe the initial characterisation of DDX41 mutations in patients affected by myelodysplastic syndromes, their associated clinical characteristics, and current treatment modalities. We then cover the known cellular functions of DDX41, spanning from its discovery in Drosophila as a neuroregulator through its more recently described roles in inflammatory signalling, R-loop metabolism and snoRNA processing. We end with a summary of the identified basic functions of DDX41 that when perturbed may contribute to the underlying pathology of haematologic neoplasms.
Keywords: DDX41; DEAD-box helicase; R-loops; acute myeloid leukaemia; cGAS-STING; genomic instability; germline predisposition; haematopoiesis; inflammation; myelodysplastic syndrome.
© 2022 Federation of European Biochemical Societies.