Ankyrin repeat domain-containing protein 26 (ANKRD26)

Ankyrin repeat domain-containing protein 26 (ANKRD26) is a cytoskeleton-associated scaffold protein characterized by the presence of ankyrin repeats that facilitate protein-protein interactions[5][7][8]. It is required for optimal proliferation and differentiation of hematopoietic progenitors in the megakaryocyte, granulocytic, and erythroid lineages, where it centrally modulates signaling via type I cytokine receptors including thrombopoietin receptor (MPL), granulocyte colony-stimulating factor receptor (G-CSFR), and erythropoietin receptor (EPOR)[1][4]. ANKRD26 expression is high in early hematopoietic progenitors and decreases with maturation, where its proper regulation is necessary for preventing hematologic dysfunctions such as thrombocytopenia (THC2; an autosomal dominant form of inherited thrombocytopenia) and, due to sensitized cytokine signaling, myeloid malignancies[1][2][4]. Outside the hematopoietic system, ANKRD26 functions in energy homeostasis, adipogenesis, and feeding behavior, with gene disruptions implicated in extreme obesity, insulin resistance, and gigantism in model organisms[6][7][3]. No direct small-molecule or biological inhibitors of ANKRD26 are clinically available; instead, its biological activity modulates responses to drugs that stimulate cytokine receptors, such as thrombopoietin mimetics (eltrombopag) used in the treatment of thrombocytopenia[1][4]. Mutations in the 5'-untranslated region (5'-UTR) of ANKRD26 are diagnostic for inherited thrombocytopenia type 2 (THC2).[2][5] Chromosomal rearrangements and gene fusions involving ANKRD26 have been reported in several human cancers, suggesting a role in tumorigenesis[3]. Altered expression or mutation of ANKRD26 may be associated with secondary safety or efficacy considerations in patients with hematological, metabolic, or oncologic disorders.

Other names

KIAA1074THC2bA145E8.1ankyrin repeat domain 26ANKRD26GNS/ANKRD26/NCKAP1L fusion

Drugs (specifically TPO mimetics such as eltrombopag) act through modulation of MPL signaling, for which ANKRD26 modulates receptor sensitivity[1][4]; no direct targeting drugs described