Send to

Choose Destination
Cytokine Growth Factor Rev. 2016 Feb;27:93-104. doi: 10.1016/j.cytogfr.2015.12.007. Epub 2015 Dec 28.

Common mutations in ALK2/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders.

Author information

Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States. Electronic address:
Departments of Orthopaedic Surgery and Genetics, and the Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 United States. Electronic address:


Activin receptor-like kinase-2 (ALK2), the product of ACVR1, is a member of the type I bone morphogenetic protein (BMP) receptor family. ALK2 exerts key and non-redundant roles in numerous developmental processes, including the specification, growth and morphogenesis of endochondral skeletal elements. There is also strong evidence that BMP signaling plays important roles in determination, differentiation and function of neural cells and tissues. Here we focus on the intriguing discovery that common activating mutations in ALK2 occur in Fibrodysplasia Ossificans Progressiva (FOP) and Diffuse Intrinsic Pontine Gliomas (DIPGs), distinct pediatric disorders of significant severity that are associated with premature death. Pathogenesis and treatment remain elusive for both. We consider recent studies on the nature of the ACVR1 mutations, possible modes of action and targets, and plausible therapeutic measures. Comparisons of the diverse - but genetically interrelated - pathologies of FOP and DIPG will continue to be of major mutual benefit with broad biomedical and clinical relevance.


ACVR1; ALK2; BMP signaling; Diffuse Intrinsic Pontine Gliomas; Fibrodysplasia Ossificans Progressiva; Orphan diseases

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center