ACVRL1

Function

This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia (HHT) type 2, also known as Rendu-Osler-Weber syndrome 2.

Pathology

Germline mutations of ACVRL1 are associated with:

• hereditary hemorrhagic telangiectasia type 2 (Rendu-Osler-Weber syndrome 2)
• Pulmonary arteriovenous malformations

Somatic mosaicism in ACVRL1 are associated with severe pulmonary arterial hypertension.

ACVRL1 directly interacts with low-density lipoprotein (LDL), which implies that it might initiate the early phases of atherosclerosis.

Abnormal activity of ACVRL1 has been found to be closely associated with idiopathic pulmonary arterial hypertension.

As a drug target

• Dalantercept is an experimental ALK1 inhibitor.

Closely/family related kinases

(Not to be confused with anaplastic lymphoma kinase (ALK) )

ALK4 is ACVR1B, ALK7 is ACVR1C, and ALK5 is [part of] the TGF-β type I receptor.

References

References

1. (October 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene.
2. (June 1996). "Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2". Nature Genetics.
3. "Entrez Gene: ACVRL1 activin A receptor type II-like 1".
4. (July 2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". Journal of Medical Genetics.
5. (April 2014). "Pulmonary arterio-venous malformations in a patient with a novel mutation in exon 10 of the ACVRL1 gene". Acta Clinica Belgica.
6. (August 2014). "Somatic mosaicism in ACVRL1 with transmission to several offspring affected with severe pulmonary arterial hypertension". American Journal of Medical Genetics. Part A.
7. (November 2016). "Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells". Nature Communications.
8. (2015). "Activin receptor inhibitors--dalantercept". Current Oncology Reports.
9. (July 2002). "Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542". Molecular Pharmacology.