EDNRA gene

The EDNRA gene (EDNRA stands for: Endothelin Receptor Type A) is a protein-coding gene located on chromosome 4q31.22-q31.23. An important paralog of this gene is EDNRB. Alternative splicing leads to several transcript variants.

This gene encodes the receptor for endothelin-1, a peptide that plays a role in severe and long-lasting vasoconstriction. This peptide is encoded by the endothelin-1 gene. Its receptor associates with guanine nucleotide-binding (G) proteins, and this coupling activates a phosphatidylinositol-calcium second messenger system. Polymorphisms in this gene have been associated with resistance to migraine headaches.

Systemic scleroderma: Circulating functional autoantibodies directed against the vascular angiotensin II receptor type 1 and the endothelin-1 receptor type A have been reported and are thought to play a pathogenic role (Avouac J et al. 2015; Cabral-Marques O et al. 2017). However, their exact involvement in pathogenesis remains to be determined, and it is also not yet clear whether they can be used as biomarkers or even represent therapeutic targets.

The endothelin A receptor (ETA receptor) encoded by the EDNRA gene is a member of the endothelin receptor group of G-protein-coupled receptors, which also includes ETB. The receptor mediates its action by associating with G-proteins that activate a phosphatidylinositol calcium second messenger system. The order of binding affinity for ET-A is: ET1 > ET2 >> ET3. These receptors are mainly localized in the vascular smooth muscle, where they play a role in vasoconstriction and cell proliferation.

Diseases associated with EDNRA include mandibulofacial dysostosis with alopecia and migraine with or without aura 1.

1. Avouac J et al. (2015) Autoantibodies against endothelin 1 type a receptor are strong predictors of digital ulcers in systemic sclerosis. J Rheumatol 42: 1801-1807.
2. Cabral-Marques O et al. (2017) Functional autoantibodies targeting G protein-coupled receptors in rheumatic diseases. Nat Rev Rheumatol13: 648-656.