The NPR2 gene encodes a homodimeric transmembrane receptor called natriuretic peptide receptor B. The latter binds to its extracellular ligand; C-type natriuretic peptide (CNP), which leads to the production of cGMP from GTP.
NPR2 has 5 functional domains: an extracellular ligand-binding domain, a single membrane-spanning region, a protein kinase homology domain, a helical hinge region involved in oligomerization, and a carboxyl-terminal guanylyl cyclase catalytic domain.
The NPR2 gene is located on the short (p) arm of chromosome 9, and is 17.5 kb long with 22 exons. Mutations in NPR2 cause acromesomelic dysplasia Maroteaux type (AMDM), in which many types of mutations were identified (e.g. missense, frameshift, splice site and nonsense mutations). Moreover, obligate carriers of NPR2 mutations were shorter than average.
The mechanism by which missense mutations are thought to downregulate signaling through NPR2 involves arresting receptor trafficking at the endoplasmic reticulum due to a conformational change.
Faivre et al. (2000) demonstrated linkage to 9p13-q12 in four Turkish consanguineous families with AMDM, but excluded this locus in a fifth Lebanese family, where two sibs, born to first cousin parents, had a mild form of AMDM with less marked shortening of the extremities and almost normal vertebra.