Domain structure of human SMO and variant annotation
The SMO transcript encodes a typical domain structure of a
GPCR-like signal transducer (Fig.1A, 1B) that traffics from
intracellular pools to the plasma membrane and ultimately through the
cilium following ligand stimulation. A key feature of SMO is its
heptahelical transmembrane domain, that is the site of natural and
synthetic agonist and antagonist binding as well as activating mutations
in human cancers. The seven missense variants detected among HPE
probands are described in Table 1 and their positions are annotated in
Fig.1B. The primary amino acid comparison data indicates that the mutant
residues p.R113, p.R199, p.V404, p.R772 are largely evolutionarily
conserved (Fig.1C). However, the potential consequences of the
variations are difficult to predict.