Fig. 4

Schematic representation showing 40 reported FZD4 missense mutations dispersed across the protein and are associated with pathogenic FEVR. FZD4 contains a signal sequence at the amino (N′) terminus from amino acids 1 and 36/37; a conserved FZ-CRD region highlighted in green of approximately 122 amino acids in the extracellular domain containing a motif of 10 spaced cysteines between amino acid positions 40 through 161; a seven-pass TMD region labelled TM1–7 within amino acid positions 210 through 514; and a cytoplasmic domain with a KTXXXW motif found at amino acid positions 499 through 504, and a PDZ motif located close to the C′ terminal at amino acid positions 535 through 537. The two potential N-glycosylation sites are indicated by black stars at amino acid positions 59 and 144. Smallwood et al. have shown that the binding of Norrin to the CRD domain of FZD4 extends to include residue C204 (Smallwood et al. 2007). Amino acid positions and domains can be accessed from https://www.uniprot.org/uniprot/Q9ULV1