FIGURE 5.

Interactome, N-terminal splicing variations and pathogenic variants of MYO7A (A) Interacting partners of MYO7A. SANS and harmonin isoform b (harmonin b) bridge interactions with other partners. Serine and threonine-rich (PST) sequence of harmonin b can bind to F-actin (Grillet et al., 2009). SAH domain of MYO7A has a weak dimerization activity (Sakai et al., 2011; Liu et al., 2021). SANS, PCDH15 and CDH23 can dimerize with each other (Adato et al., 2005; Dionne et al., 2018; Jaiganesh et al., 2018). The tail of MYO7A can inhibit the motor function (autoinhibition). (B) Different N-termini of two MYO7A isoforms. The canonical isoform has an eleven amino-acid extension at the N-terminus (MYO7A-C), while the short isoform does not (MYO7A-S). (C) Mapping of pathogenic and likely pathogenic MYO7A variants. Obtained and classified as described for Figure 3 adding a category, VIS, to indicate variants associated with retinal dysfunction but not with hearing loss. Nonsense and frameshift variants in MYO7A usually result in autosomal recessive Usher syndrome or nonsyndromic hearing loss (yellow rectangles), but some are additionally associated with autosomal dominant nonsyndromic hearing loss (pink rectangle). Overlapping phenotypic categories are observed also for missense mutations (examples shown by open and closed arrowheads). Missense variants are reported for the first methionine codon of the N-terminal extension (p.Met1Val and p. Met1Ile, arrows).