Figure 2.

Human Mutations in ARL13B Occur in Conserved Residues and Interfere with Evolutionarily Conserved Functions

(A) Domain structure of ARL13B protein, with GTP binding, coiled-coil, and proline-rich domains. Red indicates conserved regions involved in GTP binding. Mutations are indicated along the top.

(B) Evolutionary conservation of ARL13B, showing that each mutated residues is conserved at least to Danio rerio (zebrafish).

(C–F) Wild-type zebrafish have straight tails and absence of cystic kidney. Noninjected arl13b^sco/sco embryos have curved tails (red arrow) and cystic kidneys (double red arrow). The arl13b^sco/sco embryos injected with human wild-type ARL13B RNA show rescue of the curved tail and absence of cystic kidney. The human p.R79Q and p.R200C mutant ARL13B RNA failed to rescue either phenotype in the majority of embryos, although about 15%–24% showed evidence of rescued phenotype, suggesting a hypomorphic allele. A control amino acid substitution (p.S371I) in ARL13B showed a rescue effect similar to wild-type (not shown).