The increased cooperativity may act similarly to a second Leber congenital amaurosis variant, CRX K50N (Rule 11), which was previously shown to increase cooperativity on the P3 site, and thereby cause ectopic binding that silenced progenitor chromatin states rather than directing differentiation of progenitor photoreceptors (Zheng et al., 2024). Here, CRX is linked to Leber congenital amaurosis.