Categories: Vision / eye phene , Normal phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 180380 (gene) , 610445 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2023

Species-specific description: Yamaguchi et al. (2023): "The whale shark, which dives into the deep sea of nearly 2,000 meters besides near-surface filter feeding, was previously shown to possess the ‘blue-shifted’ rhodopsin (RHO), which is a signature of deep-sea adaptation. In this study, our spectroscopy of recombinant whale shark RHO mutants revealed that this blue shift is caused dominantly by an unprecedented spectral tuning site 94. In humans, the mutation at the site causes congenital stationary night blindness (CSNB) by reducing the thermal stability of RHO. "

Molecular basis: Yamaguchi et al. (2023) "scrutinized the sequence alignment of RHO orthologs of these sharks and their relatives. This analysis revealed two amino acid residues 94 and 178 substituted exclusively in the whale shark (Ala94 and Phe178) and no substitution at previously characterized spectral tuning sites ... . We examined the effect of each of these substitutions with site-directed mutagenesis, which resulted in the shifts of the λmax of whale shark RHO A94T and F178Y mutants toward longer wavelengths by 19 and 3 nm, respectively, compared with that of the wild type ... . Conversely, mutants with substitutions at these sites (T94A and Y178F) of zebra shark recapitulated the blue shift by 19 and 3 nm ... . This result shows a dominant effect of Ala94 accounting for the blue shift of whale shark RHO. At site 94 of RHO, no case of natural substitution has been reported as responsible for spectral tuning, but interestingly, the T94I mutation is known to cause a human disease congenital stationary night blindness (CSNB) ... ."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing