Eye disorders

Blindness; Oguchi disease 2; Fundus albipunctatus; Oguchi disease 1; Night blindness, Congenital stationary, 1d, autosomal recessive; Cone dystrophy; Night blindness, Congenital stationary, 1a, X-linked

Oguchi disease is an autosomal recessive eye disease that is a form of congenital stationary eye blindness, which is associated with discolouration of the fundus and impaired dark adaptation. Fundus albipunctatus is a fundus dystrophy characterized by the presence of uniform white dots over the entire structure, with maximal density in the midperiphery and no involvement of the macula. Congenital stationary night blindness is a rare X-linked non-progressive retinal disorder characterized by impaired night vision and often associated with nystagmus and myopia. Mutations in the RHOK gene have been observed in patients with Oguchi disease, including a deletion mutation encompassing exon 5, a missense mutation in the catalytic domain (V380D), and a frameshift mutation at Ser536 resulting in C-terminal truncation of the protein and the absence of isoprenylation, which is required for RHOK activation. Therefore, these mutation are predicted to result in a loss-of-function in the kinase catalytic activity of the RHOK protein, indicating a role for overactive rhodopsin and phototransduction in the pathogenesis of Oguchi disease.
 

RHOK may be a tumour requiring protein (TRP), since it displays extremely low rates of mutation in human cancers.
 

The COSMIC website notes an up-regulated expression score for RHOK in diverse human cancers of 484, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0 % in 24984 diverse cancer specimens. This rate is -98 % lower than the average rate of 0.075 % calculated for human protein kinases in general. Such a very low frequency of mutation in human cancers is consistent with this protein kinase playing a role as a tumour requiring protein (TRP).

Highest percent mutation rates per 100 amino acids length in human cancers: 0.04 % in 833 ovary cancers tested.

None > 1 in 20,267 cancer specimens

No deletions, insertions or complex mutations are noted on the COSMIC website.