# Systematic discovery of retina-enriched Rik genes identifies 1190005I06Rik as a novel modulator of visual signalling

## TL;DR

This study identifies a previously unknown gene, 1190005I06Rik, that plays a role in visual signaling in the retina and highlights many other uncharacterized genes that may be important for retinal function and disease.

## Contribution

The study systematically identifies and functionally characterizes a novel retina-enriched Rik gene, 1190005I06Rik, as a modulator of visual signaling.

## Key findings

- 44 Rik genes show robust retina-specific expression, with some being rodent-specific and others conserved.
- 1190005I06Rik knockout mice exhibit altered electroretinogram responses and light-avoidance behavior, indicating a role in visual signaling.
- The study provides a curated atlas of retina-enriched Rik genes, expanding the molecular understanding of retinal function.

## Abstract

High‑throughput transcriptome projects have revealed thousands of mammalian genes with little or no functional annotation. Among these are hundreds of loci assigned provisional “Rik” identifiers following discovery in the RIKEN cDNA annotation effort. Although often dismissed as genomic dark matter, such genes may encode tissue‑restricted proteins that modulate physiologic functions and influence disease. The retina is a highly specialised neural tissue and a common site of inherited disorders; understanding its molecular repertoire could illuminate novel therapeutic avenues.

We integrated bulk RNA‑seq from ten adult mouse tissues, evolutionary and domain analysis, single‑cell RNA‑seq, and CRISPR/Cas9 gene disruption to systematically catalogue protein‑coding Rik genes enriched in the retina and test the function of a representative gene.

A rigorous differential expression analysis identified 44 Rik genes with robust retina‑specific expression compared with nine non‑retinal tissues. Many of these genes lack orthologues beyond rodents, while others show broad conservation, illustrating a continuum from lineage‑restricted to conserved retinopathy candidates. Single‑cell transcriptomics revealed that these genes are expressed across retinal cell types, with the highest aggregate expression in cone photoreceptors and inner interneurons. To evaluate physiological significance, we generated a 1190005I06Rik knockout mouse. Although retinal architecture appeared normal, loss of 1190005I06Rik enhanced electroretinogram b‑wave amplitudes and altered light‑avoidance behaviour, indicating that this previously uncharacterised gene acts as a negative modulator of visual signalling.

We present a curated atlas of retina‑enriched Rik genes and demonstrate that 1190005I06RIK modulates retinal circuit function. This resource expands the molecular landscape of the retina and provides new candidates for the genetic basis of inherited retinal disease. Our findings underscore that unannotated genes may exert measurable effects on sensory processing and warrant systematic exploration in the context of human ocular disorders.

The online version contains supplementary material available at 10.1186/s12967-026-07769-z.