Expanded Catalog of Gold Standard Ciliary Gene List: Integration of Novel Ciliary Genes into the Ciliome

Ciliopathies are rare genetic disorders caused by mutations in genes that encode proteins critical for cilium assembly and function, affecting various subcompartments, including the axoneme, ciliary membrane, transition zone, and basal body. These mutations lead to diverse developmental and degenerative conditions across multiple organ systems. The 2021 ciliary Gold Standard gene list (688 genes) provides a foundational resource, but many ciliary genes remain unidentified or unclassified. We developed CiliaHub (https://theciliahub.github.io/), a scalable and user-friendly platform that integrates automated literature mining with expert manual curation to identify human ciliary genes. The approach combines gene names, synonyms, and targeted keywords (e.g., cilia, flagella, basal body) to extract gene-specific mentions from published studies, followed by rigorous validation through independent expert review. CiliaHub identified 2011 experimentally supported ciliary genes, including 1323 not previously listed in curated databases. Notably, some of these genes are co-found in both cilia and other organelles, such as mitochondria and lysosomes. Cross-referencing with mouse knockout model data revealed strong associations with ciliopathy-relevant phenotypes, such as infertility in Cep70 and renal defects or hearing abnormalities in genes like TMEM145. This work also provides novel ciliopathy candidate genes for further investigation. CiliaHub provides a broad platform for fundamental and translational research, enabling the effective prioritization of candidate disease genes, including recently identified ciliopathy candidates.