IQCB1, also known as NPHP5, encodes the ciliary protein nephrocystin 5. It is involved in ciliopathy-related processes and is crucial for ciliary function. The protein interacts with other ciliopathy-associated proteins like CEP290 and EPB41L5, regulating the composition of the ciliary base and centrosome [4]. It plays a significant role in multiple biological processes, with its dysfunction linked to various diseases.

In a Nphp5-knockout mouse model, absence of scotopic and photopic electroretinogram responses was observed, resembling Leber congenital amaurosis. There was outer segment transmembrane protein accumulation in the endoplasmic reticulum, and aberrant transition zones of reduced diameter in photoreceptors. The knockout mice also had complete photoreceptor degeneration by 1 month of age, highlighting the essential role of IQCB1 in photoreceptor outer segment formation [9]. In human studies, IQCB1 mutations are associated with Leber congenital amaurosis, Senior-Loken syndrome (characterized by nephronophthisis and retinal degeneration), and non-syndromic IQCB1-retinopathy. In liver cancer, elevated IQCB1 expression is related to poor prognosis, and it shows correlations with markers like MKI67, HBV, HCV, and AFP, as well as associations with immune infiltration and checkpoint mechanisms [1,2,3,5,6,7,8].

In conclusion, IQCB1 is essential for ciliary function and photoreceptor outer segment formation. Its knockout models have been instrumental in revealing its role in retinopathies. In addition, its associations in liver cancer suggest its potential as a diagnostic and prognostic marker. Research on IQCB1 provides insights into the mechanisms of ciliopathies and liver cancer, potentially guiding future therapeutic strategies.

References:

1. Han, Dongmei, Ling, Bin, Wu, Caihong, Jin, Hao. 2024. The role of IQCB1 in liver cancer: a bioinformatics analysis. In Translational cancer research, 13, 5021-5036. doi:10.21037/tcr-24-110. https://pubmed.ncbi.nlm.nih.gov/39430824/

2. Sen, Sagnik, Fabozzi, Lorenzo, Fujinami, Kaoru, Georgiou, Michalis, Michaelides, Michel. 2024. IQCB1 (NPHP5)-Retinopathy: Clinical and Genetic Characterization and Natural History. In American journal of ophthalmology, 264, 205-215. doi:10.1016/j.ajo.2024.03.009. https://pubmed.ncbi.nlm.nih.gov/38522724/

3. Wang, Junwen, Li, Shiqiang, Jiang, Yi, Wang, Panfeng, Zhang, Qingjiong. 2023. Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4. In American journal of ophthalmology, 252, 188-204. doi:10.1016/j.ajo.2023.03.025. https://pubmed.ncbi.nlm.nih.gov/36990420/

4. Yu, Tiffany, Matsuda, Miho. 2020. Epb41l5 interacts with Iqcb1 and regulates ciliary function in zebrafish embryos. In Journal of cell science, 133, . doi:10.1242/jcs.240648. https://pubmed.ncbi.nlm.nih.gov/32501287/

5. Estrada-Cuzcano, Alejandro, Koenekoop, Robert K, Coppieters, Frauke, Cremers, Frans P M, den Hollander, Anneke I. 2011. IQCB1 mutations in patients with leber congenital amaurosis. In Investigative ophthalmology & visual science, 52, 834-9. doi:10.1167/iovs.10-5221. https://pubmed.ncbi.nlm.nih.gov/20881296/

6. Kruczek, Kamil, Qu, Zepeng, Welby, Emily, Brooks, Brian P, Swaroop, Anand. 2022. In vitro modeling and rescue of ciliopathy associated with IQCB1/NPHP5 mutations using patient-derived cells. In Stem cell reports, 17, 2172-2186. doi:10.1016/j.stemcr.2022.08.006. https://pubmed.ncbi.nlm.nih.gov/36084637/

7. Yu, Pei-Hua, Kuo, Yuh-Ren, Altmüller, Janine, Hwang, Daw-Yang. 2018. Senior-Løken syndrome with IQCB1 mutation in Taiwan. In The Kaohsiung journal of medical sciences, 34, 588-589. doi:10.1016/j.kjms.2018.03.010. https://pubmed.ncbi.nlm.nih.gov/30309488/

8. Vincent, A, AlAli, A, MacDonald, H, VandenHoven, C, Héon, E. 2017. Specific retinal phenotype in early IQCB1-related disease. In Eye (London, England), 32, 646-651. doi:10.1038/eye.2017.283. https://pubmed.ncbi.nlm.nih.gov/29219953/

9. Ronquillo, Cecinio C, Hanke-Gogokhia, Christin, Revelo, Monica P, Jiang, Li, Baehr, Wolfgang. 2016. Ciliopathy-associated IQCB1/NPHP5 protein is required for mouse photoreceptor outer segment formation. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 30, 3400-3412. doi:. https://pubmed.ncbi.nlm.nih.gov/27328943/