Ciliopathies

Genetic disorders caused by defects in genes related to the primary CILIUM; BASAL BODY; or CENTROSOME. Primary features may include obesity, SKELETAL DYSPLASIA; POLYDACTYLY and malformations that primarily involve the liver, eye or kidneys.

Also Known As:

Networked: 604 relevant articles (7 outcomes, 28 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Retinal Degeneration
2.	Leber Congenital Amaurosis
3.	Cystic Kidney Diseases (Cystic Kidney Disease)
4.	Ciliopathies
5.	Inborn Genetic Diseases (Disease, Hereditary)

Experts

1.	Katsanis, Nicholas: 23 articles (11/2020 - 10/2007)
2.	Roepman, Ronald: 23 articles (11/2020 - 11/2008)
3.	Hildebrandt, Friedhelm: 21 articles (01/2021 - 06/2007)
4.	Johnson, Colin A: 19 articles (01/2022 - 07/2007)
5.	Saunier, Sophie: 17 articles (01/2022 - 07/2007)
6.	Khanna, Hemant: 15 articles (01/2021 - 02/2008)
7.	Giles, Rachel H: 15 articles (10/2019 - 10/2010)
8.	Davis, Erica E: 14 articles (11/2020 - 11/2008)
9.	Beales, Philip L: 14 articles (01/2018 - 10/2007)
10.	Sayer, John A: 13 articles (01/2022 - 03/2012)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Ciliopathies:

1.	Proteins (Proteins, Gene)FDA Link 01/01/2017 - "The vast majority of complexes in our map are significantly enriched with literature annotations, and the map overall shows improved coverage of many disease-associated proteins, as we describe in detail for ciliopathies. " 09/01/2017 - "The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. " 01/01/2022 - "While ciliopathies caused by loss of ciliated proteins have been extensively documented, several studies suggest that alterations of GA and GA-associated proteins can also affect ciliogenesis. " 01/01/2022 - "In the present study, we identified the Sdccag8 C-terminal region (Sdccag8-C) as a module that interacts with the ciliopathy proteins, Ick/Cilk1 and Mak, which were shown to be essential for the regulation of ciliary protein trafficking and cilia length in mammals in our previous studies. " 11/01/2020 - "Genetic studies have demonstrated that mutations affecting PC proteins or its anchoring structure, the basal body, underlie a class of human disorders (known as ciliopathies) characterized by a constellation of clinical signs. "
2.	Rhodopsin (Visual Purple)IBA 10/01/2019 - "This study unveiled a novel role of lysosome-mediated degradation in causing inherited disorders manifested by mislocalization of ciliary receptors.SIGNIFICANCE STATEMENT Retinal ciliopathy is the most common form of inherited blinding disorder frequently manifesting rhodopsin mislocalization. " 08/21/2013 - "Rhodopsin mislocalization is associated with blinding diseases called retinal ciliopathies. " 11/14/2019 - "Testing of this hypothesis in transient and stable zebrafish genetic models showed this posit to be true; suppression or ablation of usp35 ameliorated hallmark ciliopathy defects including impaired convergent extension (CE), renal tubule convolution, and retinal degeneration with concomitant clearance of effectors such as β-catenin and rhodopsin. " 01/01/2016 - "Retinal remodeling instigated by aberrant trafficking of proteins encompasses many forms of retinal degenerations, such as the diverse forms of retinitis pigmentosa (RP) and disorders that resemble RP through mutations in the rhodopsin gene, retinal ciliopathies, and some forms of glaucoma and age-related macular degeneration (AMD). " 07/01/2012 - "Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3',5'-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. "
3.	Biomarkers (Surrogate Marker)IBA 01/01/2023 - "Collectively, the integration of these data sets will be beneficial for the comprehensive understanding of ciliary structures and exploring potential biomarkers and therapeutic targets for ciliopathies." 11/01/2020 - "The present article describes the most recent proteomic and metabolomic studies exploring kidney dysfunction in the setting of ciliopathies, showing the potential of these methodologies in the elucidation of disease pathophysiology and in the discovery of biomarkers." 01/01/2021 - "Novel biomarkers of ciliary extracellular vesicles interact with ciliopathy and Alzheimer's associated proteins." 01/01/2021 - "Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. " 01/01/2021 - "While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. "
4.	CateninsIBA 03/01/2015 - "In this review, we summarize correlation among primary cilium,Wnt/β-catenin signaling,Wnt/PCP signaling and ciliopathies. " 06/01/2011 - "The cilium, through regulated intraflagellar transport, diverts Jouberin (Jbn), a ciliopathy protein and context-specific Wnt pathway regulator, away from the nucleus and limits β-catenin nuclear entry. " 11/14/2019 - "Testing of this hypothesis in transient and stable zebrafish genetic models showed this posit to be true; suppression or ablation of usp35 ameliorated hallmark ciliopathy defects including impaired convergent extension (CE), renal tubule convolution, and retinal degeneration with concomitant clearance of effectors such as β-catenin and rhodopsin. " 10/01/2017 - "Based on the established connection between β-catenin signaling and renal ciliopathies, and on data from our and other laboratories showing striking similarities of this disease and cancer, we evaluated the use of an orally bioavailable small molecule, KPT-9274 (a dual inhibitor of the protein kinase PAK4 and nicotinamide phosphoribosyl transferase), for treatment of ADPKD. "
5.	Retinaldehyde (Retinal)IBA 01/01/2023 - "Our study identifies effective drug candidates in preclinical studies of CEP290 retinal ciliopathies through cross-species drug discovery using iPSC-derived organoids, highlights the impact of proteostasis in the pathogenesis of ciliopathies, and provides new insights for treatments of retinal neurodegeneration. " 01/01/2019 - "The study of retinal ciliopathies has been limited by a lack of retinal cell lines. " 06/26/2023 - "No treatments are available for patients with C2orf71 retinal ciliopathies exhibiting a severe clinical phenotype. " 01/01/2023 - "In this article, we review current protocols to differentiate human pluripotent stem cells into retinal cell types, and discuss how these cellular and/or organoid models can be utilized to interrogate pathobiology of ciliopathies affecting the retina and for testing prospective treatments." 11/24/2022 - "Biallelic Inactivating TUB Variants Cause Retinal Ciliopathy Impairing Biogenesis and the Structure of the Primary Cilium."
6.	Phosphotransferases (Kinase)IBA 01/01/2019 - "Loss-of-function mutations in the human ICK (intestinal cell kinase) gene cause dysfunctional primary cilia and perinatal lethality which are associated with human ciliopathies. " 03/09/2023 - "This review aims to describe the possibilities of using kinase inhibitors in genetic pathologies such as tuberous sclerosis, RASopathies, and ciliopathies, describing the various pathways involved and the possible targets already identified or currently under study." 01/01/2018 - "Several missense mutations in intestinal cell kinase (ICK) gene lead to endocrine-cerebro-osteodysplasia syndrome or short rib-polydactyly syndrome, lethal recessive developmental ciliopathies. " 08/22/2013 - "NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. " 12/20/2021 - "Here, we review the involvement of primary cilia-associated signaling through aurora A and AKT kinases with respect to cancer, obesity, and other ciliopathies."
7.	ProteomeIBA 01/01/2023 - "Primary and motile cilia share defined core ultra-structures with an overlapping proteome, and human disease phenotypes can reflect both primary and motile ciliopathies. " 01/01/2023 - "Understanding the role of proteome balance in the pathogenesis of the clinical manifestations of ciliopathies may pave the way to the identification of a wide range of putative novel therapeutic targets for these conditions." 11/01/2021 - "Interestingly, the Human Phenotype Ontology database lists numerous disorders that display clinical features reminiscent of ciliopathies but do not involve defects in the centriole-cilium proteome. " 01/01/2021 - "The broad applicability of quantitative ciliary proteome profiling promises a rapid characterization of ciliopathies and their underlying signaling malfunctions." 10/01/2019 - "Changes in the urinary extracellular vesicle proteome are associated with nephronophthisis-related ciliopathies."
8.	TubulinIBA 01/01/2018 - "Our study reveals a paradigm that tubulin polyglutamylation is a major contributor for cilia signaling and suggests a potential therapeutic strategy by targeting polyglutamylation machinery to promote ciliary targeting of signaling machineries and correct signaling defects in ciliopathies." 10/01/2020 - "elegans genes important for neuronal and ciliary stability, our work may inform research into the roles of the tubulin code in human ciliopathies and neurodegenerative diseases." 12/01/2020 - "Abnormal tubulin acetylation has been implicated in neurodegenerative disorders, ciliopathies, and cancers. " 06/15/2014 - "Only ccp5 knockdown increases cilia tubulin glutamylation, induces ciliopathy phenotypes, including axis curvature, hydrocephalus, and pronephric cysts, and disrupts multicilia motility, suggesting that Ccp5 is the principal tubulin deglutamylase that maintains functional levels of cilia tubulin glutamylation. " 01/01/2021 - "We identify TTC30A/B as an essential node in the network of ciliary chondrodysplasia and nephronophthisis-like disease proteins and suggest that tubulin modifications and cilia segmentation contribute to skeletal and renal ciliopathy manifestations of ciliopathies in a cell type-specific manner. "
9.	Ubiquitin-Protein Ligases (Ubiquitin-Protein Ligase)IBA 03/21/2014 - "Although BBS11/TRIM32 represents a RING finger E3 ubiquitin ligase also involved in hereditary forms of muscular dystrophy, NPHP7/Glis2 is a Gli-like transcriptional repressor that localizes to the nucleus, deviating from the ciliary localization of most other ciliopathy-associated gene products. " 01/01/2022 - "Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers."
10.	Toll-Like Receptors (Toll-Like Receptor)IBA 01/01/2019 - "For instance, 5 among these novel proteins that are involved in cilia associated signaling pathways (like Notch, Wnt, Hedgehog, Toll-like receptor etc.) could be 'topologically important signaling proteins.' Therefore, based on this FOXJ1 network study we have predicted important effectors in the motile cilia interactome, which are possibly associated with ciliary biology and/or function and are likely to further our understanding of the pathophysiology in ciliopathies like PCD."

Therapies and Procedures

1.	Therapeutics 01/01/2019 - "Promising results from other organ systems imply the feasibility of biologics, with results from gene therapies proving to be a viable therapeutic option for ciliopathies and olfactory dysfunction." 05/15/2023 - "We also emphasize the signaling pathways involved in skeletal ciliopathies, which may assist in developing potential therapies for these diseases." 03/01/2023 - "It is expected that new mutations will be identified to characterize ciliopathies and promote new therapies." 01/01/2021 - "The development of gene-based therapies is opening up new avenues for the treatment of ciliopathies. " 01/01/2021 - "Currently, besides symptomatic therapy, there is no available therapeutic treatment option for olfactory dysfunction caused by ciliopathies. "
2.	Precision Medicine 01/01/2019 - "Our studies further indicated that ciliotherapy provides a possibility toward personalized medicine in ciliopathy patients." 01/01/2015 - "We believe that these cells can be used for further ex vivo study of ciliopathies and in the future, for personalized medicine."
3.	Liver Transplantation 01/01/2020 - "We describe seven individuals from seven families with syndromic ciliopathy clinical features, including severe neonatal cholestasis (lethal in one and necessitating liver transplant in two). " 11/01/2018 - "The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. " 01/01/2018 - "For this patient, evidence of liver dysfunction was evident from 2 months of age and progressed to frank cirrhosis and severe portal hypertension with multiple episodes of life-threatening variceal bleeding by age 6. This report illustrates the capability of orthotopic liver transplantation as a viable therapy for those pediatric patients suffering from severe liver failure secondary to a congenital ciliopathy, such as Sensenbrenner syndrome. "
4.	Kidney Transplantation 01/01/2020 - "The association of intracranial hypertension in a ciliopathy is a rare occurrence.  The aetiology of intracranial hypertension in this case is likely multi-factorial, due to renal transplantation, post-renal transplant medications and/ or weight gain.  With evidence of cilia involvement in the central nervous system, ciliary dysfunction may contribute to intracranial hypertension, and should be considered in these patients presenting with headaches. " 11/15/2009 - "While the majority of ADPKD, ARPKD, and NPHP patients require renal transplantation, the frequency and rate of progression to renal failure varies considerably in other ciliopathies. "
5.	Intravitreal Injections 01/01/2019 - "Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. "