ArticleJournal of medical genetics2016
MKS1 regulates ciliary INPP5E levels in Joubert syndrome.
Article in Journal of medical genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis.The Journal of clinical investigation · 2026Article
- Regulation of INPP5E in Ciliogenesis, Development, and Disease.International journal of biological sciences · 2025Review
- Technologies, strategies, and cautions when deconvoluting genome-wide association signals: FTO in focus.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023Review
- Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies.Biomolecules · 2023Review
- Composition, organization and mechanisms of the transition zone, a gate for the cilium.EMBO reports · 2022Review
- Article
- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- Genotype-phenotype correlates in Joubert syndrome: A review.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Balancing the length of the distal tip by septins is key for stability and signalling function of primary cilia.The EMBO journal · 2022Article
- Systematic analysis of cilia characteristics and Hedgehog signaling in five immortal cell lines.PloS one · 2022Article
- Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations ofFrontiers in genetics · 2022Article
- Mild Clinical Presentation of Joubert Syndrome in a Male Adult Carrying BiallelicDiagnostics (Basel, Switzerland) · 2021Article
- Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone.Molecular biology of the cell · 2021Article
- Superresolution Microscopy Reveals Distinct Phosphoinositide Subdomains Within the Cilia Transition Zone.Frontiers in cell and developmental biology · 2021Article
- Signaling in the primary cilium through the lens of the Hedgehog pathway.Wiley interdisciplinary reviews. Developmental biology · 2020Review
- Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is essential as a diffusion barrier for ciliary membrane proteins.Molecular biology of the cell · 2020Article
- Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.The Journal of clinical investigation · 2020Article
- Genetics of syndromic ocular coloboma: CHARGE and COACH syndromes.Experimental eye research · 2020Review
- Novel Compound Heterozygous Variants inFrontiers in genetics · 2020Article
- The Enigmatic Role of Lipids in Cilia Signaling.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
27 authors at 13 institutions in 8 countries.
Funding
Abstract
backgroundJoubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation 'the molar tooth sign'. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel-Gruber syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS.
methodsWe measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a three-dimensional (3D) spheroid rescue assay to test the effects of disease-related MKS1 mutations.
resultsWe report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals with MKS1-related JS carry ≥ 1 non-truncating mutation. Fibroblasts from individuals with MKS1-related JS make normal or fewer cilia than control fibroblasts, their cilia are more variable in length than controls, and show decreased ciliary ARL13B and INPP5E. Additionally, MKS1 mutant alleles have similar effects in 3D spheroids.
conclusionsMKS1 functions in the transition zone at the base of the cilium to regulate ciliary INPP5E content, through an ARL13B-dependent mechanism. Mutations in INPP5E also cause JS, so our findings in patient fibroblasts support the notion that loss of INPP5E function, due to either mutation or mislocalisation, is a key mechanism underlying JS, downstream of MKS1 and ARL13B.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.