ArticleAmerican journal of human genetics2011
Exome sequencing and cis-regulatory mapping identify mutations in MAK, a gene encoding a regulator of ciliary length, as a cause of retinitis pigmentosa.
Article in American journal of human genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 116 citations in OpenAlex.
- Ciliary Defects in Inherited Retinal Diseases.Advanced genetics (Hoboken, N.J.) · 2026Review
- Post-Translational Modifications in Cilia and Ciliopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Article
- Kinase-dependent regulation of ciliary protein transport and its implications for therapy.Frontiers in molecular biosciences · 2025Review
- Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival.Life science alliance · 2024Article
- Male germ cell-associated kinase is required for axoneme formation during ciliogenesis in zebrafish photoreceptors.Disease models & mechanisms · 2024Article
- Neurons dispose of hyperactive kinesin into glial cells for clearance.The EMBO journal · 2024Article
- The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases.iScience · 2024Article
- Bridging the gap of vision restoration.Frontiers in cellular neuroscience · 2024Review
- CMGC Kinases in Health and Cancer.Cancers · 2023Review
- The flagellar length control system: exploring the physical biology of organelle size.Physical biology · 2023Review
- DYF-5/MAK-dependent phosphorylation promotes ciliary tubulin unloading.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genetic dissection of non-syndromic retinitis pigmentosa.Indian journal of ophthalmology · 2022Review
- Article
- Novel eye genes systematically discovered through an integrated analysis of mouse transcriptomes and phenome.Computational and structural biotechnology journal · 2020Article
- Ciliogenesis associated kinase 1: targets and functions in various organ systems.FEBS letters · 2019Review
- The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies.Acta ophthalmologica · 2019Article
- MetaDome: Pathogenicity analysis of genetic variants through aggregation of homologous human protein domains.Human mutation · 2019Article
- LF4/MOK and a CDK-related kinase regulate the number and length of cilia in Tetrahymena.PLoS genetics · 2019Article
- Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes.Genes · 2018Article
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
A fundamental challenge in analyzing exome-sequence data is distinguishing pathogenic mutations from background polymorphisms. To address this problem in the context of a genetically heterogeneous disease, retinitis pigmentosa (RP), we devised a candidate-gene prioritization strategy called cis-regulatory mapping that utilizes ChIP-seq data for the photoreceptor transcription factor CRX to rank candidate genes. Exome sequencing combined with this approach identified a homozygous nonsense mutation in male germ cell-associated kinase (MAK) in the single affected member of a consanguineous Turkish family with RP. MAK encodes a cilium-associated mitogen-activated protein kinase whose function is conserved from the ciliated alga, Chlamydomonas reinhardtii, to humans. Mutations in MAK orthologs in mice and other model organisms result in abnormally long cilia and, in mice, rapid photoreceptor degeneration. Subsequent sequence analyses of additional individuals with RP identified five probands with missense mutations in MAK. Two of these mutations alter amino acids that are conserved in all known kinases, and an in vitro kinase assay indicates that these mutations result in a loss of kinase activity. Thus, kinase activity appears to be critical for MAK function in humans. This study highlights a previously underappreciated role for CRX as a direct transcriptional regulator of ciliary genes in photoreceptors. In addition, it demonstrates the effectiveness of CRX-based cis-regulatory mapping in prioritizing candidate genes from exome data and suggests that this strategy should be generally applicable to a range of retinal diseases.
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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.