ArticleCell death & disease2020
Biallelic loss of function NEK3 mutations deacetylate α-tubulin and downregulate NUP205 that predispose individuals to cilia-related abnormal cardiac left-right patterning.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Broadening horizons: new links between cilia and heart development and disease.Frontiers in cardiovascular medicine · 2026Review
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- Systematic Exploration of Potential Druggable Genes for Ischemic Stroke Employing Genome-Wide Mendelian Randomization Analysis.Brain and behavior · 2025Article
- Tubulin Acetylation: A Critical Regulator of Microtubule Function.Results and problems in cell differentiation · 2025Review
- Advances in the understanding of nuclear pore complexes in human diseases.Journal of cancer research and clinical oncology · 2024Review
- Article
- Non-classical functions of nuclear pore proteins in ciliopathy.Frontiers in molecular biosciences · 2023Review
- Article
- LOF variants identifying candidate genes of laterality defects patients with congenital heart disease.PLoS genetics · 2022Article
- Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.Human genomics · 2022Article
- Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.Human genomics · 2022Article
- Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease.Human genetics · 2022Article
- The genetic landscape of cardiovascular left-right patterning defects.Current opinion in genetics & development · 2022Review
- Microscopic artificial cilia - a review.Lab on a chip · 2022Review
- Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice.Cell death & disease · 2022Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective left-right (LR) organization involving abnormalities in cilia ultrastructure causes laterality disorders including situs inversus (SI) and heterotaxy (Htx) with the prevalence approximately 1/10,000 births. In this study, we describe two unrelated family trios with abnormal cardiac LR patterning. Through whole-exome sequencing (WES), we identified compound heterozygous mutations (c.805-1G >C; p. Ile269GlnfsTer8/c.1117dupA; p.Thr373AsnfsTer19) (c.29T>C; p.Ile10Thr/c.356A>G; p.His119Arg) of NEK3, encoding a NIMA (never in mitosis A)-related kinase, in two affected individuals, respectively. Protein levels of NEK3 were abrogated in Patient-1 with biallelic loss-of function (LoF) NEK3 mutations that causes premature stop codon. Subsequence transcriptome analysis revealed that NNMT (nicotinamide N-methyltransferase) and SIRT2 (sirtuin2) was upregulated by NEK3 knockdown in human retinal pigment epithelial (RPE) cells in vitro, which associates α-tubulin deacetylation by western blot and immunofluorescence. Transmission electron microscopy (TEM) analysis further identified defective ciliary ultrastructure in Patient-1. Furthermore, inner ring components of nuclear pore complex (NPC) including nucleoporin (NUP)205, NUP188, and NUP155 were significantly downregulated in NEK3-silenced cells. In conclusion, we identified biallelic mutations of NEK3 predispose individual to abnormal cardiac left-right patterning via SIRT2-mediated α-tubulin deacetylation and downregulation of inner ring nucleoporins. Our study suggested that NEK3 could be a candidate gene for human ciliopathies.
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