ArticleAnnals of neurology2018
KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy-lysosome defect.
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
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- Carrier screening in the reproductive setting-Are there medical implications for the heterozygote?-A guide for clinicians.Pregnancy (Hoboken, N.J.) · 2026Review
- Identification of common variants influencing risk of the three-repeat tauopathy Pick's disease: a genome wide association study.medRxiv : the preprint server for health sciences · 2025Article
- Impact of rapid genomic testing on clinical outcomes of acutely unwell children presenting with severe epilepsy.European journal of human genetics : EJHG · 2025Article
- Bi-allelic KCTD19 variants associated with meiotic arrest and non-obstructive azoospermia in humans.Journal of human genetics · 2025Article
- The Whi2-Psr1-Psr2 complex selectively regulates TORC1 and autophagy under low leucine conditions but not nitrogen depletion.Autophagy · 2025Article
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- Case Report: Compound heterozygous KCTD7 variants in two siblings presenting with myoclonic epilepsy and ataxia.Frontiers in neuroscience · 2025Article
- A novel pathogenic variant in the KCTD7 gene in a patient with neuronal ceroid lipofuscinosis (CLN14): a case report and review of the literature.BMC neurology · 2024Review
- KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- KCTD15 acts as an anti-tumor factor in colorectal cancer cells downstream of the demethylase FTO and the m6A reader YTHDF2.Communications biology · 2024Article
- A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3.International journal of molecular sciences · 2024Article
- RNA sequencing of peripheral blood in amyotrophic lateral sclerosis reveals distinct molecular subtypes: Considerations for biomarker discovery.Neuropathology and applied neurobiology · 2023Article
- Loss-of-function variants iniScience · 2023Article
- KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility.Cell death and differentiation · 2023Article
- Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.Cell discovery · 2023Article
- Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family.International journal of molecular sciences · 2022Article
- KCTD9 inhibits the Wnt/β-catenin pathway by decreasing the level of β-catenin in colorectal cancer.Cell death & disease · 2022Article
- Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects.Disease models & mechanisms · 2022Article
- KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses.Science advances · 2022Article
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Authors and funding
43 authors at 20 institutions in 8 countries.
Funding
Abstract
objectiveSeveral small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function.
methodsNovel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell-based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples.
resultsPatients with KCTD7 mutations can exhibit movement disorders or developmental regression before seizure onset, and are distinguished from similar disorders by an earlier age of onset. Although most published KCTD7 patient variants were excluded from a genome sequence database of normal human variations, most newly identified patient variants are present in this database, potentially challenging disease causality. However, genetic analysis and impaired biochemical interactions with cullin 3 support a causal role for patient KCTD7 variants, suggesting deleterious alleles of KCTD7 and other rare disease variants may be underestimated. Both patient-derived fibroblasts and yeast lacking Whi2 with sequence similarity to KCTD7 have impaired autophagy consistent with brain pathology.
interpretationBiallelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders. KCTD7 deficiency appears to cause an underlying autophagy-lysosome defect conserved in yeast, thereby assigning a biological role for KCTD7. Ann Neurol 2018;84:774-788.
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