ArticleHuman genetics2018
Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies).
Article in Human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 60 citations in OpenAlex.
- The NALCN channel complex is necessary for stabilizing sleep in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2026Article
- Reversible high-fat ketogenic formula-induced hypertriglyceridemia in a child with NALCN mutation on a ketogenic diet: a case report.Molecular biology reports · 2026Article
- Article
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- The sodium leak channel NALCN is regulated by neuronal SNARE complex proteins.Science advances · 2025Article
- Imbalance inInternational journal of molecular sciences · 2024Article
- Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore region.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The NaeLife · 2024Article
- Widening the infantile hypotonia with psychomotor retardation and characteristic Facies-1 Syndrome's clinical and molecular spectrum through NALCNFrontiers in genetics · 2024Article
- Case Report: New presentation of CLIFAHDD syndrome with a novel variant in the NALCN gene and a literature review.Frontiers in pediatrics · 2024Article
- The NabioRxiv : the preprint server for biology · 2023Article
- Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.Clinical genetics · 2023Article
- New presentation of CLIFAHDD syndrome with a novel variant inClinical case reports · 2023Article
- Network-Based Data Analysis Reveals Ion Channel-Related Gene Features in COVID-19: A Bioinformatic Approach.Biochemical genetics · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- NALCN is a potential biomarker and therapeutic target in human cancers.Frontiers in genetics · 2023Article
- Architecture of the human NALCN channelosome.Cell discovery · 2022Article
- Differential modulation of C. elegans motor behavior by NALCN and two-pore domain potassium channels.PLoS genetics · 2022Article
- Article
- Case Report: AFrontiers in pediatrics · 2022Article
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Authors and funding
45 authors at 18 institutions in 6 countries.
Funding
Abstract
NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the "NALCN channelosome", consisting of multiple proteins including UNC80 and UNC79. The predominant neuronal expression pattern and its function suggest an important role in neuronal function and disease. So far, biallelic NALCN and UNC80 variants have been described in a small number of individuals leading to infantile hypotonia, psychomotor retardation, and characteristic facies 1 (IHPRF1, OMIM 615419) and 2 (IHPRF2, OMIM 616801), respectively. Heterozygous de novo NALCN missense variants in the S5/S6 pore-forming segments lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD, OMIM 616266) with some clinical overlap. In this study, we present detailed clinical information of 16 novel individuals with biallelic NALCN variants, 1 individual with a heterozygous de novo NALCN missense variant and an interesting clinical phenotype without contractures, and 12 individuals with biallelic UNC80 variants. We report for the first time a missense NALCN variant located in the predicted S6 pore-forming unit inherited in an autosomal-recessive manner leading to mild IHPRF1. We show evidence of clinical variability, especially among IHPRF1-affected individuals, and discuss differences between the IHPRF1- and IHPRF2 phenotypes. In summary, we provide a comprehensive overview of IHPRF1 and IHPRF2 phenotypes based on the largest cohort of individuals reported so far and provide additional insights into the clinical phenotypes of these neurodevelopmental diseases to help improve counseling of affected families.
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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.