ArticleNature neuroscience2015
A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.
Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
76 citing papers in PubMed, 126 citations in OpenAlex.
- ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- DNA Methylation Status of Regulatory Regions of Apoptosis-Associated Genes in Dystropy «Huntington's Disease-Non-Small Cell Lung Cancer».Epigenomes · 2025Article
- Fueling neurodegeneration: metabolic insights into microglia functions.Journal of neuroinflammation · 2024Review
- Regulation ofInternational journal of molecular sciences · 2024Review
- Stereopure ASOs: An unanticipated increase in selectivity for targeting mutant HTT.Molecular therapy. Nucleic acids · 2024Article
- Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutantMolecular therapy. Nucleic acids · 2024Article
- The regulating effect of curcumin on NF-κB pathway in neurodegenerative diseases: a review of the underlying mechanisms.Inflammopharmacology · 2024Review
- A programmable dual-targeting siRNA scaffold supports potent two-gene modulation in the central nervous system.Nucleic acids research · 2024Article
- Review
- Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions.Journal of Huntington's disease · 2024Article
- Ascertainment of uninterrupted CAG repeat length and disease-modifying variants in fragment-based genetic testing for Huntington Disease.Genetics in medicine open · 2024Article
- Epigenetic editing for autosomal dominant neurological disorders.Frontiers in genome editing · 2024Review
- Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity.PloS one · 2024Article
- A programmable dual-targeting di-valent siRNA scaffold supports potent multi-gene modulation in the central nervous system.bioRxiv : the preprint server for biology · 2023Article
- Combined RNA interference and gene replacement therapy targeting MFN2 as proof of principle for the treatment of Charcot-Marie-Tooth type 2A.Cellular and molecular life sciences : CMLS · 2023Article
- Genetic topography and cortical cell loss in Huntington's disease link development and neurodegeneration.Brain : a journal of neurology · 2023Article
- Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis.Nature chemical biology · 2023Article
- IKBKB reduces huntingtin aggregation by phosphorylating serine 13 via a non-canonical IKK pathway.Life science alliance · 2023Article
- Loss of CAA interruption and intergenerational CAG instability in Chinese patients with Huntington's disease.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Identification of quantitative trait loci and candidate genes for seed folate content in soybean.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 4 institutions in 5 countries.
Funding
Abstract
Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.
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Registered trials
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.