ArticleAmerican journal of human genetics2006
Evidence that translation reinitiation leads to a partially functional Menkes protein containing two copper-binding sites.
Article in American journal of human genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Novel examples of NMD escape through alternative intronic polyadenylation.NAR genomics and bioinformatics · 2026Article
- The CDKL5 kinase undergoes liquid-liquid phase separation driven by a serine-rich C-terminal region.Life science alliance · 2026Article
- Phenotypic and mutational spectrum of 17 Chinese patients with Menkes Disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Observational
- Genetic etiology of progressive pediatric neurological disorders.Pediatric research · 2024Article
- Principles, mechanisms, and biological implications of translation termination-reinitiation.RNA (New York, N.Y.) · 2023Article
- Translation reinitiation after uORFs does not fully protect mRNAs from nonsense-mediated decay.RNA (New York, N.Y.) · 2023Article
- Premature Termination Codon in 5' Region of Desmoplakin and Plakoglobin Genes May Escape Nonsense-Mediated Decay through the Reinitiation of Translation.International journal of molecular sciences · 2022Article
- Menkes disease diagnosed by aTranslational pediatrics · 2021Article
- Article
- SRSF7 maintains its homeostasis through the expression of Split-ORFs and nuclear body assembly.Nature structural & molecular biology · 2020Article
- How to get away with nonsense: Mechanisms and consequences of escape from nonsense-mediated RNA decay.Wiley interdisciplinary reviews. RNA · 2020Review
- Review
- Nonsense mutation-dependent reinitiation of translation in mammalian cells.Nucleic acids research · 2019Article
- A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon.Human molecular genetics · 2018Article
- 13 novel putative mutations in ATP7A found in a cohort of 25 Italian families.Metabolic brain disease · 2017Article
- Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease.Scientific reports · 2017Article
- Illegitimate translation causes unexpected gene expression from on-target out-of-frame alleles created by CRISPR-Cas9.Scientific reports · 2016Article
- Metal-Dependent Regulation of ATP7A and ATP7B in Fibroblast Cultures.Frontiers in molecular neuroscience · 2016Article
- Mutations in the intellectual disability gene KDM5C reduce protein stability and demethylase activity.Human molecular genetics · 2015Article
- A novel two-nucleotide deletion in the ATP7A gene associated with delayed infantile onset of Menkes disease.Pediatric neurology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Menkes disease (MD) is an X-linked recessive disorder of copper metabolism. It is caused by mutations in the ATP7A gene encoding a copper-translocating P-type ATPase, which contains six N-terminal copper-binding sites (CBS1-CBS6). Most patients die in early childhood. We investigated the functional effect of a large frameshift deletion in ATP7A (including exons 3 and 4) identified in a patient with MD with unexpectedly mild symptoms and long survival. The mutated transcript, ATP7A(Delta ex3+ex4), contains a premature termination codon after 46 codons. Although such transcripts are generally degraded by nonsense-mediated mRNA decay (NMD), it was established by real-time PCR quantification that the ATP7A(Delta ex3+ex4) transcript was protected from degradation. A combination of in vitro translation, recombinant expression, and immunocytochemical analysis provided evidence that the ATP7A(Delta ex3+ex4) transcript was protected from degradation because of reinitiation of protein translation. Our findings suggest that reinitiation takes place at two downstream internal codons. The putative N-terminally truncated proteins contain only CBS5 and CBS6. Cellular localization and copper-dependent trafficking of the major part of endogenous and recombinant ATP7A(Delta ex3+ex4) proteins were similar to the wild-type ATP7A protein. Furthermore, the ATP7A(Delta ex3+ex4) cDNA was able to rescue a yeast strain lacking the homologous gene, CCC2. In summary, we propose that reinitiation of the NMD-resistant ATP7A(Delta ex3+ex4) transcript leads to the synthesis of N-terminally truncated and at-least-partially functional Menkes proteins missing CBS1-CBS4. This finding--that a mutation that would have been assumed to be null is not--highlights the need to examine the biochemical phenotype of patients to deduce the efficacy of copper therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.