ArticleHuman molecular genetics2009
Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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
66 citing papers in PubMed, 139 citations in OpenAlex.
- Variant-specific RNA testing resolves variants of uncertain significance in exome testing.BMC genomics · 2026Article
- Abnormal von Willebrand factor multimer pattern withoutBlood vessels, thrombosis & hemostasis · 2026Article
- Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol.Nature communications · 2025Article
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- Roles for the long non-coding RNAiScience · 2025Article
- Golgi pH elevation due to loss of V-ATPase subunit V0a2 function correlates with tissue-specific glycosylation changes and globozoospermia.Cellular and molecular life sciences : CMLS · 2024Article
- Golgi pH homeostasis stabilizes the lysosomal membrane throughLife science alliance · 2024Article
- Elastogenesis in Focus: Navigating Elastic Fibers Synthesis for Advanced Dermal Biomaterial Formulation.Advanced healthcare materials · 2024Review
- Identification of a novel intronic variant of ATP6V0A2 in a Han-Chinese family with cutis laxa.Molecular biology reports · 2024Article
- Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function.American journal of physiology. Endocrinology and metabolism · 2024Article
- The Human Mutation K237_V238del in a Putative Lipid Binding Motif within the V-ATPase a2 Isoform Suggests a Molecular Mechanism Underlying Cutis Laxa.International journal of molecular sciences · 2024Article
- A novel deletion mutation in the ATP6V0A2 gene in an Iranian patient affected by autosomal recessive cutis laxa.Irish journal of medical science · 2023Article
- Extracellular matrix in skin diseases: The road to new therapies.Journal of advanced research · 2023Review
- Role of elastic fiber degradation in disease pathogenesis.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Structural and functional understanding of disease-associated mutations in V-ATPase subunit a1 and other isoforms.Frontiers in molecular neuroscience · 2023Review
- The cytosolic N-terminal domain of V-ATPase a-subunits is a regulatory hub targeted by multiple signals.Frontiers in molecular biosciences · 2023Review
- Supply chain logistics - the role of the Golgi complex in extracellular matrix production and maintenance.Journal of cell science · 2022Review
- Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5.Nature communications · 2021Article
- The Golgi as a "Proton Sink" in Cancer.Frontiers in cell and developmental biology · 2021Article
6 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
26 authors at 16 institutions in 11 countries.
Funding
Abstract
Autosomal recessive cutis laxa type 2 (ARCL2), a syndrome of growth and developmental delay and redundant, inelastic skin, is caused by mutations in the a2 subunit of the vesicular ATPase H+-pump (ATP6V0A2). The goal of this study was to define the disease mechanisms that lead to connective tissue lesions in ARCL2. In a new cohort of 17 patients, DNA sequencing of ATP6V0A2 detected either homozygous or compound heterozygous mutations. Considerable allelic and phenotypic heterogeneity was observed, with a missense mutation of a moderately conserved residue p.P87L leading to unusually mild disease. Abnormal N- and/or mucin type O-glycosylation was observed in all patients tested. Premature stop codon mutations led to decreased ATP6V0A2 mRNA levels by destabilizing the mutant mRNA via the nonsense-mediated decay pathway. Loss of ATP6V0A2 either by siRNA knockdown or in ARCL2 cells resulted in distended Golgi cisternae, accumulation of abnormal lysosomes and multivesicular bodies. Immunostaining of ARCL2 cells showed the accumulation of tropoelastin (TE) in the Golgi and in large, abnormal intracellular and extracellular aggregates. Pulse-chase studies confirmed impaired secretion and increased intracellular retention of TE, and insoluble elastin assays showed significantly reduced extracellular deposition of mature elastin. Fibrillin-1 microfibril assembly and secreted lysyl oxidase activity were normal in ARCL2 cells. TUNEL staining demonstrated increased rates of apoptosis in ARCL2 cell cultures. We conclude that loss-of-function mutations in ATP6V0A2 lead to TE aggregation in the Golgi, impaired clearance of TE aggregates and increased apoptosis of elastogenic cells.
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.