ArticleNature communications2022
A neomorphic variant in SP7 alters sequence specificity and causes a high-turnover bone disorder.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 38 citations in OpenAlex.
- Pathogenesis and precision management of osteogenesis imperfecta: from genetic mechanisms to novel therapies.World journal of pediatrics : WJP · 2026Review
- Histone arginine demethylase JMJD7 promotes bone formation through regulating α-Ketoglutarate metabolism.Cell death and differentiation · 2026Article
- microRNA Expression in the Late Embryonic Pax6-Null Mouse Cerebellum.Molecular neurobiology · 2025Article
- Genomic structural equation modeling uncovers novel risk loci for bone metabolic disorders: cross-tissue genetic mechanisms and bone-brain axis regulation.BMC musculoskeletal disorders · 2025Article
- RING-Box E3 Ligase Target N-Terminal Lysine 55 to Regulate Turnover of Sp7 Protein.Journal of cellular biochemistry · 2025Article
- Osteoclast-independent osteocyte dendrite defects in mice bearing the osteogenesis imperfecta-causing Sp7 R342C mutation.Bone research · 2025Article
- Molecular crosstalk in SP7-mediated osteogenesis: Regulatory mechanisms and therapeutic potential.Osteoporosis and sarcopenia · 2025Review
- SP7 transcription factor ameliorates bone defect healing in low-density lipoprotein receptor-related protein 5 (LRP5)-dependent osteoporosis mice.Journal of Zhejiang University. Science. B · 2025Article
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Article
- Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.International journal of molecular sciences · 2024Review
- A homozygousJBMR plus · 2024Article
- Article
- Bone Material Properties in Bone Diseases Affecting Children.Current osteoporosis reports · 2023Review
- MiR-224-5p inhibits osteoblast differentiation and impairs bone formation by targeting Runx2 and Sp7.Cytotechnology · 2023Article
- Transcriptional reprogramming by mutated IRF4 in lymphoma.Nature communications · 2023Article
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Article
- Classification of osteogenesis imperfecta: Importance for prophylaxis and genetic counseling.World journal of clinical cases · 2023Review
- SP7: from Bone Development to Skeletal Disease.Current osteoporosis reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
SP7/Osterix is a transcription factor critical for osteoblast maturation and bone formation. Homozygous loss-of-function mutations in SP7 cause osteogenesis imperfecta type XII, but neomorphic (gain-of-new-function) mutations of SP7 have not been reported in humans. Here we describe a de novo dominant neomorphic missense variant (c.926 C > G:p.S309W) in SP7 in a patient with craniosynostosis, cranial hyperostosis, and long bone fragility. Histomorphometry shows increased osteoblasts but decreased bone mineralization. Mice with the corresponding variant also show a complex skeletal phenotype distinct from that of Sp7-null mice. The mutation alters the binding specificity of SP7 from AT-rich motifs to a GC-consensus sequence (typical of other SP family members) and produces an aberrant gene expression profile, including increased expression of Col1a1 and endogenous Sp7, but decreased expression of genes involved in matrix mineralization. Our study identifies a pathogenic mechanism in which a mutation in a transcription factor shifts DNA binding specificity and provides important in vivo evidence that the affinity of SP7 for AT-rich motifs, unique among SP proteins, is critical for normal osteoblast differentiation.
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.