ArticleJCI insight2023
Loss-of-function variant in SPIN4 causes an X-linked overgrowth syndrome.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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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.
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.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- "Quiescence" in the resting zone of the growth plate: a systematic review.Stem cells (Dayton, Ohio) · 2026Pooled it
- Chromosome X-wide association study in case control studies of pathologically confirmed Alzheimer's disease in a European population.Translational psychiatry · 2024Pooled it
- Human papillomavirus16 E7 enhances cell stemness by regulating the APC2/SPIN4/β-catenin axis in cervical cancer.Oncogenesis · 2026Article
- Effects of Spin4 ablation in aging mice: body composition, bone density, and malignancy prevalence.bioRxiv : the preprint server for biology · 2026Article
- Article
- Clinical Observation of a Rare Binder Phenotype With Fetal Overgrowth Due to aMaternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2025Article
- The genetic basis of human height.Nature reviews. Genetics · 2025Review
- Simultaneous Effects of Single-Nucleotide Polymorphisms on the Estimated Breeding Value of Milk, Fat, and Protein Yield of Holstein Friesian Cows in Hungary.Animals : an open access journal from MDPI · 2024Article
- Epigenetic Causes of Overgrowth Syndromes.The Journal of clinical endocrinology and metabolism · 2024Review
- Growth disorders caused by variants in epigenetic regulators: progress and prospects.Frontiers in endocrinology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Overgrowth syndromes can be caused by pathogenic genetic variants in epigenetic writers, such as DNA and histone methyltransferases. However, no overgrowth disorder has previously been ascribed to variants in a gene that acts primarily as an epigenetic reader. Here, we studied a male individual with generalized overgrowth of prenatal onset. Exome sequencing identified a hemizygous frameshift variant in Spindlin 4 (SPIN4), with X-linked inheritance. We found evidence that SPIN4 binds specific histone modifications, promotes canonical WNT signaling, and inhibits cell proliferation in vitro and that the identified frameshift variant had lost all of these functions. Ablation of Spin4 in mice recapitulated the human phenotype with generalized overgrowth, including increased longitudinal bone growth. Growth plate analysis revealed increased cell proliferation in the proliferative zone and an increased number of progenitor chondrocytes in the resting zone. We also found evidence of decreased canonical Wnt signaling in growth plate chondrocytes, providing a potential explanation for the increased number of resting zone chondrocytes. Taken together, our findings provide strong evidence that SPIN4 is an epigenetic reader that negatively regulates mammalian body growth and that loss of SPIN4 causes an overgrowth syndrome in humans, expanding our knowledge of the epigenetic regulation of human growth.
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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.