ArticleAmerican journal of human genetics2019
Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 1 of them a synthesis that pooled it.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Pooled it
- The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.Developmental cell · 2026Article
- Microautophagy: current understanding of its molecular mechanisms and functions.Autophagy reports · 2026Review
- Lysosomal and mTORC1 signaling dysregulation underpin the pathology of spastic paraplegia type 80.Nature communications · 2025Article
- 4-Phenylbutyric Acid Improves Gait Ability of UBAP1-Related Spastic Paraplegia Mouse Model: Therapeutic Potential for SPG80.International journal of molecular sciences · 2025Article
- Cell biological insights into human STING variants.Cell structure and function · 2025Review
- ESCRT-I and PTPN23 mediate microautophagy of ubiquitylated tau aggregates.The Journal of cell biology · 2025Article
- Review
- A quantitative method to monitor STING degradation with dual-luciferase reporters.Cell structure and function · 2025Article
- Article
- Article
- Loss of HD-PTP function results in lipodystrophy, defective cellular signaling and altered lipid homeostasis.Journal of cell science · 2024Article
- Novel genetic variant in hereditary spastic paraparesis.BMJ case reports · 2024Article
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
- TOPORS as a novel causal gene for Joubert syndrome.American journal of medical genetics. Part A · 2023Article
- Deep structured learning for variant prioritization in Mendelian diseases.Nature communications · 2023Article
- Aberrant Cyclin D1 splicing in cancer: from molecular mechanism to therapeutic modulation.Cell death & disease · 2023Review
- ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling.Nature communications · 2023Article
- Ubap1 knock-in mice reproduced the phenotype of SPG80.Journal of human genetics · 2022Article
- Hereditary Spastic Paraplegia: An Update.International journal of molecular sciences · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
42 authors at 14 institutions in 8 countries.
Funding
Abstract
The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology.
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.