ArticleBrain : a journal of neurology2018
Biallelic UFM1 and UFC1 mutations expand the essential role of ufmylation in brain development.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 114 citations in OpenAlex.
- Ufl1-Mediated UFMylation Sustains Amelogenesis by Stabilizing RUNX2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- Rare Genetic Diseases with Founder Effect in Roma Children.Life (Basel, Switzerland) · 2026Article
- A severe neurodevelopmental syndrome linked to a South Asian founder variant in the UFMylation adaptor CDK5RAP3.Acta neuropathologica · 2026Article
- Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and function.EMBO molecular medicine · 2026Article
- Diagnostic Yield of Comprehensive Reanalysis After Nondiagnostic Short-Read Genome Sequencing in Infants With Unexplained Epilepsy.Neurology · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- UFMylation in lipid metabolism disorders-associated diseases.Molecular biology reports · 2026Review
- UFM1 regulates ferroptosis in oral squamous cell carcinoma by stabilizing SLC7A11.American journal of cancer research · 2026Article
- Post-translational modifications as a regulatory code for tau function in health and disease.Frontiers in dementia · 2026Review
- UFM1 at the endoplasmic reticulum: linking ER stress, ribosome quality control, and ER-phagy.Essays in biochemistry · 2025Review
- MCM5 UFMylation regulates replication origin firing and fork progression.The EMBO journal · 2025Article
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- UFMylation: A supervisor of the HIF1α pathway and a potential therapeutic target for anti-PD-1 combination therapy in hypoxic tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Studies on the functional role of UFMylation in cells (Review).Molecular medicine reports · 2025Review
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- UFC1 reveals the multifactorial and plastic nature of oxyanion holes in E2 conjugating enzymes.Nature communications · 2025Article
- Neuronal CDK5RAP3 deficiency leads to encephalo-dysplasia via upregulation of N-glycosylases and glycogen deposition.Cell death discovery · 2025Article
- Multifaceted roles of UFMylation in health and disease.Acta pharmacologica Sinica · 2025Review
- Hypomyelinating Leukodystrophy 14 (HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype Reversable with Hesperetin.Medicines (Basel, Switzerland) · 2025Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 12 institutions in 4 countries.
Funding
Abstract
The post-translational modification of proteins through the addition of UFM1, also known as ufmylation, plays a critical developmental role as revealed by studies in animal models. The recent finding that biallelic mutations in UBA5 (the E1-like enzyme for ufmylation) cause severe early-onset encephalopathy with progressive microcephaly implicates ufmylation in human brain development. More recently, a homozygous UFM1 variant was proposed as a candidate aetiology of severe early-onset encephalopathy with progressive microcephaly. Here, we establish a locus for severe early-onset encephalopathy with progressive microcephaly based on two families, and map the phenotype to a novel homozygous UFM1 mutation. This mutation has a significantly diminished capacity to form thioester intermediates with UBA5 and with UFC1 (the E2-like enzyme for ufmylation), with resulting impaired ufmylation of cellular proteins. Remarkably, in four additional families where eight children have severe early-onset encephalopathy with progressive microcephaly, we identified two biallelic UFC1 mutations, which impair UFM1-UFC1 intermediate formation with resulting widespread reduction of cellular ufmylation, a pattern similar to that observed with UFM1 mutation. The striking resemblance between UFM1- and UFC1-related clinical phenotype and biochemical derangements strongly argues for an essential role for ufmylation in human brain development. The hypomorphic nature of UFM1 and UFC1 mutations and the conspicuous depletion of biallelic null mutations in the components of this pathway in human genome databases suggest that it is necessary for embryonic survival, which is consistent with the embryonic lethal nature of knockout models for the orthologous genes.
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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.