The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy
Open accessAbstract
The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBA5, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBA5 variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.Ala371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg55His, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.Ala371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufm1 in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.Ala371Thr variant in trans with a loss-of-function allele in UBA5 underlies a severe infantile-onset encephalopathy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Citations
Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,508
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587
Self-citationAn integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711
Self-citationVan der Auwera, G. A., Carneiro, M. O., Hartl, C., Poplin, R., del Angel, G., Levy‐Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. (2013) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1110s43 · Cited by 6,687
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841
Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor
McLaren, W. M., Yates, B., Ríos, D., Chen, Y., Flicek, P., & Cunningham, F. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq330 · Cited by 1,586
GeneMatcher: a matching tool for connecting investigators with an interest in the same gene.
Sobreira, N., Schiettecatte, F., Valle, D., & Hamosh, A. (2015) · Human Mutation · doi:10.1002/humu.22844 · Cited by 1,529
Large-scale discovery of novel genetic causes of developmental disorders
Study, T. D. D. D. (2015) · Nature · doi:10.1038/nature14135 · Cited by 1,124
Cited by
Sorted by citations
Ribosomal protein RPL26 is the principal target of UFMylation
Walczak, C. P., Leto, D. E., Zhang, L., Riepe, C., Muller, R. Y., DaRosa, P. A., Ingolia, N. T., Elias, J. E., & Kopito, R. R. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1816202116 · Cited by 210
Wang, L., Xu, Y., Rogers, H. M., Saidi, L. F., Noguchi, C. T., Li, H., Yewdell, J. W., Guydosh, N. R., & Ye, Y. (2019) · Cell Research · doi:10.1038/s41422-019-0236-6 · Cited by 184
NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Marmiesse, A. F., Gouveia, S., & Couce, M. L. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170718101946 · Cited by 188
The UFMylation System in Proteostasis and Beyond
Gerakis, Y., Quintero, M. K., Li, H., & Hetz, C. A. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.09.005 · Cited by 165
PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth
Morita, M., Sato, T., Nomura, M., Sakamoto, Y., Inoue, Y., Tanaka, R., Ito, S., Kurosawa, K., Yamaguchi, K., Sugiura, Y., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.004 · Cited by 170
Self-citationDevelopmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 158
Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR
Zhu, H., Bhatt, B., Sivaprakasam, S., Cai, Y., Liu, S. M., Kodeboyina, S. K., Patel, N., Savage, N. M., Sharma, A. K., Kaufman, R. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08908-5 · Cited by 114
Yurchenko, A. A., Deniskova, T. E., Yudin, N. S., Dotsev, A. V., Хамируев, Т. Н., Selionova, M. I., Egorov, S. V., Reyer, H., Wimmers, K., Brem, G., et al. (2019) · BMC Genomics · doi:10.1186/s12864-019-5537-0 · Cited by 111
Li, J., Yue, G., Ma, W., Zhang, A., Zou, J., Cai, Y., Tang, X., Wang, J., Liu, J., Li, H., et al. (2018) · Circulation Heart Failure · doi:10.1161/circheartfailure.118.004917 · Cited by 103
The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3
Ishimura, R., El‐Gowily, A. H., Noshiro, D., Komatsu‐Hirota, S., Ono, Y., Shindo, M., Hatta, T., Abe, M., Uemura, T., Lee, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35501-0 · Cited by 104
Self-citationUFMylation: a ubiquitin-like modification
Zhou, X., Mahdizadeh, S. J., Gallo, M. L., Eriksson, L. A., Chevet, É., & Lafont, É. (2023) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2023.10.004 · Cited by 86
Recent advances in epilepsy genomics and genetic testing
Hebbar, M., & Mefford, H. C. (2020) · F1000Research · doi:10.12688/f1000research.21366.1 · Cited by 84
Cai, Y., Zhu, G., Liu, S. M., Pan, Z., Quintero, M. K., Poole, C. J., Lu, C., Zhu, H., Islam, B. N., van Riggelen, J., et al. (2019) · Cell Discovery · doi:10.1038/s41421-018-0070-x · Cited by 83
CDK5RAP3, a UFL1 substrate adaptor, is critical for liver development
Yang, R., Wang, H., Kang, B., Chen, B., Shi, Y., Yang, S., Sun, L., Liu, Y., Xiao, W., Zhang, T., et al. (2019) · Development · doi:10.1242/dev.169235 · Cited by 77
A guide to UFMylation, an emerging posttranslational modification
Millrine, D., Peter, J. J., & Kulathu, Y. (2023) · FEBS Journal · doi:10.1111/febs.16730 · Cited by 78
Papuc, S. M., Abela, L., Steindl, K., Begemann, A., Simmons, T. L., Schmitt, B., Zweier, M., Oneda, B., Socher, E., Crowther, L. M., et al. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-018-0299-8 · Cited by 72
The UFM1 system: Working principles, cellular functions, and pathophysiology
Komatsu, M., Inada, T., & Noda, N. N. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.11.034 · Cited by 73
Self-citationHuman UFSP1 is an active protease that regulates UFM1 maturation and UFMylation
Millrine, D., Cummings, T., Matthews, S. P., Peter, J. J., Magnussen, H. M., Lange, S. M., Macartney, T., Lamoliatte, F., Knebel, A., & Kulathu, Y. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111168 · Cited by 71
Decrypting UFMylation: How Proteins Are Modified with UFM1
Banerjee, S., Kumar, M., & Wiener, R. (2020) · Biomolecules · doi:10.3390/biom10101442 · Cited by 68
A 2020 View on the Genetics of Developmental and Epileptic Encephalopathies
Happ, H. C., & Carvill, G. L. (2020) · Epiliepsy currents/Epilepsy currents · doi:10.1177/1535759720906118 · Cited by 67
The expanding spectrum of movement disorders in genetic epilepsies
Papandreou, A., Danti, F. R., Spaull, R., Leuzzi, V., McTague, A., & Kurian, M. A. (2019) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14407 · Cited by 65
UFM1 founder mutation in the Roma population causes recessive variant of H-ABC
Hamilton, E. M. C., Bertini, E., Kalaydjieva, L. V., Morar, B., Dojčáková, D., Liu, J. S.-H., Vanderver, A. L., Curiel, J., Persoon, C. M., Diodato, D., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004578 · Cited by 62
Huber, J., Obata, M., Gruber, J., Akutsu, M., Löhr, F., Rogova, N. Y., Güntert, P., Đikić, I., Kirkin, V., Komatsu, M., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1606637 · Cited by 54
Self-citationUFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages
Balce, D. R., Wang, Y., McAllaster, M. R., Dunlap, B. F., Orvedahl, A., Hykes, B. L., Droit, L., Handley, S. A., Wilen, C. B., Doench, J. G., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2011763118 · Cited by 58
Structural basis for UFM1 transfer from UBA5 to UFC1
Kumar, M., Padala, P., Fahoum, J., Hassouna, F., Tsaban, T., Zoltsman, G., Banerjee, S., Cohen‐Kfir, E., Dessau, M. A., Rosenzweig, R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25994-6 · Cited by 55
Ishimura, R., Ito, S., Mao, G., Komatsu‐Hirota, S., Inada, T., Noda, N. N., & Komatsu, M. (2023) · Science Advances · doi:10.1126/sciadv.adh3635 · Cited by 53
Self-citationEbstein, F., Küry, S., Papendorf, J. J., & Krüger, E. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.733012 · Cited by 53
Mignon‐Ravix, C., Milh, M., Kaiser, C. S., Daniel, J., Riccardi, F., Cacciagli, P., Nagara, M., Busa, T., Liebau, E., & Villard, L. (2018) · Human Mutation · doi:10.1002/humu.23534 · Cited by 50
Compound heterozygous mutations in UBA5 causing early-onset epileptic encephalopathy in two sisters
Arnadottir, G. A., Jensson, B. Ö., Marelsson, S., Sulem, G., Oddsson, Á., Kristjansson, R. P., Benónísdóttir, S., Gudjonsson, S. A., Másson, G., Þórisson, G. Á., et al. (2017) · BMC Medical Genetics · doi:10.1186/s12881-017-0466-8 · Cited by 48
Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice
Tumiene, B., Maver, A., Writzl, K., Hodžić, A., Čuturilo, G., Kuzmanić-Šamija, R., Čulić, V., & Peterlin, B. (2017) · Clinical Genetics · doi:10.1111/cge.13203 · Cited by 47
Soudah, N., Padala, P., Hassouna, F., Kumar, M., Mashahreh, B., Lebedev, A. A., Isupov, M. N., Cohen‐Kfir, E., & Wiener, R. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.10.007 · Cited by 46
A novel approach to assess the ubiquitin‐fold modifier 1‐system in cells
Ishimura, R., Obata, M., Kageyama, S., Daniel, J., Tanaka, K., & Komatsu, M. (2016) · FEBS Letters · doi:10.1002/1873-3468.12518 · Cited by 40
Self-citationUfmylation reconciles salt stress-induced unfolded protein responses via ER-phagy in Arabidopsis
Li, B., Niu, F., Zeng, Y., Tse, M. K., Deng, C., Hong, L., Gao, S., Lo, S. W., Cao, W., Huang, S., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2208351120 · Cited by 38
Ni, M., Afroze, B., Xing, C., Pan, C., Shao, Y., Cai, L., Cantarel, B. L., Pei, J., Grishin, N. V., Hewson, S., et al. (2021) · Genetics in Medicine · doi:10.1038/s41436-020-01071-z · Cited by 37
A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy
Cabrera‐Serrano, M., Coote, D., Azmanov, D. N., Goullée, H., Andersen, E., McLean, C., Davis, M. R., Ishimura, R., Stark, Z., Vallat, J., et al. (2020) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2019-106496 · Cited by 36
Self-citationWang, L., Xu, Y., Yun, S., Yuan, Q., Satpute-Krishnan, P., & Ye, Y. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112028 · Cited by 34
Highly Specialized Ubiquitin-Like Modifications: Shedding Light into the UFM1 Enigma
Witting, K. F., & Mulder, M. P. C. (2021) · Biomolecules · doi:10.3390/biom11020255 · Cited by 33
Briere, L. C., Walker, M. A., High, F. A., Cooper, C. A., Rogers, C. A., Callahan, C. J., Ishimura, R., Ichimura, Y., Caruso, P. A., Sharma, N., et al. (2021) · Molecular Case Studies · doi:10.1101/mcs.a005827 · Cited by 32
Self-citationRARS1‐related hypomyelinating leukodystrophy: Expanding the spectrum
Mendes, M. I. S., Green, L. M. C., Bertini, E., Tonduti, D., Aiello, C., Smith, D. E. C., Salsano, E., Beerepoot, S., Hertecant, J., von Spiczak, S., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50960 · Cited by 31
Zhou, Y., Ye, X., Zhang, C., Wang, J., Guan, Z., Yan, J., Xu, L., Wang, K., Guan, D., Liang, Q., et al. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.04.006 · Cited by 29
UFMylation System: An Emerging Player in Tumorigenesis
Jing, Y., Mao, Z., & Chen, F. (2022) · Cancers · doi:10.3390/cancers14143501 · Cited by 27
The Post-Translational Role of UFMylation in Physiology and Disease
Wang, X., Xu, X., & Wang, Z. (2023) · Cells · doi:10.3390/cells12212543 · Cited by 29
Low, K. J., Baptista, J., Babiker, M. O. E., Caswell, R. C., King, C., Ellard, S., & Scurr, I. J. (2018) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2018.06.009 · Cited by 28
Deficiency of Murine UFM1-Specific E3 Ligase Causes Microcephaly and Inflammation
Zhang, J., Zhu, H., Liu, S. M., Quintero, M. K., Zhu, T., Xu, R., Cai, Y., Ye, H., & Li, H. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02979-0 · Cited by 28
Stress - Regulation of SUMO conjugation and of other Ubiquitin‐Like Modifiers
Ilic, D., Magnussen, H., & Tirard, M. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.12.010 · Cited by 23
Daida, A., Hamano, S., Ikemoto, S., Matsuura, R., Nakashima, M., Matsumoto, N., & Kato, M. (2018) · Epileptic Disorders · doi:10.1684/epd.2018.0981 · Cited by 25
Zhu, Y., Lei, Q., Li, D., Zhang, Y., Jiang, X., Hu, Z., & Xu, G. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00843 · Cited by 24
The UFM1 cascade times mitosis entry associated with microcephaly
Yu, L. F., Li, G., Deng, J., Jiang, X. J., Xue, J., Zhu, Y., Huang, W., Tang, B., & Duan, R. (2019) · The FASEB Journal · doi:10.1096/fj.201901751r · Cited by 22
Wesch, N., Löhr, F., Rogova, N. Y., Dötsch, V., & Rogov, V. V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147390 · Cited by 19
Multifaceted roles of UFMylation in health and disease
Wang, R.-N., Li, L., Zhou, J. Y., & Ran, J. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01456-9 · Cited by 21
Homozygous UBA5 Variant Leads to Hypomyelination with Thalamic Involvement and Axonal Neuropathy
Al‐Saady, M. L., Kaiser, C. S., Wakasuqui, F., Korenke, G. C., Waisfisz, Q., Polstra, A. M., Pouwels, P. J. W., Bugiani, M., van der Knaap, M. S., Lunsing, R. J., et al. (2021) · Neuropediatrics · doi:10.1055/s-0041-1724130 · Cited by 17
Eg5 UFMylation promotes spindle organization during mitosis
Li, G., Huang, Y., Han, W., Wei, L., Huang, H., Zhu, Y., Xiao, Q., Wang, Z., Huang, W., & Duan, R. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06934-w · Cited by 18
PEHO syndrome: the endpoint of different genetic epilepsies
Chitre, M., Nahorski, M. S., Stouffer, K. M., Dunning-Davies, B., Houston, H., Wakeling, E. L., Brady, A. F., Zuberi, S. M., Suri, M., Parker, A. P. J., et al. (2018) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2018-105288 · Cited by 18
UFMylation regulates translational homeostasis and cell cycle progressionPreprint
Gak, I. A., Vasiljević, D., Zerjatke, T., Yu, L., Brosch, M., Roumeliotis, T. I., Horenburg, C., Klemm, N., Bakos, G., Herrmann, A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.03.931196 · Cited by 15
The UFMylation pathway is impaired in Alzheimer’s disease
Yan, T., Heckman, M. G., Craver, E. C., Liu, C., Rawlinson, B. D., Wang, X., Murray, M. E., Dickson, D. W., Ertekin‐Taner, N., Lou, Z., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00784-y · Cited by 21
The UFM1 conjugation system in mammalian development
Yang, S., Moy, N., & Yang, R. (2023) · Developmental Dynamics · doi:10.1002/dvdy.586 · Cited by 16
The emerging roles of UFMylation in the modulation of immune responses
Liang, Z., Ning, R., Wang, Z., Kong, X., Yan, Y., Cai, Y., He, Z., Liu, X., Zou, Y., & Zhou, J. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.70019 · Cited by 16
Clearing Traffic Jams During Protein Translocation Across Membranes
Wang, L., & Ye, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.610689 · Cited by 13
Chen, H., LaFlamme, C. W., Wang, Y., Blan, A. W., Koehler, N., Moraes, R. M., Olszewski, A. R., Fuerte, E. P. A., Bonkowski, E. S., Bajpai, R., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adn8417 · Cited by 17
Badawi, S., Mohamed, F. E., Varghese, D. S., & Ali, B. R. (2023) · Traffic · doi:10.1111/tra.12902 · Cited by 14
SUMOylation of Warts kinase promotes neural stem cell reactivation
Gao, Y., Tan, Y. S., Lin, J., Chew, L. Y., Aung, H. Y., Palliyana, B., Gujar, M. R., Lin, K., Kondo, S., & Wang, H. (2024) · Nature Communications · doi:10.1038/s41467-024-52569-y · Cited by 11
The mechanistic basis and cellular functions of UFMylation
Komatsu, M., Noda, N. N., & Inada, T. (2026) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00944-y · Cited by 10
Self-citationSerrano, R. J., Oorschot, V. M. J., Palipana, D., Calcinotto, V., Sonntag, C., Ramm, G., & Bryson‐Richardson, R. J. (2023) · Brain Communications · doi:10.1093/braincomms/fcad317 · Cited by 10
Ivanov, I. S., Pacheva, I. H., Yordanova, R. V., Sotkova, I. G., Galabova, F. K., Gaberova, K., Panova, M. V., Gheneva, I., Tsvetanova, T., Noneva, K., et al. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220221100704 · Cited by 10
Retrotransposon insertions associated with risk of neurologic and psychiatric diseases
Ahn, H. W., Worman, Z., Lechsinska, A., Payer, L. M., Wang, T., Malik, N., Li, W., Burns, K. H., Nath, A., & Levin, H. L. (2022) · EMBO Reports · doi:10.15252/embr.202255197 · Cited by 10
Deep brain stimulation for medically refractory status dystonicus in UBA5 ‐related disorder
Zaman, Z., Straka, N., Pinto, A., Srouji, R., Tam, A., Periasamy, U., Stone, S. S. D., Kleinman, M. E., Northam, W. T., & Ebrahimi‐Fakhari, D. (2023) · Movement Disorders · doi:10.1002/mds.29428 · Cited by 9
Yang, S., Wang, L., Gao, R., Li, Y., Zhang, D., Wang, C., Liu, G., Na, J., Xu, P., Wang, X., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115686 · Cited by 10
Tandra, V., Anderson, T., Ayala, J. D., Weintraub, N. L., Singh, N., Li, H., & Li, J. (2023) · Cells · doi:10.3390/cells12151923 · Cited by 8
Li, Y., Gao, S., & Meng, Y. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1136154 · Cited by 8
UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery
Li, H., Meng, F., Liang, J., Wang, Y., Shan, C., & Chen, Y. (2025) · MedComm · doi:10.1002/mco2.70424 · Cited by 9
Pan, X., Alvarez, A. N., Ma, M., Lu, S., Crawford, M. W., Briere, L. C., Kanca, O., Yamamoto, S., Sweetser, D. A., Wilson, J. L., et al. (2023) · eLife · doi:10.7554/elife.89891 · Cited by 7
Chen, F., Xiang, M., Wang, Z., Yang, F., Zhou, J., Deng, Z., Wang, S., Li, P., Tew, J., Zhang, W., et al. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02414-y · Cited by 6
UFMylation of BiP / GRP78 Is Crucial for Maintenance of Endoplasmic Reticulum Homeostasis
Zhu, L., Liang, Q., Guo, Y., Wang, Y., Wang, M., & Cong, Y. (2025) · The FASEB Journal · doi:10.1096/fj.202500976rr · Cited by 8
MCM5 UFMylation regulates replication origin firing and fork progression
Li, Z., Wu, X., Liu, L., Rao, S., Liao, Y., Liu, M., Peng, B., Zhang, Q., Xia, Y., Zhai, Y., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00562-6 · Cited by 7
Pan, X., Alvarez, A. N., Ma, M., Lu, S., Crawford, M. W., Briere, L. C., Kanca, O., Yamamoto, S., Sweetser, D. A., Wilson, J. L., et al. (2023) · eLife · doi:10.7554/elife.89891.3 · Cited by 6
UFM1 at the endoplasmic reticulum: linking ER stress, ribosome quality control, and ER-phagy
Komatsu, M., & Mao, G. (2025) · Essays in Biochemistry · doi:10.1042/ebc20253054 · Cited by 5
Self-citationHomozygous TAF1C variants are associated with a novel childhood‐onset neurological phenotype
Knuutinen, O. A., Pyle, A., Suo-Palosaari, M. H., Duff, J., Froukh, T. J., Lehesjoki, A., Kangas, S. M., Cassidy, J., Maraqa, L., Keski‐Filppula, R., et al. (2020) · Clinical Genetics · doi:10.1111/cge.13827 · Cited by 5
Self-citationThe UFMylation pathway is impaired in Alzheimer’s diseasePreprint
Yan, T., Heckman, M. G., Craver, E. C., Liu, C., Rawlinson, B. D., Wang, X., Murray, M. E., Dickson, D. W., Ertekin‐Taner, N., Lou, Z., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.24.595755 · Cited by 5
Jiang, M., Zhang, C., Zhang, Z., Duan, Y., Qi, S., Zeng, Q., Wang, J., Zhang, J., Jiang, Y., Wang, Y., et al. (2024) · Genes · doi:10.3390/genes16010031 · Cited by 4
The many connections of UFMylation with Alzheimer’s disease: a comprehensive review
Yan, T., Clarkson, B. D. S., Lou, Z., Springer, W., & Fiesel, F. C. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00855-8 · Cited by 4
Ufmylation Suppresses Unfolded Protein Response to Prevent Peripartum Cardiomyopathy
Tandra, V., Zhang, L., Lee, C. M., Wu, Y., Yue, G., Li, H., Su, H., & Li, J. (2025) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2025.04.007 · Cited by 4
Clinical and genetic features of PEHO and PEHO-Like syndromes: A scoping review
Sabaie, H., Ahangar, N. K., Ghafouri‐Fard, S., Taheri, M. N., & Rezazadeh, M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110793 · Cited by 4
Chen, H., Wang, Y., Blan, A. W., Fuerte, E. P. A., Bonkowski, E. S., Bajpai, R., Pruett‐Miller, S. M., & Mefford, H. C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.25.577254 · Cited by 4
UFL1 promotes survival and function of virtual memory CD8 T cells
Bhatt, B., Kumar, K., Shi, H., Ganesan, D., Anazodo, F. I., Rathakrishnan, A., Zhu, H., Wanna, A., Jiang, C., Jayavelu, T., et al. (2025) · The Journal of Immunology · doi:10.1093/jimmun/vkae042 · Cited by 3
A rare case of hypomyelinating leukodystrophy-14 benefiting from ketogenic diet therapy
Ünalp, A., Köse, M., Karaoğlu, P., Güzin, Y., & Yılmaz, Ü. (2022) · The Turkish Journal of Pediatrics · doi:10.24953/turkjped.2021.1662 · Cited by 5
Shi, H., Cai, Y., & Liu, Y. (2026) · Biological Research · doi:10.1186/s40659-026-00676-z · Cited by 2
Pan, X., Alvarez, A. N., Ma, M., Lu, S., Crawford, M. W., Briere, L. C., Kanca, O., Yamamoto, S., Sweetser, D. A., Wilson, J. L., et al. (2023) · eLife · doi:10.7554/elife.89891.1 · Cited by 2
Pan, X., Alvarez, A. N., Ma, M., Lu, S., Crawford, M. W., Briere, L. C., Kanca, O., Yamamoto, S., Sweetser, D. A., Wilson, J. L., et al. (2023) · eLife · doi:10.7554/elife.89891.2 · Cited by 2
Cerebral Palsy Phenotypes in Genetic Epilepsies
Srivastava, S., Koh, H. Y., Smith, L. A., Poduri, A., Achkar, C. M. E., Bergin, A., Bolton, J., Ghosh, P., Harini, C., Libenson, M., et al. (2024) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2024.05.016 · Cited by 1
Studies on the functional role of UFMylation in cells (Review)
Qin, R., Tang, Y., Yuan, Y., Meng, F., Zheng, K., Yang, X., Zhao, J., & Yang, C.-H. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13556 · Cited by 1
UBA5 ‐epileptic encephalopathy: new patient, a novel variant, and a review of epileptic phenotypes
Cinnirella, C., Cinnirella, G., Campanella, C., Maccarelli, F., Accorsi, P., & Giordano, L. (2025) · Epileptic Disorders · doi:10.1002/epd2.70094 · Cited by 1
UFMylation: biological mechanisms, functions, and clinical implications
Wu, X., Yuan, Q., & Yin, Q. (2026) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2026.02.014 · Cited by 1
Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and function
Perdigão, C., Torres, J., Magnussen, H., Koch, J., Rudashevskaya, E. L., Moschref, F., Fiošins, M., Benseler, F., Wenger, S., Nilsson, T., et al. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-026-00389-6 · Cited by 1
The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease
Kuang, M., Xu, H., Huang, H., Ren, C., Huang, P., & Gong, A. (2026) · Biology · doi:10.3390/biology15050382 · Cited by 1
Mao, G., Ito, S., Ishimura, R., Sakamaki, J.-I., Sasaki, R., Uemura, T., Ishikawa, K., Komatsu‐Hirota, S., Akamatsu, W., Abe, M., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.06.026 · Cited by 1
Self-citationZhang, S., Lin, S.-Z., Wang, W., Gan, Y., Wang, C., Li, B., & Pang, Q. (2023) · Acta Epileptologica · doi:10.1186/s42494-023-00139-y · Cited by 1
Runnebohm, A. M., Indovina, C. J., Turk, S. M., Bailey, C. G., Orchard, C. J., Wade, L., Overton, D. L., Snow, B. J., & Rubenstein, E. M. (2023) · PubMed Central · doi:10.17912/micropub.biology.001021 · Cited by 1
Ishimura, R., Ito, S., Mao, G., Komatsu‐Hirota, S., Inada, T., Noda, N. N., & Komatsu, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.16.528878 · Cited by 1
Self-citationBiallelic UFM1 and UFC1 mutations expand the essential role of ufmylation in brain development
Nahorski, M. S., Maddirevula, S., Ishimura, R., Alsahli, S., Brady, A. F., Begemann, A., Mizushima, T., Guzmán‐Vega, F. J., Obata, M., Ichimura, Y., et al. (2018) · Brain · doi:10.1093/brain/awy135 · Cited by 121
Self-citationPan, X., Alvarez, A. N., Ma, M., Lu, S., Crawford, M. W., Briere, L. C., Kanca, O., Yamamoto, S., Sweetser, D. A., Wilson, J. L., et al. (2023) · medRxiv · doi:10.1101/2023.07.17.23292782
Metadata
- Authors
- Muona, M., Ishimura, R., Laari, A., Ichimura, Y., Linnankivi, T., Keski-Filppula, R., Herva, R., Rantala, H., Paetau, A., Pöyhönen, M., Obata, M., Uemura, T., Karhu, T., Bizen, N., Takebayashi, H., McKee, S., Parker, M. J., Akawi, N., McRae, J., Hurles, M. E., Kuismin, O., Kurki, M. I., Anttonen, A.-K., Tanaka, K., Palotie, A., Waguri, S., Lehesjoki, A.-E., & Komatsu, M.
- Affiliations
- University of Helsinki (FI)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Niigata University (JP)
- Oulu University Hospital (FI)
- Fukushima Medical University (JP)
- Belfast City Hospital (GB)
- Sheffield Children's NHS Foundation Trust (GB)
- Wellcome Sanger Institute (GB)
- Broad Institute (US)
- Corresponding author
- Lehesjoki, Anna-Elina
- Komatsu, Masaaki
- ORCID
- Muona, Mikko
- Ishimura, Ryosuke
- Laari, Anni
- Ichimura, Yoshinobu
- Linnankivi, Tarja
- Rantala, Heikki
- Pöyhönen, Minna
- Uemura, Takefumi
- Bizen, Norihisa
- Takebayashi, Hirohide
- McKee, Shane
- Parker, Michael J.
- Akawi, Nadia
- McRae, Jeremy
- Hurles, Matthew E.
- Kuismin, Outi
- Kurki, Mitja I.
- Anttonen, Anna-Kaisa
- Tanaka, Keiji
- Palotie, Aarno
- Waguri, Satoshi
- Lehesjoki, Anna-Elina
- Komatsu, Masaaki
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 99
- Issue
- 3
- Pages
- 683-694
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC5010641
- OpenAlex
- W2512264989
- Cited by
- 119
- References
- 33
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 13 · 2023: 21 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 10 · 2017: 4 · 2016: 1
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- Japan Society for the Promotion of Science (16J07037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- UBA5, UFM1, compound heterozygosity, biallelic variants, epilepsy, microcephaly, dystonia, spasticity, exon skipping, hypomorphic variants, loss-of-function alleles, UFC1, thioester formation, central nervous system development, neuronal apoptosis, Finnish patients
- MeSH terms
- Alleles, Animals, Animals, Newborn, Brain Diseases, Central Nervous System, Epilepsy, Exons, Fibroblasts, Finland, Gene Frequency, Heterozygote, Humans, Infant, Intellectual Disability, Microcephaly, Mutation, Neurons, Proteins, Spasms, Infantile, Cohort Studies, Apoptosis, Mice, Knockout, Ubiquitin, Ubiquitin-Activating Enzymes, Mice, Exome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
