ArticleGlycobiology2018
Variant in human POFUT1 reduces enzymatic activity and likely causes a recessive microcephaly, global developmental delay with cardiac and vascular features.
Article in Glycobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Structure, function, and implications of fucosyltransferases in health and disease.Nature communications · 2025Review
- POFUT1 as a cancer biomarker: insights into its oncogenic mechanisms and clinical relevance.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Review
- IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport.Cellular and molecular life sciences : CMLS · 2024Article
- Analysis of endogenous NOTCH1 from POFUT1 S162L patient fibroblasts reveals the importance of the O-fucose modification on EGF12 in human development.Glycobiology · 2024Article
- POFUT1 promotes gastric cancer progression through Notch/Wnt dual signaling pathways dependent on the parafibromin-NICD1-β-catenin complex.Journal of the Chinese Medical Association : JCMA · 2023Article
- Preliminary study on the mechanism of POFUT1 in colorectal cancer.Medical oncology (Northwood, London, England) · 2023Article
- Significant Roles of NotchMolecules (Basel, Switzerland) · 2022Review
- Generation of Properly Folded Epidermal Growth Factor-Like (EGF) Repeats and Glycosyltransferases Enables In Vitro O-Glycosylation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Regulation of myeloid and lymphoid cell development by O-glycans on Notch.Frontiers in molecular biosciences · 2022Review
- A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction.American journal of human genetics · 2021Article
- Multifaceted regulation of Notch signaling by glycosylation.Glycobiology · 2021Review
- Other Types of Glycosylation.Advances in experimental medicine and biology · 2021Article
- Congenital disorders of glycosylation: A multi-genetic disease family with multiple subcellular locations.Journal of mother and child · 2020Review
- Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.International journal of molecular sciences · 2020Article
- Article
- Epiregulin promotes trophoblast epithelial-mesenchymal transition through poFUT1 and O-fucosylation by poFUT1 on uPA.Cell proliferation · 2020Article
- POFUT1 is dispensable for structure, function and survival of mouse podocytes.American journal of translational research · 2020Article
- Multiple roles for O-glycans in Notch signalling.FEBS letters · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood. Here we report a patient with a congenital syndrome consisting of severe global developmental delay, microcephaly, heart defects, failure to thrive and liver disease with a previously unreported homozygous NM_015352.1: c.485C>T variant (p.Ser162Leu) in POFUT1 detected by exome sequencing. Both parents are heterozygotes and neither manifests any signs of DDD. No other detected variant explained the phenotype. This variant eliminated a conserved N-glycosylation sequon at Asn160 in POFUT1 and profoundly decreased POFUT1 activity in patient fibroblasts compared to control fibroblasts. Purified p.Ser162Leu mutant protein also showed much lower POFUT1 activity with a lower affinity for EGF acceptor substrate than wild type POFUT1. Eliminating the N-glycan sequon by replacing Asn160 with Gln had little effect on POFUT1 activity, suggesting that loss of the glycan is not responsible for the defect. Furthermore, the p.Ser162Leu mutant showed weaker ability to rescue Notch activity in cell-based assays. These results suggest that this N-glycan of POFUT1 is not required for its proper enzymatic function, and that the p.Ser162Leu mutation of POFUT1 likely causes global developmental delay, microcephaly with vascular and cardiac defects.
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