FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891644337> ?p ?o ?g. }

• W2891644337 endingPage "423" @default.
• W2891644337 startingPage "413" @default.
• W2891644337 abstract "Abstract Phosphomannomutase 2 Deficiency (PMM2-CDG) is the most common monogenic congenital disorder of glycosylation (CDG) affecting at least 800 patients globally. PMM2 orthologs are present in model organisms, including the budding yeast Saccharomyces cerevisiae gene SEC53. Here we describe conserved genotype-phenotype relationships across yeast and human patients between five PMM2 loss-of-function missense mutations and their orthologous SEC53 mutations. These alleles range in severity from folding defective (hypomorph) to dimerization defective (severe hypomorph) to catalytic dead (null). We included the first and second most common missense mutations – R141H, F119L respectively– and the most common compound heterozygote genotype – PMM2R141H/F119L – observed in PMM2-CDG patients. Each mutation described is expressed in haploid as well as homozygous and heterozygous diploid yeast cells at varying protein expression levels as either SEC53 protein variants or PMM2 protein variants. We developed a 384-well-plate, growth-based assay for use in a screen of the 2,560-compound Microsource Spectrum library of approved drugs, experimental drugs, tool compounds and natural products. We identified three compounds that suppress growth defects of SEC53 variants, F126L and V238M, based on the biochemical defect of the allele, protein abundance or ploidy. The rare PMM2 E139K protein variant is fully functional in yeast cells, suggesting that its pathogenicity in humans is due to the underlying DNA mutation that results in skipping of exon 5 and a nonfunctional truncated protein. Together, these results demonstrate that yeast models can be used to characterize known and novel PMM2 patient alleles in quantitative growth and enzymatic activity assays, and used as patient avatars for PMM2-CDG drug screens yielding compounds that could be rapidly cross-validated in zebrafish, rodent and human organoid models." @default.
• W2891644337 created "2018-09-27" @default.
• W2891644337 creator A5006748871 @default.
• W2891644337 creator A5014195914 @default.
• W2891644337 creator A5031075625 @default.
• W2891644337 creator A5052234825 @default.
• W2891644337 creator A5058843378 @default.
• W2891644337 creator A5088887882 @default.
• W2891644337 date "2019-02-01" @default.
• W2891644337 modified "2023-09-29" @default.
• W2891644337 title "Yeast Models of Phosphomannomutase 2 Deficiency, a Congenital Disorder of Glycosylation" @default.
• W2891644337 cites W1527068991 @default.
• W2891644337 cites W1802871763 @default.
• W2891644337 cites W1919855132 @default.
• W2891644337 cites W1975699819 @default.
• W2891644337 cites W1985567597 @default.
• W2891644337 cites W1988304552 @default.
• W2891644337 cites W1988373750 @default.
• W2891644337 cites W1992092712 @default.
• W2891644337 cites W1999425810 @default.
• W2891644337 cites W2000142729 @default.
• W2891644337 cites W2010734055 @default.
• W2891644337 cites W2015514724 @default.
• W2891644337 cites W2023418900 @default.
• W2891644337 cites W2026943916 @default.
• W2891644337 cites W2027251721 @default.
• W2891644337 cites W2031847747 @default.
• W2891644337 cites W2036779041 @default.
• W2891644337 cites W2046774615 @default.
• W2891644337 cites W2067166054 @default.
• W2891644337 cites W2084528624 @default.
• W2891644337 cites W2085229908 @default.
• W2891644337 cites W2086241911 @default.
• W2891644337 cites W2116999305 @default.
• W2891644337 cites W2120010534 @default.
• W2891644337 cites W2126715351 @default.
• W2891644337 cites W2126763484 @default.
• W2891644337 cites W2131491404 @default.
• W2891644337 cites W2146458937 @default.
• W2891644337 cites W2148537253 @default.
• W2891644337 cites W2152493965 @default.
• W2891644337 cites W2161776320 @default.
• W2891644337 cites W2278173988 @default.
• W2891644337 cites W2291595806 @default.
• W2891644337 cites W2331669280 @default.
• W2891644337 cites W2333950822 @default.
• W2891644337 cites W2338225276 @default.
• W2891644337 cites W2344691938 @default.
• W2891644337 cites W2757331398 @default.
• W2891644337 cites W2796918229 @default.
• W2891644337 cites W2883896837 @default.
• W2891644337 doi "https://doi.org/10.1534/g3.118.200934" @default.
• W2891644337 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6385982" @default.
• W2891644337 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30530630" @default.
• W2891644337 hasPublicationYear "2019" @default.
• W2891644337 type Work @default.
• W2891644337 sameAs 2891644337 @default.
• W2891644337 citedByCount "15" @default.
• W2891644337 countsByYear W28916443372019 @default.
• W2891644337 countsByYear W28916443372020 @default.
• W2891644337 countsByYear W28916443372021 @default.
• W2891644337 countsByYear W28916443372022 @default.
• W2891644337 countsByYear W28916443372023 @default.
• W2891644337 crossrefType "journal-article" @default.
• W2891644337 hasAuthorship W2891644337A5006748871 @default.
• W2891644337 hasAuthorship W2891644337A5014195914 @default.
• W2891644337 hasAuthorship W2891644337A5031075625 @default.
• W2891644337 hasAuthorship W2891644337A5052234825 @default.
• W2891644337 hasAuthorship W2891644337A5058843378 @default.
• W2891644337 hasAuthorship W2891644337A5088887882 @default.
• W2891644337 hasBestOaLocation W28916443371 @default.
• W2891644337 hasConcept C104317684 @default.
• W2891644337 hasConcept C12125453 @default.
• W2891644337 hasConcept C127716648 @default.
• W2891644337 hasConcept C135763542 @default.
• W2891644337 hasConcept C143191323 @default.
• W2891644337 hasConcept C153471976 @default.
• W2891644337 hasConcept C153911025 @default.
• W2891644337 hasConcept C180754005 @default.
• W2891644337 hasConcept C2777313579 @default.
• W2891644337 hasConcept C2777576037 @default.
• W2891644337 hasConcept C2779222958 @default.
• W2891644337 hasConcept C36823959 @default.
• W2891644337 hasConcept C501734568 @default.
• W2891644337 hasConcept C54355233 @default.
• W2891644337 hasConcept C75563809 @default.
• W2891644337 hasConcept C86803240 @default.
• W2891644337 hasConceptScore W2891644337C104317684 @default.
• W2891644337 hasConceptScore W2891644337C12125453 @default.
• W2891644337 hasConceptScore W2891644337C127716648 @default.
• W2891644337 hasConceptScore W2891644337C135763542 @default.
• W2891644337 hasConceptScore W2891644337C143191323 @default.
• W2891644337 hasConceptScore W2891644337C153471976 @default.
• W2891644337 hasConceptScore W2891644337C153911025 @default.
• W2891644337 hasConceptScore W2891644337C180754005 @default.
• W2891644337 hasConceptScore W2891644337C2777313579 @default.
• W2891644337 hasConceptScore W2891644337C2777576037 @default.
• W2891644337 hasConceptScore W2891644337C2779222958 @default.

• next