| http://purl.uniprot.org/citations/31403230 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31403230 | http://www.w3.org/2000/01/rdf-schema#comment | "Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient-specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well-studied. In advance of human therapeutic trials for CAPN5 vitreoretinopathy, genetic inactivation can be used to infer the effect of protein inhibition in vivo. We created a photoreceptor-specific knockout (KO) mouse for Capn5 and compared the retinal phenotype to both wild-type and an existing Capn5 KO mouse model. In humans, CAPN5 loss-of-function (LOF) gene variants were ascertained in large exome databases from 60,706 unrelated subjects without severe disease phenotypes. Ocular examination of the retina of Capn5 KO mice by histology and electroretinography showed no significant abnormalities. In humans, there were 22 LOF CAPN5 variants located throughout the gene and in all major protein domains. Structural modeling of coding variants showed these LOF variants were nearby known disease-causing variants within the proteolytic core and in regions of high homology between human CAPN5 and 150 homologs, yet the LOF of CAPN5 was tolerated as opposed to gain-of-function disease-causing variants. These results indicate that localized inhibition of CAPN5 is a viable strategy for hyperactivating disease alleles."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.23894"xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Mahajan M."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Hsu C.W."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Tsang S.H."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Bassuk A.G."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Mahajan V.B."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Velez G."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Wert K.J."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/author | "Koch S.F."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/name | "Hum Mutat"xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/pages | "2377-2392"xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/title | "CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials."xsd:string |
| http://purl.uniprot.org/citations/31403230 | http://purl.uniprot.org/core/volume | "40"xsd:string |
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