{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Guven Tasbicen G"],"funding":["Acıbadem University","Scientific and Technological Research Council of Turkey"],"pagination":["8838"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12469775"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(18)"],"pubmed_abstract":["Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive cartilage disorder caused by biallelic variants in <i>CCN6</i>, which encodes the matricellular protein WISP3. Although WISP3 is thought to contribute to extracellular matrix (ECM) homeostasis, its precise molecular role in PPD remains unclear. To elucidate how disease-associated <i>CCN6</i> variants affect chondrocyte function, we overexpressed four variants-p.Cys52*, p.Tyr109*, p.Gly83Glu, and p.Cys114Trp-all located within the IGFBP domain, and evaluated their impact on parameters including redox balance, ER stress, ECM remodeling, gene expression, and protein-protein interactions. The p.Cys52* variant resulted in rapid degradation of WISP3, indicating a complete loss-of-function. The p.Tyr109* variant disrupted "],"journal":["International journal of molecular sciences"],"pubmed_title":["Molecular Consequences of <i>CCN6</i> Variants Encoding WISP3 in Progressive Pseudorheumatoid Dysplasia."],"pmcid":["PMC12469775"],"funding_grant_id":["2024-2170","222S011"],"pubmed_authors":["Guven Tasbicen G","Savsar B","Alanay Y","Tonbul Z","Bulbul A","Tufan A","Onat UI","Guzel E","Tahir Turanli E","Ayhan DH","Timucin AC","Bayram Akcapinar G","Akgun Dogan O"],"additional_accession":[]},"is_claimable":false,"name":"Molecular Consequences of <i>CCN6</i> Variants Encoding WISP3 in Progressive Pseudorheumatoid Dysplasia.","description":"Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive cartilage disorder caused by biallelic variants in <i>CCN6</i>, which encodes the matricellular protein WISP3. Although WISP3 is thought to contribute to extracellular matrix (ECM) homeostasis, its precise molecular role in PPD remains unclear. To elucidate how disease-associated <i>CCN6</i> variants affect chondrocyte function, we overexpressed four variants-p.Cys52*, p.Tyr109*, p.Gly83Glu, and p.Cys114Trp-all located within the IGFBP domain, and evaluated their impact on parameters including redox balance, ER stress, ECM remodeling, gene expression, and protein-protein interactions. The p.Cys52* variant resulted in rapid degradation of WISP3, indicating a complete loss-of-function. The p.Tyr109* variant disrupted ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-07-04T03:14:43.263Z","creation":"2026-07-04T03:12:56.531Z"},"accession":"S-EPMC12469775","cross_references":{"pubmed":["41009407"],"doi":["10.3390/ijms26188838"]}}