Ask about this productRelated genes to: COG4 Blocking Peptide
- Gene:
- COG4 NIH gene
- Name:
- component of oligomeric golgi complex 4
- Previous symbol:
- -
- Synonyms:
- COD1, DKFZP586E1519
- Chromosome:
- 16q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-05-09
- Date modifiied:
- 2015-08-24
Related products to: COG4 Blocking Peptide
Related articles to: COG4 Blocking Peptide
- Retinitis pigmentosa (RP) is a leading cause of inherited blindness, yet current gene supplementation strategies are limited by heterogeneous responses, with more than 40% of patients showing insufficient rescue. Moreover, oxidative stress constitutes a defining pathological feature of RP and critically impairs the efficacy of gene therapy. Consistently, transcriptomic and ultrastructural analyses of Pde6b (rd10) retinas revealed early and progressive dysregulation of oxidative stress-related pathways and photoreceptor degeneration. To overcome this barrier, we engineered an adeno-associated virus (AAV) vector covalently conjugated with a catalytic G-quadruplex-hemin DNAzyme (CoG4) via genetic code expansion and click chemistry. This design enables synchronized delivery of CoG4 and therapeutic Pde6b into photoreceptors, where CoG4 directly scavenges excess ROS and restores mitochondrial homeostasis, thereby creating a favorable microenvironment for gene supplementation. In rd10 mice, AAV-CoG4 treatment resulted in sustained expression of Pde6b, preservation of photoreceptor morphology, restoration of rod and cone function as evidenced by electroretinogram, and improved visual behavior, outperforming AAV or CoG4 monotherapies. Our findings establish oxidative stress as a major barrier to retinal gene therapy and demonstrate a dual-function platform that couples microenvironment modulation with genetic correction, offering a broadly applicable strategy for treating degenerative retinal diseases. - Source: PubMed
Publication date: 2026/05/13
Wu FuhuaWu HaipingYang JialiangWang HaolinPan ShengliuZhan YuxiLiao HuChen YuhanWu XiaweiYang Zhenglin - Alzheimer disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA sequencing (RNA-seq) and genotype data from NHW (n = 235), African American (AA; n = 224), and Hispanic (HISP; n = 292) Multi-Ancestry Genomics, Epigenomics, and Transcriptomics of Alzheimer's (MAGENTA) participants. Using sum of shared single effects (SuShiE) for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse-variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (false discovery rate [FDR] <0.05, posterior inclusion probability [PIP] >0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the genome-wide association study (GWAS) index SNP rs6733839 (r ≈ 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD. - Source: PubMed
Publication date: 2026/04/30
Sun XinyuMews MakaelaWheeler Nicholas RBenchek PenelopeGu TianjieGomez LissetteRay NicholasReitz ChristianeNaj Adam CBelow Jennifer ElizabethTosto GiuseppeCornejo-Olivas MarioByrd Goldie SFeliciano-Astacio Briseida ECelis KatrinaRajabli FaridKunkle Brian WPericak-Vance Margaret AHaines Jonathan LGriswold Anthony JBush William S - Saul-Wilson syndrome (SWS) is a skeletal dysplasia characterized by primordial dwarfism and progeroid features caused by a recurrent dominant COG4 variant (p.G516R). We previously showed that this mutation accelerates Golgi retrograde trafficking and disrupts glycosylation of the proteoglycan decorin, while zebrafish models revealed defects in chondrocyte elongation and intercalation. We have also shown that the SW1353 chondrosarcoma cells carrying the SWS variant exhibit reduced secretion of extracellular matrix (ECM) components. While these results indicate a critical function of COG4 in Golgi processing, the developmental process leading to skeletal dysplasia in SWS patients remains unknown. Here, we generated patient-derived iPSC cartilage organoids (SWS organoids), modeling early human chondrogenesis. SWS organoids failed to produce cartilage structures and displayed poor expression of chondrogenic markers. Time-course RNA-seq analysis of the chondrogenic process revealed reduced activation of gene networks involved in skeletal development, ECM organization, ossification, and glycosaminoglycan metabolism. Spatial multiomic analysis of protein and glycosylation by CODEX and GLYPH imaging revealed an altered chondrogenic trajectory, persistence of mesenchymal states, global glycosylation changes, and reduced deposition of chondroitin sulfate proteoglycans. These results indicate that the COG4 mutation disrupts ECM glycosylation and chondrogenic commitment, and that SWS organoids model early defects in cartilage formation underlies impaired skeletal growth in SWS. - Source: PubMed
Publication date: 2026/04/14
Mahajan SonalAncel SaraAscone GiulianaKaur RajdeepTorres JuancarlosMurad RabiWang Yu XinFerreira Carlos RFreeze Hudson H - Saul Wilson syndrome is an extremely rare genetic disorder caused by heterozygous de novo mutations in the gene. We report the first case from Saudi Arabia with previously unreported facial dysmorphic features, expanding the known phenotypic spectrum and emphasizing the importance of recognizing phenotypic variability in rare disorders. - Source: PubMed
Publication date: 2026/02/08
Bin Owaimer Saad AAbusrair Fatimah HMutlaq May RFaqeih Eissa AAbu-Safieh Leen - Alzheimer's disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on Non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA-seq and genotype data from reported NHW (n=235), African American (AA; n=224), and Hispanic (HISP; n=292) participants in MAGENTA. Using SuShiE for multi-population fine-mapping, we identified credible sets of eQTLs for 8,748 genes and improved fine-mapping precision relative to analyses using fewer populations. eQTL effects were largely shared across populations, with population-specific regulation for a subset of genes. Population-stratified TWAS and sample size-weighted meta-analysis (FUSION + MAFOCUS) prioritized and and fine-mapped nine genes (FDR<0.05, PIP>0.8), including established AD loci (, , ) with consistent effects across populations. Importantly, at we fine-mapped regulatory variants associated with gene expression and AD risk beyond the GWAS index SNP-most notably rs11682128, which is only in modest LD with rs6733839 ( )-demonstrating that multi-population TWAS can implicate additional functional variants not captured by single-SNP GWAS signals. We also discovered a novel association between COG4 expression and AD in NHW, implicating Golgi apparatus function. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several associations replicated directionally across ancestries, with statistical significance most evident in NHW. Our results show that multi-population fine-mapping improves eQTL resolution and TWAS interpretability, reveals regulatory variants beyond GWAS index SNPs, and underscores the need to expand non-European AD cohorts to resolve shared and population-specific mechanisms. - Source: PubMed
Publication date: 2025/11/05
Sun XinyuMews MakaelaWheeler Nicholas RBenchek PenelopeGu TianjieGomez LissetteRay NicholasReitz ChristianeNaj Adam CBelow Jennifer ElizabethTosto GiuseppeCornejo-Olivas MarioByrd Goldie SFeliciano-Astacio Briseida ECelis KatrinaRajabli FaridKunkle Brian WPericak-Vance Margaret AHaines Jonathan LGriswold Anthony JBush William S