BACKGROUND: Basement membrane-related genes (BMRGs) play a pivotal role in the pathogenesis of several diseases. However, their association with coronary artery disease (CAD) remains unexplored. Therefore, this investigation is designed to elucidate the involvement of BMRGs in CAD mechanisms. METHODS: This study incorporated CAD-related datasets (GSE113079 and GSE125856) and BMRGs. Initially, differentially expressed genes (DEGs) were identified between CAD and control (CTL) groups in GSE113079 and GSE125856. Subsequently, weighted gene coexpression network analysis (WGCNA) was carried out to identify key module genes associated with basement membranes. We then intersected the DEGs with the key module genes to obtain differentially expressed basement membrane-related genes (DE-BMRGs). Two machine learning algorithms were applied to recognize feature genes, and the intersection of these features yielded the key genes. Subsequently, immune analysis, regulatory network construction, nomogram development, and expression verification were executed based on key genes. RESULTS: Five key genes were identified: C1QTNF3, PTGER2, CAMK2N1, PRSS36, and B3GNT7. Among these, C1QTNF3 (AUC = 0.954), PTGER2 (AUC = 0.878), CAMK2N1 (AUC = 0.872), and B3GNT7 (AUC = 0.855) exhibited strong diagnostic potential in GSE113079, whereas PRSS36 showed more modest performance (AUC = 0.667). Moreover, 11 differences were observed in immune cell populations between the two groups (p < 0.05), including CD8 T cells, and we constructed a TF-miRNA-gene network comprising 112 regulatory relationships, such as the regulation of C1QTNF3 by SMAD4 and hsa-miR-302a-3p. Additionally, the expression of these five key genes was consistently lower in the CAD group across GSE113079, GSE125856, and clinical patients. CONCLUSION: This study identified five key genes associated with the basement membrane (C1QTNF3, PTGER2, CAMK2N1, PRSS36, and B3GNT7) that offer valuable scientific insights into the mechanisms of CAD. These genes represent candidate noninvasive molecular markers requiring further validation for early diagnosis and serve as preliminary candidates for subsequent therapeutic target exploration.