Collectively, we identified the key signaling pathways and hub genes (CD74, COL1A1, TXNRD1, CCND1, COL5A1, SERPINH1, BCL6, ITGA10, FOS, and JUNB) in AS and AI pathological processes, which may become the potential indicative biomarkers or important regulatory targets in AS and AI pathogenesis. The gene discussed is COL5A1; the disease is aortic valve stenosis.