As a result, we identified that RSPO3(OR 1.357, 95%CI 1.225–1.504), EPHB4(OR 1.608, 95%CI 1.285–2.013), SAA1(OR 0.901, 95%CI 0.855–0.951), SAA2(OR 0.878, 95%CI 0.822–0.939), and CD109(OR 0.915, 95%CI 0.875 − 0.958) were associated with endometriosis at the protein abundance level in the deCODE study, while FSHB(OR 3.905, 95%CI 3.018–5.054), RSPO3(OR 1.601, 95%CI 1.371–1.87), SEZ6L2(OR 1.435, 95%CI 1.223–1.684), and EPHB4(OR 1.398, 95%CI 1.196–1.634) were associated with endometriosis at the protein abundance level in the UKB-PPP study. The gene discussed is SEZ6L2; the disease is endometriosis.