The ESR1 gene (estrogen receptor 1, also known as ER) encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative promoter usage and alternative splicing result in dozens of transcript variants, but the full-length nature of many of these variants has not been determined. ESR1 is altered in 2.21% of all cancers with breast invasive ductal carcinoma, invasive breast carcinoma, colon adenocarcinoma, lung adenocarcinoma, and endometrial endometrioid adenocarcinoma having the greatest prevalence of alterations.