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POTE is a primate-specific gene family that encodes cancer testis antigens that contain three domains, although the proteins vary greatly in size. The amino-terminal domain is novel and has three cysteine-rich domains of 37 amino acids. The second and third domains are rich in ankyrin repeats and spectrin-like helices respectively. In humans, 13 highly homologous paralogs are dispersed among eight chromosomes. Some members of the POTE gene family have an actin insertion at the carboxyl end of the protein. The expression of the POTE gene in normal adult tissues is restricted, but several POTE paralogs are frequently expressed in many cancers including breast, prostate, and lung cancers. We show here that POTE is expressed in several human embryonic stem (ES) cell lines. We found that UC06, WA01 and ES03 cell lines express mainly a POTE-2γ transcript but ES02 and ES04 cell lines predominantly express POTE-2α. The WA09 cell line expressed both POTE-2γ and POTE-2α. There is no detectable POTE gene expression in fetal tissues (ages 16–36 weeks). The POTE paralogs that are expressed in ES cells may have a specific function during lineage-specific differentiation of ES cells.