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Hes 6, a gene found on human chromosome 2, encodes for a transcription factor; it belongs to the basic helix-loop-helix (bHLH) family of transcription factors. The role of HES6 is that of a transcriptional repressor. HES6 binds to and suppresses HES1, and important factor in the Notch signaling pathway. Hes 6 is expressed in embyronic development involving neurogenesis, myogenesis, and thymus development.

HES 6, unlike other Hes gene products, does not bind to DNA - instead it binds to HES 1 (a transcription repressor). This interaction of HES6:HES1 promotes cell differentiation via repressing a transcription repressor; for this reason HES6 is also referred to as a transcription cofactor. Regulation of Hes 6 was found to be Notch independent and instead regulated by androgen levels. Regulation of hedgehog signaling, apoptosis, and cell migration are all proposed roles for HES 6. Hes 6 knockout mice are viable and fertile.

Overexpression of Hes 6 was found in malignant glioma and aggressive prostate cancer; this overexpression is responsible for cancer cell survival, migration, and proliferation. Silencing of Hes 6 resulted in significant reduction of proliferation and migration.