NCOA6 Gene: Nuclear Receptor Coactivator 6 - Function, Mutations & Disease

NCOA6 (nuclear receptor coactivator 6) encodes a transcriptional coactivator that interacts with nuclear receptors and other transcription factors to regulate gene expression. It is involved in multiple signaling pathways including steroid hormone, retinoic acid, and thyroid hormone signaling. The protein contains a basic helix-loop-helix (bHLH) domain and is essential for embryonic development, metabolism, and cell proliferation. NCOA6 is frequently amplified or overexpressed in various cancers, particularly breast and ovarian cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Nuclear receptor signaling pathway (Reactome: R-HSA-383280)

• Estrogen signaling pathway (KEGG: hsa04915)

• Thyroid hormone signaling pathway (KEGG: hsa04919)

• Retinoic acid signaling pathway

NCOA6 is a 2063-amino-acid nuclear protein containing a bHLH domain and multiple LXXLL motifs that mediate interaction with nuclear receptors. It functions as a coactivator for several transcription factors including estrogen receptor, androgen receptor, retinoic acid receptor, and thyroid hormone receptor. The protein is involved in chromatin remodeling and histone acetylation through recruitment of histone acetyltransferases. NCOA6 is essential for mouse embryonic development and plays roles in metabolism, cell growth, and differentiation. Its overexpression or amplification is observed in hormone-dependent cancers.