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RUNX2, a nuclear protein, is a member of the RUNX family of transcription factors and has an Runt DNA-binding domain. It is essential for membranous and endochondral bone formation. It not only regulates osteoblastic differentiation and skeletal morphogenesis but also acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer and with more affinity, as a subunit of a heterodimeric complex. It plays a critical role in increasing TGFBR1 expression by osteoblasts and functions in cooperation with DLX5 or a related factor to activate osteoblast-specific gene expression. Mutations lead to disorders in bone development like cleidocranial dysplasia (CCD).
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