Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28738062, PubMed:28703881). Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Inhibits KAT6B-dependent transcriptional activation. Heterodimer of an alpha and a beta subunit. The alpha subunit binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80). Interacts with HIVEP3. Interacts with IFI204. Interaction with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors. Binds to HIPK3. Interacts (isoform 3) with DDX5. Interacts with FOXO1 (via a C-terminal region); the interaction inhibits RUNX2 transcriptional activity towards BGLAP. This interaction is prevented on insulin or IGF1 stimulation as FOXO1 is exported from the nucleus (By similarity). Interacts with CCNB1, KAT6A and KAT6B. Interacts with FOXP3. Interacts with TMEM119 (By similarity). Interacts with OLFM2 (By similarity). Specifically expressed in osteoblasts. A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites. Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 transactivation during osteoblastic differentiation (By similarity). Phosphorylation at Ser-451 by CDK1 promotes endothelial cell proliferation required for tumor angiogenesis probably by facilitating cell cycle progression. Isoform 3 is phosphorylated on Ser-340. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Analysis for copy-number variations revealed that a 105 kb duplication within RUNX2 segregated with the MDMHB phenotype in a region with maximum linkage. Real-time PCR for copy-number variation in genomic DNA in eight samples, as well as sequence analysis of fibroblast cDNA from one subject with MDMHB confirmed that affected family members were heterozygous for the presence of an intragenic duplication encompassing exons 3 to 5 of RUNX2. These three exons code for the Q/A domain and the functionally essential DNA-binding Runt domain of RUNX2. The RUNX2 duplication found in individuals with MDMHB leads to a gain of function (PubMed:23290074).