RUNX2

A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites.

Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28703881, PubMed:28738062). 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.

Cleidocranial dysplasia 1

CLCD1

A form of cleidocranial dysplasia, a rare skeletal disorder with significant clinical variability, even within families. Patients typically present with delayed closure of cranial sutures and fontanels with multiple Wormian bones, retarded ossification of the skull, shortening of the distal phalanges, dental anomalies including supernumerary teeth and eruption failure, clavicular hypoplasia or aplasia, wide pubic symphysis, vertebral anomalies, and short stature. CLCD1 inheritance is autosomal dominant.

None

The disease is caused by variants affecting the gene represented in this entry.

Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly

MDMHB

An autosomal dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth.

None

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).

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.

Specifically expressed in osteoblasts.

• Nucleus
• Cytoplasm

AML3, CBFA1, OSF2, PEBP2A, RUNX2, Runt-related transcription factor 2, Acute myeloid leukemia 3 protein, Core-binding factor subunit alpha-1, Oncogene AML-3, Osteoblast-specific transcription factor 2, Polyomavirus enhancer-binding protein 2 alpha A subunit, SL3-3 enhancer factor 1 alpha A subunit, SL3/AKV core-binding factor alpha A subunit, CBF-alpha-1, OSF-2, PEA2-alpha A, PEBP2-alpha A

• entrezGene:860
• omim:600211
• swissprot:Q13950

Proteins

Epigenetics

• Oncology

56648Da