Transmembrane protein 263 (TMEM263)

Transmembrane protein 263 (TMEM263) is a small, highly conserved plasma membrane protein of 116 amino acids, predicted to contain two transmembrane helices[3][4][7]. It is encoded by the TMEM263 gene, which is located on human chromosome 12q23.3 and previously referenced as C12orf23 and MGC17943[2]. TMEM263 is widely and variably expressed across human tissues, with particularly high expression in the liver and bone and relevance in skeletal development[3][5]. The protein physically interacts with growth hormone 1 (GH1) and bone morphogenetic protein 2 (BMP2), key regulators of long bone growth and mineralization[1][2]. In loss-of-function studies in mice and rare human cases, absence or truncation of TMEM263 leads to impaired growth hormone signaling at the liver (by reducing GH receptor levels), resulting in dramatically decreased circulating IGF-1 and IGFBP3, postnatal growth arrest, and severe reduction in bone mass[3][4][7]. Human genetic studies (GWAS) have associated TMEM263 variants with low bone mineral density and risk of osteoporotic fracture[1][2]. TMEM263 is considered essential for proper function of the postnatal GH/IGF-1 axis, especially hepatic GH responsiveness and bone formation[3][7]. There are currently no known therapeutic drugs targeting TMEM263, nor established use as a drug target or biomarker in clinical practice. In rare human loss-of-function mutations, TMEM263 is causative for severe, lethal skeletal dysplasia[2]. Studies in animal models suggest an essential and non-redundant role in skeletal growth, while its roles in other tissues and diseases remain less defined.

Other names

TMEM263C12orf23MGC17943UPF0444 transmembrane protein C12orf23