TMEM64
Description
The TMEM64 (transmembrane protein 64) is a protein-coding gene located on chromosome 8.
TMEM64 plays a crucial role in regulating bone cell differentiation and metabolism. It positively influences osteoclast differentiation, a process essential for bone resorption, by regulating calcium signaling pathways triggered by TNFSF11 (RANKL). TMEM64 interacts with SERCA2, a calcium pump, in the endoplasmic reticulum (ER), leading to increased cytosolic calcium levels. This rise in calcium activates NFATC1 and promotes mitochondrial reactive oxygen species (ROS) production, ultimately driving osteoclast differentiation and activation. Conversely, TMEM64 negatively regulates osteoblast differentiation, the process responsible for bone formation. TMEM64 also promotes adipocyte differentiation, the process of fat cell formation. It achieves this by modulating the Wnt signaling pathway, a critical pathway involved in cell fate determination. By inhibiting the expression, activity, and nuclear localization of CTNNB1 (β-catenin), a key component of the Wnt pathway, TMEM64 promotes osteogenesis over adipogenesis in mesenchymal stem cells.
TMEM64 is also known as -.
Associated Diseases
- Kallmann syndrome
- osteosclerosis-ichthyosis-premature ovarian failure syndrome
- melorheostosis
- Mazabraud syndrome
- hyperostosis corticalis generalisata
- dacryocystitis-osteopoikilosis syndrome
- autosomal dominant osteosclerosis, Worth type
- osteomesopyknosis
