Transmembrane protein 147 (TMEM147)

Transmembrane protein 147 (TMEM147) is a highly conserved integral membrane protein with seven transmembrane domains, located predominantly in the endoplasmic reticulum and nuclear envelope. It forms part of the multi-pass translocon (MPT) complex, essential for the insertion of multi-pass membrane proteins into lipid bilayers. At the nuclear envelope, TMEM147 anchors the lamin B receptor (LBR) to the inner membrane, impacting nuclear architecture and chromatin organization. TMEM147 also participates in the Nicalin-NOMO complex, modulating embryonic Nodal signaling, and acts as a negative regulator of muscarinic acetylcholine receptor 3 (CHRM3)-mediated signaling. Loss-of-function variants in TMEM147 result in neurodevelopmental disorders marked by intellectual disability, characteristic facial features, severe language deficits, pseudo-Pelger-Huët anomaly (blood neutrophil morphology), and nuclear envelope instability. No drugs currently target TMEM147 clinically, but research into its structure and function supports ongoing interest in its therapeutic potential, especially for rare developmental syndromes.

Other names

BOS complex subunit TMEM147Protein NIFIE 14NIFIE14MGC1936NEDFLPHSeven transmembrane domain proteinTM147_HUMAN (UniProt)Q9BVK8 (UniProt)

No clinically validated drugs; emerging research focuses on small-molecule modulators that may influence translocon function or protein complex assembly (future therapeutic potential suggested but not realized)