TY - JOUR
T1 - TMEM53 as an outer nuclear membrane regulator of cranial and tubular bone formation in craniotubular dysplasia
AU - Ren, Kaitao
AU - Fu, Yiyang
AU - Zhu, Jinhui
AU - Liu, Wanqi
AU - Han, Yuxin
AU - Zhang, Shuying
AU - Zhang, Xiaorui
AU - Chen, Mingyue
AU - Xia, Congcong
AU - Sun, Kexin
AU - Xiao, Dan
AU - Liu, Yuan
AU - Wang, Lin
AU - Qiang, Rong
AU - Shukunami, Chisa
AU - Girisha, Katta M.
AU - Ikegawa, Shiro
AU - Guo, Long
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to The Japan Society of Human Genetics 2025.
PY - 2025
Y1 - 2025
N2 - Transmembrane protein 53 (TMEM53) is an outer nuclear membrane protein that plays a crucial role in maintaining skeletal homeostasis. Pathogenic variants in TMEM53 have been identified as the genetic cause of craniotubular dysplasia, Ikegawa type (CTDI), a rare form of sclerosing bone dysplasia characterized by skull hyperostosis, cranial deformities, and increased bone density. To date, the causal association of bi-allelic pathogenic variants of TMEM53 in CTDI has been identified in 14 patients from eight unrelated families. Mechanistically, TMEM53 negatively regulates BMP–SMAD signaling by restricting the nuclear import of phosphorylated SMAD1/5/9, thereby modulating osteoblast differentiation and bone formation. This review summarizes the current understanding of TMEM53 function and the consequences of its deficiency. We aim to clarify genotype-phenotype correlations, outline therapeutic prospects for CTDI, and explore the distinct mechanisms underlying cranial and tubular bone formation.
AB - Transmembrane protein 53 (TMEM53) is an outer nuclear membrane protein that plays a crucial role in maintaining skeletal homeostasis. Pathogenic variants in TMEM53 have been identified as the genetic cause of craniotubular dysplasia, Ikegawa type (CTDI), a rare form of sclerosing bone dysplasia characterized by skull hyperostosis, cranial deformities, and increased bone density. To date, the causal association of bi-allelic pathogenic variants of TMEM53 in CTDI has been identified in 14 patients from eight unrelated families. Mechanistically, TMEM53 negatively regulates BMP–SMAD signaling by restricting the nuclear import of phosphorylated SMAD1/5/9, thereby modulating osteoblast differentiation and bone formation. This review summarizes the current understanding of TMEM53 function and the consequences of its deficiency. We aim to clarify genotype-phenotype correlations, outline therapeutic prospects for CTDI, and explore the distinct mechanisms underlying cranial and tubular bone formation.
UR - https://www.scopus.com/pages/publications/105025145277
U2 - 10.1038/s10038-025-01443-w
DO - 10.1038/s10038-025-01443-w
M3 - 文献综述
AN - SCOPUS:105025145277
SN - 1434-5161
JO - Journal of Human Genetics
JF - Journal of Human Genetics
ER -