# TMEM222

## Overview
TMEM222 is a gene that encodes the transmembrane protein 222, a component of various cellular membranes including those of mitochondria, lysosomes, the Golgi apparatus, and the endoplasmic reticulum. This protein is predominantly expressed in the brain and is integral to several cellular functions, particularly in synaptic vesicles within neurons, suggesting a vital role in synaptic transmission and overall brain function (Polla2021Bi-allelic). The presence of TMEM222 in multiple organelle membranes and its involvement in neurodevelopment and synaptic functions highlight its importance in maintaining cellular integrity and facilitating neural communication. Variants of TMEM222 have been associated with intellectual disabilities, underscoring its significance in neurological development and proper brain function (Polla2021Bi-allelic).

## Function
TMEM222 encodes a transmembrane protein that is highly expressed in the brain and plays a significant role in various cellular functions. The protein is localized in different cellular membranes, including mitochondrial, lysosomal, Golgi, and endoplasmic reticulum membranes, suggesting its involvement in the structural and functional integrity of these organelles (Polla2021Bi-allelic). It is particularly noted for its presence in post-synaptic vesicles in neurons, indicating a role in synaptic function. This is supported by its co-localization with post-synaptic marker PSD95 and early endosomal and ER exit markers such as EEA1, RAB5, KIF16B, and SAR1A (Polla2021Bi-allelic).

Further studies have shown that TMEM222 is involved in the synaptic vesicles within neurons, as evidenced by its localization in vesicles of the secretory system and its partial co-localization with various synaptic and vesicular markers such as MAP2, PSD95, EEA1, RAB5, KIF16B, and SAR1A (Polla2021Bi-allelic). These findings suggest that TMEM222 may play a critical role in neurodevelopment and synaptic functions, contributing to the overall neural communication and brain function. Additionally, the identification of TMEM222 variants in patients with intellectual disabilities underscores its importance in proper neurological development and function (Polla2021Bi-allelic).

## Interactions
TMEM222, a transmembrane protein encoded by the TMEM222 gene, is involved in various cellular processes through its role as a component of the cell membrane. The protein participates in crucial protein-protein interactions that are essential for maintaining cellular functions. These interactions facilitate a range of biological activities including signal transduction pathways, which are vital for cellular communication and function. Additionally, TMEM222 is implicated in interactions that influence cellular mobility and the immune response, playing a role in the complex network of cellular signaling and defense mechanisms.

While specific details on the multiprotein complexes or transient interactions involving TMEM222 are not extensively documented, its general involvement in protein-protein interactions suggests its integration into larger protein complexes and its potential role in regulatory mechanisms within the cell. These interactions are typically governed by biochemical events and electrostatic forces that dictate the physical contacts between TMEM222 and other molecular entities within the cell.

Understanding the interactions of TMEM222 is crucial for elucidating its function in cellular processes and its potential implications in disease mechanisms. Further research into the specific interactions and partners of TMEM222 could provide deeper insights into its functional roles and therapeutic potential.


## References


[1. (Polla2021Bi-allelic) Daniel L. Polla, Andrew C. Edmondson, Sandrine Duvet, Michael E. March, Ana Berta Sousa, Anna Lehman, Dmitriy Niyazov, Fleur van Dijk, Serwet Demirdas, Marjon A. van Slegtenhorst, Anneke J.A. Kievit, Celine Schulz, Linlea Armstrong, Xin Bi, Daniel J. Rader, Kosuke Izumi, Elaine H. Zackai, Elisa de Franco, Paula Jorge, Sophie C. Huffels, Marina Hommersom, Sian Ellard, Dirk J. Lefeber, Avni Santani, Nicholas J. Hand, Hans van Bokhoven, Miao He, and Arjan P.M. de Brouwer. Bi-allelic variants in the er quality-control mannosidase gene edem3 cause a congenital disorder of glycosylation. The American Journal of Human Genetics, 108(7):1342–1349, July 2021. URL: http://dx.doi.org/10.1016/j.ajhg.2021.05.010, doi:10.1016/j.ajhg.2021.05.010. (10 citations) 10.1016/j.ajhg.2021.05.010](https://doi.org/10.1016/j.ajhg.2021.05.010)