# TMEM249

## Overview
TMEM249 is a gene that encodes the transmembrane protein 249, a component of the CatSper channel complex, which is essential for sperm motility and fertilization. As a transmembrane protein, TMEM249 plays a critical role in maintaining the structural integrity and function of the CatSper channel by interacting with specific amino acids at the dimeric interface (Zhao20223D). The gene has also been implicated in clinical contexts, particularly in ovarian cancer, where alterations in its expression are associated with chemotherapy resistance. This suggests that TMEM249 may serve as a potential biomarker for predicting treatment outcomes in cancer patients (Sharbatoghli2022Copy).

## Structure


## Function


## Clinical Significance
Alterations in the expression of the TMEM249 gene have been linked to chemotherapy resistance in ovarian cancer. Studies have shown that TMEM249, along with HSF1 and MROH1, exhibits copy number variations (CNVs) in patients resistant to neoadjuvant chemotherapy (NAC). These CNVs are not present in NAC-sensitive patients before treatment, suggesting a specific association with resistance (Sharbatoghli2022Copy). The mRNA expression levels of TMEM249 are significantly higher in ovarian serous carcinoma compared to normal tissues, and this elevated expression correlates with reduced overall survival in chemotherapy-resistant patients (Sharbatoghli2022Copy). The protein expression of TMEM249 is also enriched in chemotherapy-resistant patients, further linking its expression to poor prognosis (Sharbatoghli2022Copy).

The presence of CNVs in TMEM249 and its associated high amplification status in resistant patients indicate its potential role in NAC resistance. These findings suggest that TMEM249 could serve as a biomarker for predicting chemotherapy resistance in ovarian cancer patients, providing a target for future therapeutic strategies (Sharbatoghli2022Copy).

## Interactions
TMEM249 is a transmembrane protein that is part of the CatSper channel complex in sperm flagella. This complex is crucial for sperm motility and successful fertilization. TMEM249 is identified as a newly discovered component of the CatSper complex, interacting at the dimeric interface with specific amino acids, including Q61, R63, and T64. These interactions are important for maintaining the structural integrity and function of the CatSper channel (Zhao20223D).

The CatSper complex is composed of multiple subunits, including CATSPER1-4, CATSPERβ, γ, δ, ε, η, and TMEM249, each contributing to the channel's assembly and function. The intracellular EFCAB9-CATSPERζ subcomplex plays a role in regulating pH-dependent activation and Ca2+ sensitivity, and its absence leads to structural distortions and weakened interactions within the CatSper complex (Zhao20223D).

In Efcab9 -/- mutant sperm, the typical zigzag pattern of CatSper channels is disrupted, leading to fragmentation of the rows. This suggests that TMEM249, along with other subunits, is involved in forming the dimer interface and maintaining the structural organization of the CatSper complex (Zhao20223D).


## References


[1. (Zhao20223D) Yanhe Zhao, Huafeng Wang, Caroline Wiesehoefer, Naman B. Shah, Evan Reetz, Jae Yeon Hwang, Xiaofang Huang, Tse-en Wang, Polina V. Lishko, Karen M. Davies, Gunther Wennemuth, Daniela Nicastro, and Jean-Ju Chung. 3d structure and in situ arrangements of catsper channel in the sperm flagellum. Nature Communications, June 2022. URL: http://dx.doi.org/10.1038/s41467-022-31050-8, doi:10.1038/s41467-022-31050-8. This article has 24 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1038/s41467-022-31050-8)

[2. (Sharbatoghli2022Copy) Mina Sharbatoghli, Fahimeh Fattahi, Hamidreza Aboulkheyr Es, Arvand Akbari, Setareh Akhavan, Marzieh Ebrahimi, Mohsen Asadi-Lari, Mehdi Totonchi, and Zahra Madjd. Copy number variation of circulating tumor dna (ctdna) detected using nipt in neoadjuvant chemotherapy-treated ovarian cancer patients. Frontiers in Genetics, July 2022. URL: http://dx.doi.org/10.3389/fgene.2022.938985, doi:10.3389/fgene.2022.938985. This article has 8 citations and is from a peer-reviewed journal.](https://doi.org/10.3389/fgene.2022.938985)