Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease

WANG Zihao; XIA Huan; YAO Yani; YONG Yuxuan; LI Peishan; SHANG Shuying; YANG Xinling

doi:10.16766/j.cnki.issn.1674-4152.004402

Volume 24 Issue 3

Mar. 2026

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Article Navigation > Chinese Journal of General Practice > 2026 > 24(3): 386-389

WANG Zihao, XIA Huan, YAO Yani, YONG Yuxuan, LI Peishan, SHANG Shuying, YANG Xinling. Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease[J]. Chinese Journal of General Practice, 2026, 24(3): 386-389. doi: 10.16766/j.cnki.issn.1674-4152.004402

Citation:

WANG Zihao, XIA Huan, YAO Yani, YONG Yuxuan, LI Peishan, SHANG Shuying, YANG Xinling. Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease[J]. Chinese Journal of General Practice, 2026, 24(3): 386-389. doi: 10.16766/j.cnki.issn.1674-4152.004402

Citation:

WANG Zihao, XIA Huan, YAO Yani, YONG Yuxuan, LI Peishan, SHANG Shuying, YANG Xinling. Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease[J]. Chinese Journal of General Practice, 2026, 24(3): 386-389. doi: 10.16766/j.cnki.issn.1674-4152.004402

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Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease

doi: 10.16766/j.cnki.issn.1674-4152.004402

1.
Key Laboratory, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, China

Funds:

82371258

2023B03003

2022TSYCLJ0066

Received Date: 2025-06-13
Available Online: 2026-06-02

Abstract

Abstract

Objective To explore the potential association between TMEM175 gene expression levels, its genetic loci, and the risk of Parkinson's disease (PD). Methods This study was conducted from June 2023 to September 2024 at the Second Affiliated Hospital of Xinjiang Medical University. A total of 215 participants (105 patients with PD and 110 healthy controls) were included in the study. Serum TMEM175 expression levels were measured using enzyme-linked immunosorbent assay (ELISA). Genomic studies, including a genome-wide association study (GWAS) and colocalization analysis, were conducted. Single-cell RNA sequencing and chromatin accessibility analyses were employed to explore the expression characteristics of TMEM175 in brain cells. Results The expression level of TMEM175 in the PD patient group [(183.27±11.97) ng/mL] was significantly lower than that in the healthy control group [(187.28±10.24) ng/mL], with a statistically significant difference (t=2.647, P=0.009). Logistic regression analysis showed that increased TMEM175 levels significantly reduced the risk of PD, particularly in the higher concentration Q3 (185.32-＜192.92 ng/mL) and Q4 (> 192.92 ng/mL) groups, which showed statistical significance (P < 0.05). Genomic analysis indicated that TMEM175 has a protective effect on PD (OR=0.75, 95% CI: 0.55-1.01, P=0.048), and the key co-localized locus rs13063138 may influence PD risk by regulating TMEM175. Single-cell RNA sequencing data showed that TMEM175 is highly expressed in astrocytes and oligodendrocytes, suggesting its important role in glial cell function. Conclusion This study reveals the role of TMEM175 in PD from three perspectives: serum levels, genetic background, and cellular function. It provides evidence supporting TMEM175 as a potential therapeutic target for PD.
- Parkinson's disease,
- TMEM175,
- Genomics,
- Single-cell sequencing,
- Colocalization analysis

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References(15)

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[1]	MORRIS H R, SPILLANTINI M G, SUE C M, et al. The pathogenesis of Parkinson's disease[J]. Lancet, 2024, 403(10423): 293-304.
[2]	CHU Y, HIRST W D, FEDEROFF H J, et al. Nigrostriatal tau pathology in parkinsonism and Parkinson's disease[J]. Brain, 2024, 147(2): 444-457. doi: 10.1093/brain/awad388
[3]	KULCSAROVA K, SKORVANEK M, POSTUMA R B, et al. Defining Parkinson's disease: past and future[J]. J Parkinson's Dis, 2024, 14(s2): S257-S271. doi: 10.3233/JPD-230411
[4]	张春莉, 李红燕. 铁死亡在帕金森病中的研究进展[J]. 中华全科医学, 2025, 23(2): 292-295, 313. doi: 10.16766/j.cnki.issn.1674-4152.003888 ZHANG C L, LI H Y. Research progress on iron death in Parkinson's disease[J]. Chinese Journal of General Practice, 2025, 23(2): 292-295, 313. doi: 10.16766/j.cnki.issn.1674-4152.003888
[5]	任炜霞, 刘毅, 蔡丽, 等. 帕金森病的外周血标志物研究进展[J]. 医学研究杂志, 2022, 51(8): 167-172, 176. REN W X, LIU Y, CAI L, et al. Research progress on peripheral blood biomarkers of Parkinson's disease[J]. Journal of Medical Research, 2022, 51(8): 167-172, 176.
[6]	KROHN L, ÖZTVRK T N, VANDERPERRE B, et al. Genetic, structural, and functional evidence link TMEM175 to synucleinopathies[J]. Ann Neurol, 2020, 87(1): 139-153. doi: 10.1002/ana.25629
[7]	HU M Q, LI P, WANG C, et al. Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes[J]. Cell, 2022, 185(13): 2292-2308. e20. DOI: 10.1016/j.CELL.2022.05.021.
[8]	费增焱, 栗延伟, 谭军, 等. 腺苷预处理对脑缺血再灌注大鼠小胶质细胞极化及神经损伤的影响[J]. 新乡医学院学报, 2024, 41(6): 501-507. FEI Z Y, LI Y W, TAN J, et al. Effect of adenosine pretreatment on microglia polarization and nerve injury in rats with cerebral ischemia reperfusion[J]. Journal of Xinxiang Medical University, 2024, 41(6): 501-507.
[9]	WANG J, SUN X C, CHENG L F, et al. What We know about TMEM175 in Parkinson's disease[J]. CNS Neurosci Ther, 2025, 31(1): e70195. DOI: 10.1111/cns.70195.
[10]	OH S, LEE J, CHOI H J, et al. Discovery of selective inhibitors for the lysosomal Parkinson's disease channel TMEM175[J]. J Am Chem Soc, 2024, 146(33): 23230-23239. doi: 10.1021/jacs.4c05623
[11]	QU L L, LIN B Q, ZENG W P, et al. Lysosomal K⁺ channel TMEM175 promotes apoptosis and aggravates symptoms of Parkinson's disease[J]. EMBO Rep, 2022, 23(9): e53234. DOI: 10.15252/embr.202153234.
[12]	WIE J H, LIU Z J, SONG H K, et al. A growth-factor-activated lysosomal K⁺ channel regulates Parkinson's pathology[J]. Nature, 2021, 591(7850): 431-437.
[13]	ZHANG J Y, ZENG W Z, HAN Y, et al. Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel[J]. Mol Cell, 2023, 83(14): 2524-2539.e7. DOI: 10.1016/j.molcel.2023.06.004.
[14]	TANG T X, JIAN B S, LIU Z J. Transmembrane protein 175, a lysosomal ion channel related to Parkinson's disease[J]. Biomolecules, 2023, 13(5): 802. DOI: 10.3390/biom13050802.
[15]	PERDIGOTO C N. Parkinson's disease risk protein TMEM175 keeps lysosomes running on a proton leak[J]. Nat Struct Mol Biol, 2022, 29(7): 626. DOI: 10.1038/s41594-022-00809-4.

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Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease

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Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease

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