更新于：2024-11-01

SLC9A7

更新于：2024-11-01

基本信息

别名

Na(+)/H(+) exchanger 7、NHE-7、NHE7

+ [7]

简介

Golgi Na(+), K(+)/(H+) antiporter. Mediates the electoneutral influx of Na(+) or K(+) in exchange for H(+). May contribute to the regulation of Golgi apparatus volume and pH.

关联

项与 SLC9A7 相关的药物

d9A-2

靶点

NHE1 x NHE2 x SLC9A4 x SLC9A7 x SLC9B1

作用机制

NHE1抑制剂 [+4]

在研机构

Das CeMM - Forschungszentrum für Molekulare Medizin GmbH

原研机构-

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SLC9A7 相关的临床结果

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100 项与 SLC9A7 相关的转化医学

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0 项与 SLC9A7 相关的专利（医药）

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项与 SLC9A7 相关的文献（医药）

2024-10-01·JAMA Neurology

Role of the X Chromosome in Alzheimer Disease Genetics

Article

作者: Herz, Joachim ; Greicius, Michael D. ; Merritt, Victoria ; Sherva, Richard ; Napolioni, Valerio ; Panizzon, Matthew S. ; Stewart, Ilaria ; Belloy, Michael E. ; Hauger, Richard L. ; Zhang, Rui ; Le Guen, Yann ; Gaziano, J. Michael ; Logue, Mark ; Williams, Kennedy

ImportanceThe X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.ObjectivesTo perform the first large-scale X chromosome–wide association study (XWAS) of AD.Design, Setting, and ParticipantsThis was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer’s Disease Genetics Consortium, the Alzheimer’s Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program. Risk of AD was evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024. Genetic data available from high-density single-nucleotide variant microarrays and whole-genome sequencing and summary statistics for multitissue expression and protein quantitative trait loci available from published studies were included, enabling follow-up genetic colocalization analyses. A total of 1 629 863 eligible participants were selected from referred and volunteer samples, 477 596 of whom were excluded for analysis exclusion criteria. The number of participants who declined to participate in original studies was not available.Main Outcome and MeasuresRisk of AD, reported as odds ratios (ORs) with 95% CIs. Associations were considered at X chromosome–wide (P &lt; 1 × 10−5) and genome-wide (P &lt; 5 × 10−8) significance. Primary analyses are nonstratified, while secondary analyses evaluate sex-stratified effects.ResultsAnalyses included 1 152 284 participants of non-Hispanic White, European ancestry (664 403 [57.7%] female and 487 881 [42.3%] male), including 138 558 individuals with AD. Six independent genetic loci passed X chromosome–wide significance, with 4 showing support for links between the genetic signal for AD and expression of nearby genes in brain and nonbrain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of SLC9A7 (OR, 1.03; 95% CI, 1.02-1.04) and colocalization analyses prioritizing both the SLC9A7 and nearby CHST7 genes. Of these 6 loci, 4 displayed evidence for escape from X chromosome inactivation with regard to AD risk.Conclusion and RelevanceThis large-scale XWAS of AD identified the novel SLC9A7 locus. SLC9A7 regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid β accumulation. Overall, this study advances our knowledge of AD genetics and may provide novel biological drug targets. The results further provide initial insights into elucidating the role of the X chromosome in sex-based differences in AD.

2024-08-01·Journal of Biological Chemistry

GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment

Article

作者: Morrow, Eric M ; Ouyang, Qing ; Ma, Li ; Schmidt, Michael ; Kasula, Ravi Kiran

Mutations in the endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome, an X-linked neurological disorder. NHE6 functions in regulation of endosome acidification and maturation in neurons. Using yeast two-hybrid screening with the NHE6 carboxyl terminus as bait, we identify Golgi-associated, gamma adaptin ear-containing, ADP-ribosylation factor (ARF) binding protein 1 (GGA1) as an interacting partner for NHE6. We corroborated the NHE6-GGA1 interaction using: coimmunoprecipitation; overexpressed constructs in mammalian cells; and coimmunoprecipitation of endogenously expressed GGA1 and NHE6 from neuroblastoma cells, as well as from the mouse brain. We demonstrate that GGA1 interacts with organellar NHEs (NHE6, NHE7, and NHE9) and that there is significantly less interaction with cell-surface localized NHEs (NHE1 and NHE5). By constructing hybrid NHE1/NHE6 exchangers, we demonstrate the cytoplasmic tail of NHE6 interacts most strongly with GGA1. We demonstrate the colocalization of NHE6 and GGA1 in cultured, primary hippocampal neurons, using super-resolution microscopy. We test the hypothesis that the interaction of NHE6 and GGA1 functions in the localization of NHE6 to the endosome compartment. Using subcellular fractionation experiments, we show that NHE6 is mislocalized in GGA1 KO cells, wherein we find less NHE6 in endosomes, but more NHE6 transport to lysosomes, and more Golgi retention of NHE6, with increased exocytosis to the surface plasma membrane. Consistent with NHE6 mislocalization, and Golgi retention, we find the intraluminal pH in Golgi to be alkalinized in GGA1-null cells. Our study demonstrates a new interaction between NHE6 and GGA1 which functions in the localization of this intracellular NHE to the endosome compartment.

2024-06-10·Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[Clinical and genetic analysis of a child with X-linked mental retardation due to variant of SLC9A7 gene].

Article

作者: Tamang, Spana ; Wang, Huaili ; Li, Wei ; Fu, Tianjiao ; Wang, Yao ; Zhuo, Zhihong

OBJECTIVETo explore the clinical and genetic characteristics of a child with mental retardation, language and motor developmental delay and epilepsy.METHODSA child who was admitted to the First Affiliated Hospital of Zhengzhou University in March 2020 for intermittent seizures for over two months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to high throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.RESULTSThe clinical manifestations of the child have included mental retardation, language and motor developmental delay, and seizures. High-throughput sequencing revealed that he has harbored a hemizygous splice site variant (NM_032591.3: c.1030-1G>C) of the SLC9A7 gene, which was inherited from his mother and unreported previously.CONCLUSIONThe hemizygous splice site variant (NM_032591.3: c.1030-1G>C) of the SLC9A7 gene probably underlay the disease in this child. Above finding has provided a basis for clinical diagnosis and genetic counseling.

项与 SLC9A7 相关的新闻（医药）

2023-12-29

·今日头条

最新！香港大学研究学者发现肝细胞癌潜在治疗靶点

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：小型细胞外囊泡（sEVs）通过多方面的途径介导细胞间通讯，促进肝细胞癌（HCC）的进展。 12月28日，香港大学研究学者在期刊《Cancer Communications》上在线发表题为“NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma”的研究论文，研究结果揭示了NHE7通过干扰巨噬细胞吞噬活动来减缓HCC的进展机制，揭示了一个针对晚期HCC的潜在治疗靶点。 https://onlinelibrary.wiley.com/doi/10.1002/cac2.12515 研究背景 01 肝细胞癌（HCC）是肝癌的主要亚型，占所有病例的90%以上。 HCC是一种致命的恶性肿瘤，治疗选择非常有限。尽管近年来在系统治疗、图像引导消融、放疗和手术干预方面取得了新的突破，但HCC仍然是一个全球性的健康挑战。小型细胞外囊泡（sEVs）是几乎所有细胞分泌的细胞膜包裹的颗粒（50-150 nm）。sEVs通过转移DNA、mRNA、微小RNA、蛋白质和脂质等功能性物质到其他细胞类型中，发挥关键作用，调节细胞特性并协调信号通路。在HCC中，源自转移性HCC细胞的sEV中的nidogen 1通过促进血管生成和肺内皮通透性来促进癌细胞的定植和肝外转移。从晚期HCC患者中分离得到的富含聚合免疫球蛋白受体的sEV促进了癌症的干细胞性、侵袭性和转移性。源自HCC细胞分泌的sEV中的丙酮酸激酶M2诱导单核细胞向巨噬细胞的转化以及肿瘤微环境重塑，增强了HCC的侵袭性。研究进展 02 由于NHE7的致癌作用，研究人员决定测试阻断NHE7作为HCC治疗的方法。研究人员利用Dox和IAA诱导的NHE7系统失活来抑制NHE7在由NHE7-mAID-KO MHCC97L细胞形成的已建立肿瘤中的表达。在皮下异种移植模型中，与母细胞相比，NHE7-mAID-KO MHCC97L细胞能够有效促进肿瘤形成，而Dox和IAA诱导的NHE7失活显著延缓了肿瘤形成，导致肿瘤重量减轻。从接受Dox和IAA处理的小鼠中收获的肿瘤中发现NHE7和Rab21的表达减少。在肝原位移植模型中，Dox和IAA诱导的NHE7失活抑制了肝肿瘤的生长和肺转移，分别在收获的肝和肺组织中显示出更弱的生物发光强度。对肺组织的组织学分析确认了肺部转移灶数量的减少，并且从接受Dox和IAA处理的小鼠的肿瘤中发现了NHE7和Rab21表达水平的降低。相比单独抑制NHE7或使用索拉非尼，联合应用Dox、IAA和索拉非尼的小鼠中，抑制肿瘤发生和转移的效果更加明显。从接受Dox和IAA处理的小鼠中收获的NHE7表达降低的肿瘤中，巨噬细胞吞噬作用明显降低，与使用安慰剂的小鼠形成的肿瘤相比。这些发现证明了NHE7在HCC中的作用，并表明其阻断可以阻碍HCC的生长和远程转移。研究结果 03 综上所述，研究结果揭示了NHE7通过干扰巨噬细胞吞噬活动来减缓HCC的进展机制，揭示了一个针对晚期HCC的潜在治疗靶点。参考资料： https://onlinelibrary.wiley.com/doi/10.1002/cac2.12515 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情