SSH2

Last update 08 May 2025

Basic Info

Synonyms

hSSH-2L, KIAA1725, Protein phosphatase Slingshot homolog 2

+ [5]

Introduction

Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein (PubMed:11832213). Required for spermatogenesis (By similarity). Involved in acrosome biogenesis, probably by regulating cofilin-mediated actin cytoskeleton remodeling during proacrosomal vesicle fusion and/or Golgi to perinuclear vesicle trafficking (By similarity).

100 Clinical Results associated with SSH2

100 Translational Medicine associated with SSH2

0 Patents (Medical) associated with SSH2

Literatures (Medical) associated with SSH2

01 Jan 2025·CNS Neuroscience & Therapeutics

Integrated Mendelian Randomization and Single‐Cell Transcriptomics Analysis Identifies Critical Blood Biomarkers and Potential Mechanisms in Epilepsy

Article

Author: Shan, Yongzhi ; Yang, Yanfeng ; Wei, Penghu ; Fu, Bin ; Shi, Jianwei ; Tang, Ting ; Xu, Jinkun ; Xie, Jing ; Liu, Quanlei ; Ye, Zuliang ; Zhao, Guoguang

ABSTRACTBackgroundEpilepsy has a genetic predisposition, yet causal factors and the dynamics of the immune environment in epilepsy are not fully understood.MethodsWe analyzed peripheral blood samples from epilepsy patients, identifying key genes associated with epilepsy risk through Mendelian randomization, using eQTLGen and genome‐wide association studies. The peripheral immune environment's composition in epilepsy was explored using CIBERSORT. An epilepsy mouse model was established to validated the expression of key genes at the transcriptomic and proteomic levels through single‐cell analysis. Relevant pathways were verified. Finally, we developed a predictive model for antiepileptic drug response in epilepsy patients.ResultsWe found that CDC25B, DNMT1, GZMA, MTX1, and SSH2 expression decreases epilepsy risk, whereas FGD3, RAF1, and SH3BP5L increase it. Epilepsy patients exhibited an altered peripheral immune profile, notably with increased activated mast cells and decreased CD4 memory activated T cells and γδ T cells. Eight genes were significantly related to this immune environment. In the animal model, FGD3, SSH2, and DNMT1 were upregulated at both mRNA and protein levels in the hippocampus. FGD3 and SSH2 are specifically elevated in microglia and are primarily associated with actin regulation. The trained predictive model was deployed on an online platform.ConclusionsThis study elucidates key genes linked to epilepsy, delineates the epilepsy immune landscape, and highlights the interaction between these domains, providing insights into potential epilepsy mechanisms and treatments.

15 Nov 2024·Medicine

Integrative analysis of single-nucleus RNA sequencing and Mendelian randomization to explore novel risk genes for Alzheimer’s disease

Article

Author: Huang, Xingya ; Zhou, Ruihao ; Dai, Fanshu ; Zhang, Biao ; Huang, Chao

In this study, we aimed to delineate cellular heterogeneity in Alzheimer’s disease (AD) and identify genetic markers contributing to its pathogenesis using integrative analysis of single-nucleus RNA sequencing (sn-RNA-Seq) and Mendelian randomization (MR). The dorsolateral prefrontal cortex sn-RNA-Seq dataset (GSE243292) was sourced from the Gene Expression Omnibus (GEO) database. Data preprocessing was conducted using the Seurat R software package, employing principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) for cell clustering and annotation. MR analysis was used to identify instrumental variables from expression quantitative trait loci (eQTL) and GWAS data by applying inverse variance weighting (IVW), weighted median (WM) and MR-Egger methods. This was complemented by leave-one-out sensitivity analysis to validate the causal relationship on AD risk genes. We identified 23 distinct cell clusters, which were annotated into eight subgroups, including oligodendrocytes, oligodendrocyte precursors, astrocytes, macrophage cells, endothelial cells, glutamatergic neurons, neural stem cells, and neurons. Notably, the number of macrophages significantly increased in the AD group. Using genome-wide association study (GWAS) summaries and eQTL data, MR analysis identified causal relationships for 7 genes with significant impacts on AD risk. Among these genes, CACNA2D3, INPP5D, RBM47, and TBXAS1 were associated with a decreased risk of AD, whereas EPB41L2, MYO1F, and SSH2 were associated with an increased risk. A leave-one-out sensitivity analysis confirmed the robustness of these findings. Expression analysis revealed that these genes were variably expressed across different cell subgroups. Except for the CACNA2D3 gene, the other 6 genes showed increased expression levels in the macrophages, particularly EPB41L2 and SSH2. Our findings highlight the potential of specific genetic markers identified through integrative analysis of sn-RNA-Seq and MR in guiding the diagnosis and therapeutic strategies for Alzheimer’s disease.

01 Jun 2023·Neuroscience bulletin

TRPM7 Kinase Domain is Part of the Rac1-SSH2-cofilin Complex Regulating F-actin in the Mouse Nervous System.

Letter

Author: Chen, Cui ; Li, Wei ; Chang, Junzhuang ; Abumaria, Nashat

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SSH2

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