SLC12A6

Last update 08 May 2025

Basic Info

Synonyms

ACCPN, agenesis of corpus callosum and peripheral neuropathy (Andermann syndrome), Electroneutral potassium-chloride cotransporter 3

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Introduction

Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10600773, PubMed:11551954, PubMed:16048901, PubMed:18566107, PubMed:19665974, PubMed:21628467, PubMed:27485015). May contribute to cell volume homeostasis in single cells (PubMed:16048901, PubMed:27485015). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:33199848, PubMed:34031912). May contribute to cell volume homeostasis in single cells (Probable). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).

100 Clinical Results associated with SLC12A6

100 Translational Medicine associated with SLC12A6

0 Patents (Medical) associated with SLC12A6

175

Literatures (Medical) associated with SLC12A6

18 Mar 2025·Biochemistry

A “Knob Switch” Model for the Phosphoregulatory Mechanism of KCC3 at the Carboxy-Terminal Domain

Article

Author: Huang, Jing ; Xue, Jing ; Lu, Xiaoli ; Zhou, Qiang

Phosphorylation is a reversible post-translational modification that can modulate protein function. For example, phosphorylation modifications of solute carrier family 12 (SLC12) proteins function as molecular switches that precisely regulate cation-chloride ion transport. Elucidating the phosphoregulatory mechanism of SLC12 at the carboxy-terminal domain (CTD) through structural determination approaches remains challenging due to the domain's disordered and flexible nature. In this study, molecular dynamics (MD) simulations and enhanced sampling techniques were employed to investigate the CTD phosphoregulatory mechanism of SLC12A6 (also known as KCC3). Atomistic MD and metadynamics simulations revealed that the dephosphorylation of residues T940 and T997 stabilizes CTD to a favorable state that "switches on" the solvent accessibility of the inward-facing pocket. Meanwhile, phosphorylation induces distinct orientations of the CTD, transitioning the dimer into another favorable state that "switches off" the solvent accessibility. The alteration of solvent accessibility in the inward-facing pocket influences the water and ion dynamics. Based on these findings, we propose a "knob switch" model to illustrate how CTD phosphorylation regulates ion transport in KCC3.

01 Sep 2024·Experimental Gerontology

Overexpression of solute carrier family 6 member 12 promotes cell injury in Parkinson's disease via MAPK signaling pathway

Article

Author: Ma, Jianjun ; Chen, Siyuan ; Li, Xue ; Wu, Shaopu ; Yang, Hongqi ; Shi, Xiaoxue ; Peng, Haoran ; Wu, Longyu

BACKGROUNDNeurotransmitter transport disorders may play a crucial role in Parkinson's Disease (PD), and Solute carrier family 6 member 12 (SLC6A12) encodes a neurotransmitter transporter. However, the relationship between SLC6A12 and PD remains largely unexplored.METHODSWe utilized the GEO database (107 samples) and clinical data (80 samples) to investigate the role of SLC6A12 in PD through differential expression analysis, ROC analysis, and RT-qPCR experiments. Subsequently, in vitro model, axon length measurement, CCK8 assay, flow cytometry, and JC-1 assays were conducted. Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and western blot experiments were assessed to explore the functional and mechanistic pathways of SLC6A12 in PD. Finally, CIBERSORT analysis was performed to investigate the correlation between SLC6A12 and immune cells in PD.RESULTSThe expression of SLC6A12 was significantly higher in individuals with PD compared to healthy controls. Inhibiting SLC6A12 expression in PD models enhanced neuronal growth and proliferation activity while reducing cell apoptosis. Furthermore, SLC6A12 was found to be involved in neuronal development, synaptic function, and neural protein transport processes in PD, potentially regulating the MAPK signaling pathway through the Ras/Raf/MEK/ERK axis, contributing to the pathological process of PD. Additionally, SLC6A12 was implicated in immune environment disturbances in PD, notably affecting CD4 T cell expression.CONCLUSIONThis study documented the pathogenicity of SLC6A12 in PD for the first time, expanding the understanding of its molecular function and providing a potential target for precise treatment of PD.

01 Aug 2024·Journal of Molecular Biology

Protein Binder Toolbox for Studies of Solute Carrier Transporters

Article

Author: Droce, Aida ; Dürr, Katharina L ; Sauer, David B ; Gelová, Zuzana ; Burgess-Brown, Nicola A ; Kristensen, Peter ; Serrano, Iciar ; Hansen, Jesper S ; Wiedmer, Tabea ; Chi, Gamma ; Geertsma, Eric R ; Scacioc, Andreea ; Wolf, Gernot ; Štefanić, Saša ; Garcia, Julio ; Frommelt, Fabian ; Superti-Furga, Giulio ; Tremolada, Sara ; Ingles-Prieto, Alvaro ; Chang, Yung-Ning ; Scarabottolo, Lia ; Bernal, Jenifer Cuesta ; Bohstedt, Tina ; Carpenter, Elisabeth P ; Azzollini, Lucia ; Puetter, Vera

Transporters of the solute carrier superfamily (SLCs) are responsible for the transmembrane traffic of the majority of chemical substances in cells and tissues and are therefore of fundamental biological importance. As is often the case with membrane proteins that can be heavily glycosylated, a lack of reliable high-affinity binders hinders their functional analysis. Purifying and reconstituting transmembrane proteins in their lipidic environments remains challenging and standard approaches to generate binders for multi-transmembrane proteins, such as SLCs, channels or G protein-coupled receptors (GPCRs) are lacking. While generating protein binders to 27 SLCs, we produced full length protein or cell lines as input material for binder generation by selected binder generation platforms. As a result, we obtained 525 binders for 22 SLCs. We validated the binders with a cell-based validation workflow using immunofluorescent and immunoprecipitation methods to process all obtained binders. Finally, we demonstrated the potential applications of the binders that passed our validation pipeline in structural, biochemical, and biological applications using the exemplary protein SLC12A6, an ion transporter relevant in human disease. With this work, we were able to generate easily renewable and highly specific binders against SLCs, which will greatly facilitate the study of this neglected protein family. We hope that the process will serve as blueprint for the generation of binders against the entire superfamily of SLC transporters.

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SLC12A6

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