Details for: SLC41A1

Gene ID: 254428

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SLC41A1

Ensembl ID: ENSG00000133065

Description: solute carrier family 41 member 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • mucosal invariant T cell CL0000940
    CSI 4.8
    rCSI 3.88%
    PRS 96.57
  • choroid plexus epithelial cell CL0000706
    CSI 3.93
    rCSI 6.44%
    PRS 87.73
  • cardiac muscle cell CL0000746
    CSI 3.65
    rCSI 5.23%
    PRS 86.42
  • perivascular cell CL4033054
    CSI 3.24
    rCSI 4.43%
    PRS 95.59
  • retinal bipolar neuron CL0000748
    CSI 3.09
    rCSI 5.79%
    PRS 86.49
  • neural progenitor cell CL0011020
    CSI 3.07
    rCSI 13.49%
    PRS 83.95
  • ciliated epithelial cell CL0000067
    CSI 2.9
    rCSI 2.55%
    PRS 85.94
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.9
    rCSI 5.52%
    PRS 96.84
  • multi-ciliated epithelial cell CL0005012
    CSI 2.77
    rCSI 2.76%
    PRS 88.38
  • pancreatic acinar cell CL0002064
    CSI 2.63
    rCSI 3.5%
    PRS 95.33
  • vascular leptomeningeal cell CL4023051
    CSI 2.62
    rCSI 4.59%
    PRS 90.78
  • ependymal cell CL0000065
    CSI 2.61
    rCSI 5.3%
    PRS 78.23
  • stem cell CL0000034
    CSI 2.47
    rCSI 2.38%
    PRS 90.18
  • epithelial cell CL0000066
    CSI 2.45
    rCSI 3.77%
    PRS 82.48
  • retinal cone cell CL0000573
    CSI 2.32
    rCSI 3.73%
    PRS 86.66
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.31
    rCSI 3.69%
    PRS 94.94
  • Schwann cell CL0002573
    CSI 2.26
    rCSI 6.42%
    PRS 90.46
  • lung ciliated cell CL1000271
    CSI 2.22
    rCSI 2.57%
    PRS 88.83
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.21
    rCSI 2.64%
    PRS 83.05
  • vascular associated smooth muscle cell CL0000359
    CSI 1.99
    rCSI 6.46%
    PRS 91.8
  • epithelial cell of proximal tubule CL0002306
    CSI 1.94
    rCSI 4.75%
    PRS 88.17
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.9
    rCSI 3.36%
    PRS 82.39
  • basal cell CL0000646
    CSI 1.9
    rCSI 2.54%
    PRS 90.81
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.86
    rCSI 4.18%
    PRS 83.3
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.84
    rCSI 3.09%
    PRS 83.08
  • regular atrial cardiac myocyte CL0002129
    CSI 1.71
    rCSI 5.5%
    PRS 90.17
  • retina horizontal cell CL0000745
    CSI 1.63
    rCSI 2.49%
    PRS 90.52
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.77
    rCSI 4.81%
    PRS 87.91

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SLC41A1](/details-gene/254428) (Solute Carrier Family 41 Member 1) is a protein-coding gene located on chromosome 1q32.1. It encodes a transmembrane protein that functions as a crucial magnesium transporter, specifically operating as a sodium/magnesium exchanger ([Link](https://pubmed.ncbi.nlm.nih.gov/22031603/)). This protein plays a fundamental role in maintaining intracellular magnesium homeostasis, a process vital for numerous cellular functions. Expression data from the **Overall** context highlights its significance in a diverse array of cell types, with particularly high expression in [mucosal invariant T cell](/details-cell/CL0000940) (CSI: 4.80), [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 3.93), and [cardiac muscle cell](/details-cell/CL0000746) (CSI: 3.65). This broad yet specific expression pattern suggests a housekeeping function that is especially critical in cells with high metabolic activity, specialized transport functions, or unique immunological roles. ## Cellular Roles and Expression Landscape The expression profile of [SLC41A1](/details-gene/254428) reveals its importance across multiple physiological systems. The gene's role as a primary magnesium transporter is reflected in its high significance in cell types with high energy demands and stringent requirements for ionic balance. - **Immune System:** The highest significance score is observed in [mucosal invariant T cell](/details-cell/CL0000940), an unconventional T cell subset. This suggests a critical role for magnesium flux in MAIT cell function, potentially linking metabolic status to their activation and effector responses. - **Central Nervous System:** [SLC41A1](/details-gene/254428) is highly significant in several CNS-associated cells, including [choroid plexus epithelial cell](/details-cell/CL0000706), [retinal bipolar neuron](/details-cell/CL0000748), and [ependymal cell](/details-cell/CL0000065). This pattern indicates a key role in maintaining magnesium homeostasis within the brain and cerebrospinal fluid, which is essential for neuronal excitability and synaptic transmission. - **Cardiovascular and Muscular Tissues:** High significance in [cardiac muscle cell](/details-cell/CL0000746) underscores the importance of magnesium in cardiac function, where it is a critical cofactor for ATP and regulates ion channels essential for heart rhythm and contractility. Its expression in [perivascular cell](/details-cell/CL4033054) and [pulmonary capillary endothelial cell](/details-cell/CL4028001) also points to a role in vascular biology. - **Epithelial and Secretory Cells:** The gene is also prominent in specialized epithelial cells like [ciliated epithelial cell](/details-cell/CL0000067) and [pancreatic acinar cell](/details-cell/CL0002064), suggesting its involvement in ion transport processes related to fluid secretion and mucosal function. **Overall**, the expression landscape of [SLC41A1](/details-gene/254428) is not restricted to a single lineage but is instead characteristic of a fundamental transporter whose function is particularly pronounced in metabolically active and electrophysiologically sensitive cells. ## Pathways and Molecular Function Functional annotation confirms that [SLC41A1](/details-gene/254428) is a key player in metal ion transport. Its molecular function is defined as [magnesium ion transmembrane transporter activity](/details-go/GO:0015095) and, more specifically, [magnesium:sodium antiporter activity](/details-go/GO:0061768), as demonstrated in functional studies ([Link](https://doi.org/10.1152/ajpcell.00289.2011)). The gene's activity is integral to several biological processes, primarily [intracellular magnesium ion homeostasis](/details-go/GO:0010961) and the [cellular response to magnesium ion](/details-go/GO:0071286). These processes are vital, as magnesium is a cofactor for hundreds of enzymes and is essential for energy metabolism and cellular timekeeping ([Link](https://doi.org/10.1038/nature17407)). Cellularly, the protein is localized to the [plasma membrane](/details-go/GO:0005886), which is consistent with its role in transporting ions into and out of the cell. From a systems perspective, Reactome pathways place [SLC41A1](/details-gene/254428) within the broader categories of [Metal ion slc transporters](/details-reactome/R-HSA-425410) and [Transport of small molecules](/details-reactome/R-HSA-382551). This functional role aligns perfectly with its high expression in cells like [cardiac muscle cell](/details-cell/CL0000746) and various neurons, where tight regulation of ion gradients is paramount for function. ## Research Directions The diverse expression profile of [SLC41A1](/details-gene/254428) and its established links to human disease provide fertile ground for future research. Mutations in this gene have been associated with a nephronophthisis-like phenotype ([Link](https://doi.org/10.1681/asn.2012101034)) and potentially with Parkinson's disease ([Link](https://doi.org/10.1371/journal.pone.0071096)), highlighting its clinical relevance. **Proposed Testable Hypotheses:** 1. Given its top expression rank in [mucosal invariant T cell](/details-cell/CL0000940), we hypothesize that [SLC41A1](/details-gene/254428)-mediated magnesium transport is a rate-limiting step for MAIT cell activation and cytokine production, linking cellular metabolic state directly to immune effector function. 2. Based on the association of the p.A350V gain-of-function mutation with Parkinson's disease and the gene's high expression in neuronal cells, we hypothesize that excessive magnesium efflux mediated by mutant [SLC41A1](/details-gene/254428) leads to mitochondrial dysfunction and increased oxidative stress, contributing to the selective vulnerability of dopaminergic neurons. 3. Considering its high expression in [cardiac muscle cell](/details-cell/CL0000746), we hypothesize that genetic variants in [SLC41A1](/details-gene/254428) that alter transport kinetics are risk factors for cardiac arrhythmias by disrupting the intracellular magnesium concentrations required for stable electrical activity. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [SLC41A1](/details-gene/254428) in MAIT cells, one could use a CRISPR-Cas9 ribonucleoprotein (RNP) approach to knock out the gene in primary human MAIT cells isolated from peripheral blood. Control and knockout cells would then be stimulated with their cognate antigen (e.g., 5-A-RU presented by MR1-expressing cells). The functional consequences would be assessed by measuring key effector functions such as IFN-γ and TNF-α production via intracellular cytokine staining and flow cytometry, and cytotoxic potential using a killing assay with target cells. This would directly establish a causal link between [SLC41A1](/details-gene/254428) and MAIT cell effector capacity. **Therapeutic Potential:** [SLC41A1](/details-gene/254428) presents a complex but potentially valuable therapeutic target. As a transmembrane transporter, it is accessible to small molecule modulators. The observation that a gain-of-function mutation is linked to pathology suggests that **inhibition** of [SLC41A1](/details-gene/254428) could be a therapeutic strategy for certain neurodegenerative conditions. Conversely, loss-of-function mutations causing renal disease suggest that pharmacological **activation** could be beneficial in specific contexts. However, its widespread expression in critical tissues like the heart and brain raises a significant risk of off-target effects. Therefore, developing cell-type specific delivery systems or highly selective allosteric modulators would be essential for translating these findings into viable therapies.

Genular Protein ID: 2231328309

Symbol: S41A1_HUMAN

Name: Solute carrier family 41 member 1

UniProtKB Accession Codes:

Q8IVJ1 Q63HJ4 Q658Z5 Q659A4 Q6MZK2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 2 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12810078

Title: The human solute carrier SLC41A1 belongs to a novel eukaryotic subfamily with homology to prokaryotic MgtE Mg2+ transporters.

PubMed ID: 12810078

DOI: 10.1016/s0006-291x(03)01030-1

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 18367447

Title: SLC41A1 is a novel mammalian Mg2+ carrier.

PubMed ID: 18367447

DOI: 10.1074/jbc.m707276200

PubMed ID: 22031603

Title: Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger.

PubMed ID: 22031603

DOI: 10.1152/ajpcell.00289.2011

PubMed ID: 27074515

Title: Daily magnesium fluxes regulate cellular timekeeping and energy balance.

PubMed ID: 27074515

DOI: 10.1038/nature17407

PubMed ID: 23661805

Title: Mutation of the Mg2+ transporter SLC41A1 results in a nephronophthisis-like phenotype.

PubMed ID: 23661805

DOI: 10.1681/asn.2012101034

PubMed ID: 23976986

Title: Substitution p.A350V in Na+/Mg2+ exchanger SLC41A1, potentially associated with Parkinson's disease, is a gain-of-function mutation.

PubMed ID: 23976986

DOI: 10.1371/journal.pone.0071096

Sequence Information:

  • Length: 513
  • Mass: 54901
  • Checksum: 2B6676F9C3AF6136
  • Sequence:
    • MSSKPEPKDV HQLNGTGPSA SPCSSDGPGR EPLAGTSEFL GPDGAGVEVV IESRANAKGV 
REEDALLENG SQSNESDDVS TDRGPAPPSP LKETSFSIGL QVLFPFLLAG FGTVAAGMVL 
DIVQHWEVFQ KVTEVFILVP ALLGLKGNLE MTLASRLSTA ANIGHMDTPK ELWRMITGNM 
ALIQVQATVV GFLASIAAVV FGWIPDGHFS IPHAFLLCAS SVATAFIASL VLGMIMIGVI 
IGSRKIGINP DNVATPIAAS LGDLITLALL SGISWGLYLE LNHWRYIYPL VCAFFVALLP 
VWVVLARRSP ATREVLYSGW EPVIIAMAIS SVGGLILDKT VSDPNFAGMA VFTPVINGVG 
GNLVAVQASR ISTFLHMNGM PGENSEQAPR RCPSPCTTFF SPDVNSRSAR VLFLLVVPGH 
LVFLYTISCM QGGHTTLTLI FIIFYMTAAL LQVLILLYIA DWMVHWMWGR GLDPDNFSIP 
YLTALGDLLG TGLLALSFHV LWLIGDRDTD VGD