Details for: SLC11A1

Gene ID: 6556

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: SLC11A1

Ensembl ID: ENSG00000018280

Description: solute carrier family 11 member 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • elicited macrophage CL0000861
    CSI 43.06
    rCSI 39.54%
    PRS 79.93
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 41.61
    rCSI 32.06%
    PRS 72.87
  • Hofbauer cell CL3000001
    CSI 23.49
    rCSI 44.34%
    PRS 80.85
  • intermediate monocyte CL0002393
    CSI 22.4
    rCSI 33.8%
    PRS 76.06
  • alveolar macrophage CL0000583
    CSI 22.22
    rCSI 36.61%
    PRS 76.18
  • granulocyte CL0000094
    CSI 11.01
    rCSI 16.82%
    PRS 79.79
  • alternatively activated macrophage CL0000890
    CSI 10.94
    rCSI 13.75%
    PRS 81.99
  • monocyte CL0000576
    CSI 10.53
    rCSI 19.04%
    PRS 80.6
  • non-classical monocyte CL0000875
    CSI 9.44
    rCSI 15.12%
    PRS 86.85
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 8.95
    rCSI 11.73%
    PRS 83.38
  • mature NK T cell CL0000814
    CSI 8.94
    rCSI 11.44%
    PRS 86.34
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 8.18
    rCSI 49.52%
    PRS 86.06
  • mature B cell CL0000785
    CSI 8.18
    rCSI 7.11%
    PRS 81.35
  • Kupffer cell CL0000091
    CSI 8.1
    rCSI 18.53%
    PRS 71.61
  • mononuclear phagocyte CL0000113
    CSI 7.3
    rCSI 16.07%
    PRS 75.09
  • lung macrophage CL1001603
    CSI 6.46
    rCSI 14.44%
    PRS 78.96
  • central nervous system macrophage CL0000878
    CSI 6.42
    rCSI 21.29%
    PRS 76.12
  • CD14-positive monocyte CL0001054
    CSI 5.68
    rCSI 7.07%
    PRS 81.38
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.99
    rCSI 6.03%
    PRS 79.97
  • myeloid leukocyte CL0000766
    CSI 4.88
    rCSI 4.51%
    PRS 72.7
  • neutrophil CL0000775
    CSI 4.67
    rCSI 26.15%
    PRS 74.95
  • macrophage CL0000235
    CSI 4.65
    rCSI 8.46%
    PRS 82.9
  • myeloid cell CL0000763
    CSI 4.25
    rCSI 17.5%
    PRS 79.01
  • microglial cell CL0000129
    CSI 3.74
    rCSI 15.04%
    PRS 73.89
  • basal cell of epidermis CL0002187
    CSI 3.55
    rCSI 6.29%
    PRS 42.21
  • lung interstitial macrophage CL4033043
    CSI 3.47
    rCSI 7.78%
    PRS 85.67
  • mature microglial cell CL0002629
    CSI 3.37
    rCSI 14.02%
    PRS 71.12
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 3.31
    rCSI 35.96%
    PRS 85.54
  • adipocyte CL0000136
    CSI 3.22
    rCSI 4.13%
    PRS 62.13
  • fibroblast of lung CL0002553
    CSI 3.2
    rCSI 2.97%
    PRS 71.67
  • promonocyte CL0000559
    CSI 3.15
    rCSI 5.4%
    PRS 78.71
  • erythrocyte CL0000232
    CSI 2.99
    rCSI 6.77%
    PRS 73.11
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.38
    rCSI 6.2%
    PRS 71.4
  • tissue-resident macrophage CL0000864
    CSI 2.24
    rCSI 10.48%
    PRS 84.61
  • professional antigen presenting cell CL0000145
    CSI 1.93
    rCSI 6.63%
    PRS 87.82
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.87
    rCSI 2.26%
    PRS 54.31
  • lung ciliated cell CL1000271
    CSI 1.79
    rCSI 2.07%
    PRS 61.94
  • dendritic cell, human CL0001056
    CSI 1.34
    rCSI 2.05%
    PRS 80.21
  • colon macrophage CL0009038
    CSI 1.22
    rCSI 5.62%
    PRS 86.48
  • helper T cell CL0000912
    CSI 0.52
    rCSI 0.73%
    PRS 73.22

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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Legend:
  • Query Gene
  • 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 [SLC11A1](/details-gene/6556), or Solute Carrier Family 11 Member 1, is a protein-coding gene located on chromosome 2q35. It encodes a divalent metal cation transporter that plays a critical role in innate immunity and iron homeostasis. Functioning as a proton-coupled antiporter, [SLC11A1](/details-gene/6556) is primarily located in the membranes of late endosomes and lysosomes within phagocytic cells. Its expression is highly significant in various populations of [macrophage](/details-cell/CL0000235)s and [monocyte](/details-cell/CL0000576)s, where it is instrumental in the defense against intracellular pathogens by regulating the metal ion concentration within phagosomes. Genetic variations in [SLC11A1](/details-gene/6556) are associated with susceptibility to several infectious diseases, including tuberculosis and leprosy ([OMIM: [600266](https://omim.org/entry/600266)]). ## Cellular Roles and Expression Landscape The expression profile of [SLC11A1](/details-gene/6556) firmly establishes it as a key component of the mononuclear phagocyte system. **Overall**, the gene shows the highest significance in myeloid lineage cells, particularly those with high phagocytic capacity. It is an exceptional marker for [elicited macrophage](/details-cell/CL0000861) (CSI: 43.06) and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 41.61), indicating a pivotal role in activated and inflammatory phagocytes. The gene's prominence extends across a broad spectrum of macrophage and monocyte subtypes, including placental [Hofbauer cell](/details-cell/CL3000001)s, [alveolar macrophage](/details-cell/CL0000583)s, [Kupffer cell](/details-cell/CL0000091)s, and various circulating [monocyte](/details-cell/CL0000576) subsets like [intermediate monocyte](/details-cell/CL0002393) and [non-classical monocyte](/details-cell/CL0000875). This widespread, high-level expression underscores its fundamental function in innate immune surveillance and response across different tissues. The gene's significance is also noted in [granulocyte](/details-cell/CL0000094)s and some lymphocyte populations such as [mature NK T cell](/details-cell/CL0000814)s and [mature B cell](/details-cell/CL0000785), albeit at lower levels, suggesting a broader, yet specialized, role in the immune system. The initial identification of the gene product in peripheral blood lymphocytes supports this broader immune role ([Link](https://doi.org/10.1016/0165-2478(95)00070-l)). ## Pathways and Molecular Function Functionally, [SLC11A1](/details-gene/6556) is a versatile transmembrane transporter involved in metal ion homeostasis and host defense. Its molecular function is defined as a [metal cation:proton antiporter activity](/details-go/GO:0051139), responsible for transporting divalent cations like iron (Fe2+), manganese (Mn2+), and cadmium (Cd2+) across membranes ([Link](https://doi.org/10.1042/0264-6021:3540511)). This activity is central to its cellular location within the [lysosomal membrane](/details-go/GO:0005765) and [phagocytic vesicle membrane](/details-go/GO:0030670). The biological processes associated with [SLC11A1](/details-gene/6556) are predominantly related to the innate immune response. The gene is integral to the '[Defense response to bacterium](/details-go/GO:0042742)', '[macrophage activation](/details-go/GO:0042116)', and the regulation of '[phagocytosis](/details-go/GO:0006909)'. By pumping essential metal ions out of the phagosome, [SLC11A1](/details-gene/6556) creates a nutrient-poor environment that is hostile to engulfed microbes, a process known as nutritional immunity. This is reflected in its involvement in the '[Innate immune system](/details-pathway/R-HSA-168249)' and '[Antimicrobial peptides](/details-pathway/R-HSA-6803157)' Reactome pathways. Furthermore, its role in modulating ion concentrations impacts processes like the '[respiratory burst](/details-go/GO:0045730)' and influences broader immune signaling, including '[positive regulation of T-helper 1 type immune response](/details-go/GO:0002827)' and '[antigen processing and presentation of peptide antigen](/details-go/GO:0048002)'. ## Research Directions The established role of [SLC11A1](/details-gene/6556) in controlling intracellular pathogens, combined with its high expression in phagocytes, provides a clear basis for further investigation into its role in infectious disease and immune modulation. The association of its genetic variants with susceptibility to diseases like tuberculosis and Buruli ulcer highlights its clinical relevance ([Link](https://doi.org/10.1073/pnas.0503368102), [Link](https://doi.org/10.1038/sj.gene.6364281)). **Testable Hypotheses:** 1. Specific polymorphisms in the [SLC11A1](/details-gene/6556) promoter or coding sequence directly alter transporter efficiency in [alveolar macrophage](/details-cell/CL0000583)s, leading to impaired control of *Mycobacterium tuberculosis* replication and contributing to the variable clinical outcomes observed in infected individuals. 2. Beyond antimicrobial activity, the modulation of intracellular iron and manganese levels by [SLC11A1](/details-gene/6556) is a critical determinant of macrophage polarization. High [SLC11A1](/details-gene/6556) activity may promote a pro-inflammatory M1 phenotype by limiting metal availability for metabolic enzymes crucial for M2 differentiation, thereby shaping the immune response in contexts like tumor microenvironments or chronic inflammation. **Proposed Experiment:** To test the second hypothesis, one could utilize CRISPR-Cas9 to generate an [SLC11A1](/details-gene/6556) knockout in a human monocytic cell line (e.g., THP-1). These knockout cells and their wild-type counterparts would be differentiated into M1 ([macrophage](/details-cell/CL0000235)s polarized with LPS and IFN-γ) and M2 ([macrophage](/details-cell/CL0000235)s polarized with IL-4 and IL-13). The impact on polarization could be assessed by a multi-omics approach, including RNA-sequencing to profile the expression of canonical M1/M2 marker genes (e.g., *NOS2*, *TNF*, *ARG1*, *MRC1*), and metabolomics to measure shifts in central carbon metabolism (e.g., glycolysis vs. oxidative phosphorylation) that are characteristic of distinct macrophage activation states. **Therapeutic Potential:** As an intracellular transporter, [SLC11A1](/details-gene/6556) is not a conventional therapeutic target for inhibition. However, its function makes it a compelling candidate for therapeutic **modulation**, particularly as a host-directed therapy for infectious diseases. Small molecules that could enhance the transport activity of [SLC11A1](/details-gene/6556) might boost the antimicrobial capacity of host [macrophage](/details-cell/CL0000235)s. Such an approach could be valuable for treating infections caused by intracellular pathogens, especially those with significant antibiotic resistance, by strengthening the host's own defense mechanisms rather than directly targeting the microbe.

Genular Protein ID: 3854796060

Symbol: NRAM1_HUMAN

Name: Solute carrier family 11 member 1

UniProtKB Accession Codes:

P49279 C0H5Y3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 6 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 1 ExpressionAtlas 1 GO 53 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HAMAP 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 2 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 2 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 4 RefSeq 6 Rhea 3 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7964458

Title: Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression.

PubMed ID: 7964458

DOI: 10.1084/jem.180.5.1741

PubMed ID: 8537108

Title: Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes.

PubMed ID: 8537108

DOI: 10.1016/0165-2478(95)00070-l

PubMed ID: 10967134

Title: Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on chromosome region 2q35.

PubMed ID: 10967134

DOI: 10.1007/s003350010151

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7980580

Title: Isolation and characterization of human Nramp cDNA.

PubMed ID: 7980580

DOI: 10.1006/bbrc.1994.2572

PubMed ID: 8529098

Title: Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism.

PubMed ID: 8529098

DOI: 10.1007/bf03401567

PubMed ID: 11237855

Title: Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation antiporter.

PubMed ID: 11237855

DOI: 10.1042/0264-6021:3540511

PubMed ID: 7717395

Title: Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene.

PubMed ID: 7717395

PubMed ID: 16103355

Title: Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease.

PubMed ID: 16103355

DOI: 10.1073/pnas.0503368102

PubMed ID: 16395392

Title: Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.

PubMed ID: 16395392

DOI: 10.1038/sj.gene.6364281

Sequence Information:

  • Length: 550
  • Mass: 59872
  • Checksum: AA670763D52EEECC
  • Sequence:
    • MTGDKGPQRL SGSSYGSISS PTSPTSPGPQ QAPPRETYLS EKIPIPDTKP GTFSLRKLWA 
FTGPGFLMSI AFLDPGNIES DLQAGAVAGF KLLWVLLWAT VLGLLCQRLA ARLGVVTGKD 
LGEVCHLYYP KVPRTVLWLT IELAIVGSDM QEVIGTAIAF NLLSAGRIPL WGGVLITIVD 
TFFFLFLDNY GLRKLEAFFG LLITIMALTF GYEYVVARPE QGALLRGLFL PSCPGCGHPE 
LLQAVGIVGA IIMPHNIYLH SALVKSREID RARRADIREA NMYFLIEATI ALSVSFIINL 
FVMAVFGQAF YQKTNQAAFN ICANSSLHDY AKIFPMNNAT VAVDIYQGGV ILGCLFGPAA 
LYIWAIGLLA AGQSSTMTGT YAGQFVMEGF LRLRWSRFAR VLLTRSCAIL PTVLVAVFRD 
LRDLSGLNDL LNVLQSLLLP FAVLPILTFT SMPTLMQEFA NGLLNKVVTS SIMVLVCAIN 
LYFVVSYLPS LPHPAYFGLA ALLAAAYLGL STYLVWTCCL AHGATFLAHS SHHHFLYGLL 
EEDQKGETSG