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    SLC22A4 solute carrier family 22 member 4 [ Homo sapiens (human) ]

    Gene ID: 6583, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SLC22A4provided by HGNC
    Official Full Name
    solute carrier family 22 member 4provided by HGNC
    Primary source
    HGNC:HGNC:10968
    See related
    Ensembl:ENSG00000197208 MIM:604190; AllianceGenome:HGNC:10968
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ETTh; OCTN1; DFNB60
    Summary
    Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in bone marrow (RPKM 7.1), small intestine (RPKM 3.8) and 16 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SLC22A4 in Genome Data Viewer
    Location:
    5q31.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (132294394..132344190)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (132814292..132864084)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (131630087..131679883)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:131593943-131594732 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23063 Neighboring gene VISTA enhancer hs1449 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:131603965-131604508 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23064 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23065 Neighboring gene PDZ and LIM domain 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:131605973-131606861 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:131607809-131608310 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:131608311-131608810 Neighboring gene Sharpr-MPRA regulatory region 4855 Neighboring gene uncharacterized LOC124901063 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:131613864-131614676 Neighboring gene CAGE-defined mid-level expression enhancer upstream of SLC22A4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16315 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16316 Neighboring gene MIR3936 host gene Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:131656893-131657393 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:131657550-131658068 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:131658069-131658587 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:131681529-131681701 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr5:131690402-131691014 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23067 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16317 Neighboring gene microRNA 3936 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:131712295-131712796 Neighboring gene solute carrier family 22 member 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23068 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23069 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23070

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The ergothioneine transporter controls and indicates ergothioneine activity--a review. Gründemann D. Prev Med, 2012 May. PMID 22182480
    2. Discovery of the ergothioneine transporter. Gründemann D, et al. Proc Natl Acad Sci U S A, 2005 Apr 5. PMID 15795384, Free PMC Article
    3. Localization of Xenobiotic Transporter OCTN1/SLC22A4 in Hepatic Stellate Cells and Its Protective Role in Liver Fibrosis. Tang Y, et al. J Pharm Sci, 2016 May. PMID 27020986
    4. Investigation of the SLC22A4 gene (associated with rheumatoid arthritis in a Japanese population) in a United Kingdom population of rheumatoid arthritis patients. Barton A, et al. Arthritis Rheum, 2005 Mar. PMID 15751072
    5. Association of single nucleotide polymorphism rs3792876 in SLC22A4 gene with autoimmune thyroid disease in a Chinese Han population. Hou X, et al. BMC Med Genet, 2015 Sep 2. PMID 26329403, Free PMC Article

    See all (152) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. OCTN1 (SLC22A4) displays two different transport pathways for organic cations or zwitterions.
      Title: OCTN1 (SLC22A4) displays two different transport pathways for organic cations or zwitterions.
    2. Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke.
      Title: Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke.
    3. The ergothioneine transporter (ETT): substrates and locations, an inventory.
      Title: The ergothioneine transporter (ETT): substrates and locations, an inventory.
    4. DNA Methylation-Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia.
      Title: DNA Methylation-Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia.
    5. LPS-induced inflammation delays the transportation of ASP(+) due to down-regulation of OCTN1/2 in alveolar epithelial cells.
      Title: LPS-induced inflammation delays the transportation of ASP(+) due to down-regulation of OCTN1/2 in alveolar epithelial cells.
    6. Cetirizine Reduces Gabapentin Plasma Concentrations and Effect: Role of Renal Drug Transporters for Organic Cations.
      Title: Cetirizine Reduces Gabapentin Plasma Concentrations and Effect: Role of Renal Drug Transporters for Organic Cations.
    7. Tooth loss and adiposity: possible role of carnitine transporter (OCTN1/2) polymorphisms in women but not in men.
      Title: Tooth loss and adiposity: possible role of carnitine transporter (OCTN1/2) polymorphisms in women but not in men.
    8. Ergothioneine is a biologically important compound that has been shown to be transported by the organic cation transporter novel type 1 (OCTN1). The present study reaffirms the primacy of ergothioneine over these alternate substrates using natively expressed OCTN1 in HeLa cells.
      Title: Specificity of the ergothioneine transporter natively expressed in HeLa cells.
    9. SLC22A4 gene polymorphism rs272893 is/associated with increased risk of type 2 diabetes in Chinese Han patients.
      Title: Relationship Between SLC22A1 and SLC22A4 Gene Polymorphisms and Risk of Type 2 Diabetes in Chinese Han Population.
    10. It promotes neural stem cell differentiation into neurons.
      Title: [Possible Treatment of Neuropsychiatric Disorders by Promotion of Neuronal Differentiation through Organic Cation Transporters].
    Submit: New GeneRIF Correction See all GeneRIFs (85)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Rheumatoid arthritis
    MedGen: C0003873 OMIM: 180300 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
    EBI GWAS Catalog
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Genome-wide interaction studies reveal sex-specific asthma risk alleles.
    EBI GWAS Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Human metabolic individuality in biomedical and pharmaceutical research.
    EBI GWAS Catalog
    Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC34546, MGC40524

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables PDZ domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables acetylcholine transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables amino acid transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables amino-acid betaine transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables carnitine transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables quaternary ammonium group transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables quaternary ammonium group transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables secondary active organic cation transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables symporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in acetate ester transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in amino acid import across plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in carnitine metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in carnitine transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within carnitine transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in neurotransmitter transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in quaternary ammonium group transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in quaternary ammonium group transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sodium ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in triglyceride metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in xenobiotic transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in apical plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in basal plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    solute carrier family 22 member 4
    Names
    ET transporter
    deafness, autosomal recessive 60
    ergothioneine transporter
    integral membrane transport protein
    organic cation/carnitine transporter 1
    solute carrier family 22 (organic cation/ergothioneine transporter), member 4
    solute carrier family 22 (organic cation/zwitterion transporter), member 4

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012129.2 RefSeqGene

      Range
      4943..54739
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003059.3 → NP_003050.2  solute carrier family 22 member 4

      See identical proteins and their annotated locations for NP_003050.2

      Status: REVIEWED

      Source sequence(s)
      AC008599, BC028313, DA591407
      Consensus CDS
      CCDS4153.1
      UniProtKB/Swiss-Prot
      O14546, Q9H015
      Related
      ENSP00000200652.3, ENST00000200652.4
      Conserved Domains (2) summary
      cd06174
      Location:123 → 508
      MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...
      TIGR00898
      Location:12 → 518
      2A0119; cation transport protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      132294394..132344190
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006714675.5 → XP_006714738.1  solute carrier family 22 member 4 isoform X3

      Conserved Domains (1) summary
      cd06174
      Location:1 → 332
      MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...

    2. XM_011543589.3 → XP_011541891.1  solute carrier family 22 member 4 isoform X2

      Conserved Domains (1) summary
      TIGR00898
      Location:12 → 426
      2A0119; cation transport protein

    3. XM_047417594.1 → XP_047273550.1  solute carrier family 22 member 4 isoform X1

    4. XM_017009776.2 → XP_016865265.1  solute carrier family 22 member 4 isoform X3

      Conserved Domains (1) summary
      cd06174
      Location:1 → 332
      MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      132814292..132864084
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353249.1 → XP_054209224.1  solute carrier family 22 member 4 isoform X3

    2. XM_054353248.1 → XP_054209223.1  solute carrier family 22 member 4 isoform X2

    3. XM_054353247.1 → XP_054209222.1  solute carrier family 22 member 4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H015.3 GenPept UniProtKB/Swiss-Prot:Q9H015

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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