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

Gene ID: 6583, updated on 5-Mar-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
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Genomic context

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Location:
5q31.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (132294394..132344190)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (132814292..132864084)
105.20220307 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 (ETT): substrates and locations, an inventory. Gründemann D, et al. FEBS Lett, 2022 May. PMID 34958679
  2. DNA Methylation-Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia. Buelow DR, et al. Clin Transl Sci, 2021 Jan. PMID 32905646, Free PMC Article
  3. [Possible Treatment of Neuropsychiatric Disorders by Promotion of Neuronal Differentiation through Organic Cation Transporters]. Nakamichi N, et al. Yakugaku Zasshi, 2019. PMID 31155524
  4. Specificity of the ergothioneine transporter natively expressed in HeLa cells. Tucker RAJ, et al. Biochem Biophys Res Commun, 2019 May 21. PMID 30929922
  5. OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues. Drenberg CD, et al. Cancer Res, 2017 Apr 15. PMID 28209616, Free PMC Article

See all (147) 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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

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

Genotypes

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 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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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_2023_10

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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