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Aliases for SLC22A4 Gene

Aliases for SLC22A4 Gene

  • Solute Carrier Family 22 Member 4 2 3 5
  • Solute Carrier Family 22 (Organic Cation/Ergothioneine Transporter), Member 4 2 3
  • Solute Carrier Family 22 (Organic Cation/Zwitterion Transporter), Member 4 2 3
  • Organic Cation/Carnitine Transporter 1 3 4
  • Deafness, Autosomal Recessive 60 2 3
  • Ergothioneine Transporter 3 4
  • ET Transporter 3 4
  • OCTN1 3 4
  • Integral Membrane Transport Protein 3
  • DFNB60 3
  • UT2H 4
  • ETT 4

External Ids for SLC22A4 Gene

Previous HGNC Symbols for SLC22A4 Gene

  • DFNB60

Previous GeneCards Identifiers for SLC22A4 Gene

  • GC05P131152
  • GC05P132077
  • GC05P131660
  • GC05P131706
  • GC05P131658
  • GC05P126822

Summaries for SLC22A4 Gene

Entrez Gene Summary for SLC22A4 Gene

  • 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]

GeneCards Summary for SLC22A4 Gene

SLC22A4 (Solute Carrier Family 22 Member 4) is a Protein Coding gene. Diseases associated with SLC22A4 include Rheumatoid Arthritis and Crohn's Disease. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Phospholipase D signaling pathway. Gene Ontology (GO) annotations related to this gene include nucleotide binding and transmembrane transporter activity. An important paralog of this gene is SLC22A5.

UniProtKB/Swiss-Prot for SLC22A4 Gene

  • Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET).

Gene Wiki entry for SLC22A4 Gene

Additional gene information for SLC22A4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC22A4 Gene

Genomics for SLC22A4 Gene

GeneHancer (GH) Regulatory Elements for SLC22A4 Gene

Promoters and enhancers for SLC22A4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05I132292 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 565.8 +0.6 636 5.2 PKNOX1 SMAD1 MLX ARNT ZFP64 ARID4B SIN3A FEZF1 DMAP1 ZNF2 SLC22A4 P4HA2 RAD50 AFF4 MIR3936HG IL4 FNIP1 ENSG00000202533 MIR3936 SLC22A5
GH05I132257 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 10.9 -34.7 -34727 5.3 HDGF SMAD1 BATF ZNF335 GLIS2 EGR1 SCRT2 ATF7 RCOR1 FOS PDLIM4 P4HA2 MIR3936HG SLC22A4 SLC22A5 KIF3A GC05M132271
GH05I132262 Enhancer 1.9 VISTA FANTOM5 Ensembl ENCODE dbSUPER 10.9 -28.1 -28095 7.4 HDGF PKNOX1 FOXA2 BATF KLF5 IRF4 RARA RFX5 EGR1 ZNF366 P4HA2 MIR3936HG SLC22A4 SLC22A5 RAD50 RAPGEF6 GC05M132271 PDLIM4
GH05I132493 Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 11.1 +204.1 204133 10.5 YBX1 YY1 SLC30A9 ZNF213 ZNF143 SP3 NFYC MEF2D ZNF610 GLIS1 IRF1 AFF4 RAD50 SLC22A5 LOC105379175 SLC22A4 IL4 ENSG00000202533 MIR3936HG GC05P132531
GH05I132484 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 7 +194.6 194619 8.2 HDGF PKNOX1 FOXA2 SMAD1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 IRF4 IRF1 RAD50 AFF4 SLC22A5 LOC102723741 LOC105379175 IL4 ENSG00000202533 SLC22A4 ENSG00000283782
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SLC22A4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SLC22A4 gene promoter:

Genomic Locations for SLC22A4 Gene

Genomic Locations for SLC22A4 Gene
chr5:132,294,384-132,344,206
(GRCh38/hg38)
Size:
49,823 bases
Orientation:
Plus strand
chr5:131,630,136-131,679,899
(GRCh37/hg19)

Genomic View for SLC22A4 Gene

Genes around SLC22A4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC22A4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC22A4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC22A4 Gene

Proteins for SLC22A4 Gene

  • Protein details for SLC22A4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H015-S22A4_HUMAN
    Recommended name:
    Solute carrier family 22 member 4
    Protein Accession:
    Q9H015
    Secondary Accessions:
    • O14546

    Protein attributes for SLC22A4 Gene

    Size:
    551 amino acids
    Molecular mass:
    62155 Da
    Quaternary structure:
    • Interacts with PDZK1.

neXtProt entry for SLC22A4 Gene

Post-translational modifications for SLC22A4 Gene

  • Glycosylation at posLast=5757, isoforms=64, and isoforms=91
  • Modification sites at PhosphoSitePlus

Other Protein References for SLC22A4 Gene

No data available for DME Specific Peptides for SLC22A4 Gene

Domains & Families for SLC22A4 Gene

Gene Families for SLC22A4 Gene

Suggested Antigen Peptide Sequences for SLC22A4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9H015

UniProtKB/Swiss-Prot:

S22A4_HUMAN :
  • Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Family:
  • Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
genes like me logo Genes that share domains with SLC22A4: view

Function for SLC22A4 Gene

Molecular function for SLC22A4 Gene

GENATLAS Biochemistry:
solute carrier family 22,member A4,polyspecific transporter of organic cations,strongly expressed in kidney
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.470 mM for TEA (at 37 degrees Celsius and pH 7.4) {ECO:0000269 PubMed:15459889, ECO:0000269 PubMed:9426230}; Vmax=0.974 nmol/min/mg enzyme toward TEA (at 37 degrees Celsius and pH 7.4) {ECO:0000269 PubMed:15459889, ECO:0000269 PubMed:9426230}; pH dependence: More active at neutral and alkaline pHs than at acidic pHs. {ECO:0000269 PubMed:15459889, ECO:0000269 PubMed:9426230};
UniProtKB/Swiss-Prot Function:
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET).
UniProtKB/Swiss-Prot Induction:
Overexpressed upon TNF treatment.

Phenotypes From GWAS Catalog for SLC22A4 Gene

Gene Ontology (GO) - Molecular Function for SLC22A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding TAS 9426230
GO:0005215 transporter activity IEA --
GO:0005515 protein binding IPI 15523054
GO:0005524 ATP binding IEA --
GO:0008513 secondary active organic cation transmembrane transporter activity TAS --
genes like me logo Genes that share ontologies with SLC22A4: view
genes like me logo Genes that share phenotypes with SLC22A4: view

Animal Models for SLC22A4 Gene

MGI Knock Outs for SLC22A4:

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC22A4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SLC22A4 Gene

Localization for SLC22A4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC22A4 Gene

Membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SLC22A4 gene
Compartment Confidence
plasma membrane 5
mitochondrion 5
extracellular 2
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SLC22A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IEA 16729965
GO:0005886 plasma membrane TAS,IC --
GO:0005887 integral component of plasma membrane TAS 9426230
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SLC22A4: view

Pathways & Interactions for SLC22A4 Gene

genes like me logo Genes that share pathways with SLC22A4: view

Gene Ontology (GO) - Biological Process for SLC22A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006641 triglyceride metabolic process IEA --
GO:0006810 transport IEA --
GO:0006811 ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0007589 body fluid secretion TAS 9426230
genes like me logo Genes that share ontologies with SLC22A4: view

No data available for SIGNOR curated interactions for SLC22A4 Gene

Drugs & Compounds for SLC22A4 Gene

(38) Drugs for SLC22A4 Gene - From: DrugBank, PharmGKB, DGIdb, FDA Approved Drugs, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Desipramine Approved, Investigational Pharma Transporter, inhibitor 39
Quinidine Approved, Investigational Pharma Pore Blocker, Transporter, inhibitor 48
Amiloride Approved Pharma Channel blocker, Transporter, inhibitor 55
Cimetidine Approved, Investigational Pharma Inhibition, Inhibitor, Transporter, inhibitor H2 receptor antagonist 81
Guanidine Approved Pharma Transporter, inhibitor 0

(6) Additional Compounds for SLC22A4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ergothioneine
  • Ergothionine
  • L-Ergothioneine
  • L-Thioneine
  • Sympectothion
  • Thiolhistidine-betaine
497-30-3
sodium
  • Sodium
  • Sodium ion
7440-23-5
O-Desmethylverapamil (D-702)
genes like me logo Genes that share compounds with SLC22A4: view

Transcripts for SLC22A4 Gene

mRNA/cDNA for SLC22A4 Gene

Unigene Clusters for SLC22A4 Gene

Solute carrier family 22 (organic cation/ergothioneine transporter), member 4:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC22A4 Gene

No ASD Table

Relevant External Links for SLC22A4 Gene

GeneLoc Exon Structure for
SLC22A4
ECgene alternative splicing isoforms for
SLC22A4

Expression for SLC22A4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SLC22A4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC22A4 Gene

This gene is overexpressed in Whole Blood (x23.9).

Protein differential expression in normal tissues from HIPED for SLC22A4 Gene

This gene is overexpressed in Nasal epithelium (65.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SLC22A4 Gene



Protein tissue co-expression partners for SLC22A4 Gene

NURSA nuclear receptor signaling pathways regulating expression of SLC22A4 Gene:

SLC22A4

SOURCE GeneReport for Unigene cluster for SLC22A4 Gene:

Hs.310591

mRNA Expression by UniProt/SwissProt for SLC22A4 Gene:

Q9H015-S22A4_HUMAN
Tissue specificity: Widely expressed. Highly expressed in whole blood, bone marrow, trachea and fetal liver. Weakly expressed in kidney, skeletal muscle, prostate, lung, pancreas, placenta, heart, uterus, spleen and spinal cord. Highly expressed in intestinal cell types affected by Crohn disease, including epithelial cells. Expressed in CD68 macrophage and CD43 T-cells but not in CD20 B-cells. Predominantly expressed in CD14 cells in peripheral blood mononuclear cells.

Evidence on tissue expression from TISSUES for SLC22A4 Gene

  • Intestine(4.4)
  • Lung(2.4)
  • Kidney(2.1)
  • Blood(2)
genes like me logo Genes that share expression patterns with SLC22A4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC22A4 Gene

Orthologs for SLC22A4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC22A4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC22A4 33 34
  • 99.64 (n)
dog
(Canis familiaris)
Mammalia SLC22A4 33 34
  • 91.6 (n)
cow
(Bos Taurus)
Mammalia SLC22A4 33
  • 89.96 (n)
bta-mir-2457 34
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Slc22a4 33 16 34
  • 86.93 (n)
rat
(Rattus norvegicus)
Mammalia Slc22a4 33
  • 86.09 (n)
oppossum
(Monodelphis domestica)
Mammalia SLC22A4 34
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC22A4 34
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves SLC22A4 33 34
  • 78.02 (n)
lizard
(Anolis carolinensis)
Reptilia SLC22A4 34
  • 75 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii slc22a21 34
  • 59 (a)
ManyToMany
LOC100000685 33
  • 56.78 (n)
slc22a4 34
  • 49 (a)
ManyToMany
slc22a5 34
  • 48 (a)
ManyToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.13517 33
fruit fly
(Drosophila melanogaster)
Insecta Orct 35
  • 36 (a)
CG13610 35
  • 33 (a)
CG4630 35
  • 32 (a)
CG3790 35
  • 31 (a)
CG6600 35
  • 30 (a)
CG9317 35
  • 29 (a)
CG6356 35
  • 28 (a)
CG7084 35
  • 28 (a)
CG16727 35
  • 27 (a)
CG6126 35
  • 27 (a)
CG7458 35
  • 27 (a)
CG8654 34
  • 27 (a)
ManyToMany
CG17751 35
  • 26 (a)
CG17752 35
  • 26 (a)
CG7333 35
  • 26 (a)
CG7442 35
  • 26 (a)
CG14857 35
  • 25 (a)
CG5592 35
  • 25 (a)
CG6231 35
  • 24 (a)
worm
(Caenorhabditis elegans)
Secernentea F52F12.1a 35
  • 30 (a)
oct-1 35
  • 30 (a)
B0252.3 35
  • 27 (a)
ZK455.8a 35
  • 27 (a)
ZK455.8b 35
  • 27 (a)
K05F1.6 35
  • 26 (a)
Y82E9BR.16 35
  • 26 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 31 (a)
ManyToMany
-- 34
  • 31 (a)
ManyToMany
-- 34
  • 29 (a)
ManyToMany
-- 34
  • 29 (a)
ManyToMany
Species where no ortholog for SLC22A4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for SLC22A4 Gene

ENSEMBL:
Gene Tree for SLC22A4 (if available)
TreeFam:
Gene Tree for SLC22A4 (if available)

Paralogs for SLC22A4 Gene

(13) SIMAP similar genes for SLC22A4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with SLC22A4: view

Variants for SLC22A4 Gene

Sequence variations from dbSNP and Humsavar for SLC22A4 Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs1050152 benign, SLC22A4 POLYMORPHISM 132,340,627(+) C/T coding_sequence_variant, missense_variant
rs147032697 uncertain-significance, not specified 132,335,847(+) A/G coding_sequence_variant, missense_variant
rs1000040643 -- 132,297,586(+) G/A intron_variant
rs1000104835 -- 132,304,547(+) G/A intron_variant
rs1000104919 -- 132,341,341(+) C/T intron_variant

Variation tolerance for SLC22A4 Gene

Residual Variation Intolerance Score: 45.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.26; 70.22% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLC22A4 Gene

Human Gene Mutation Database (HGMD)
SLC22A4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC22A4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for SLC22A4 Gene

Disorders for SLC22A4 Gene

MalaCards: The human disease database

(15) MalaCards diseases for SLC22A4 Gene - From: HGMD, ClinVar, GTR, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
rheumatoid arthritis
  • ra
crohn's disease
  • crohn disease
inflammatory bowel disease 5
  • ibd5
tracheal disease
  • tracheal disorders
interstitial emphysema
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

S22A4_HUMAN
  • Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269 PubMed:14608356}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for SLC22A4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SLC22A4: view

No data available for Genatlas for SLC22A4 Gene

Publications for SLC22A4 Gene

  1. The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. (PMID: 19536068) Tzvetkov MV … Brockmöller J (Clinical pharmacology and therapeutics 2009) 3 22 25 44 58
  2. Discovery of the ergothioneine transporter. (PMID: 15795384) Gründemann D … Schömig E (Proceedings of the National Academy of Sciences of the United States of America 2005) 2 3 4 22 58
  3. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. (PMID: 9426230) Tamai I … Tsuji A (FEBS letters 1997) 2 3 4 22 58
  4. Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. (PMID: 20020740) Nakamura T … Tamai I (Molecular pharmaceutics 2010) 3 22 25 58
  5. Functional genetic variation in the basal promoter of the organic cation/carnitine transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5). (PMID: 19141711) Tahara H … Giacomini KM (The Journal of pharmacology and experimental therapeutics 2009) 3 22 44 58

Products for SLC22A4 Gene

Sources for SLC22A4 Gene

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