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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. 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

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

Genomics for SLC22A4 Gene

Regulatory Elements for SLC22A4 Gene

Enhancers for SLC22A4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH05G132292 1.8 FANTOM5 ENCODE dbSUPER 15.7 +0.6 636 5.2 MLX ZFP64 FEZF1 DMAP1 YY1 ZNF143 ZNF548 ZNF263 SP3 ZFP41 MIR3936HG RAD50 AFF4 SLC22A5 FNIP1 SLC22A4 IL4 ENSG00000202533 ZCCHC10 ENSG00000224431
GH05G132262 2.2 VISTA FANTOM5 Ensembl ENCODE dbSUPER 10.9 -28.1 -28095 7.4 HDGF PKNOX1 FOXA2 SIN3A RAD21 RARA RFX5 EGR1 ZNF366 SCRT2 P4HA2 MIR3936HG SLC22A4 SLC22A5 RAD50 RAPGEF6 GC05M132271 PDLIM4
GH05G132493 2.1 FANTOM5 Ensembl ENCODE dbSUPER 11.1 +204.1 204134 10.5 YBX1 YY1 SLC30A9 ZNF143 ZNF263 SP3 NFYC TBX21 MEF2D ZNF610 IRF1 AFF4 RAD50 SLC22A5 LOC105379175 SLC22A4 ENSG00000202533 IL4 MIR3936HG GC05P132531
GH05G132272 1.4 Ensembl ENCODE dbSUPER 12.5 -20.2 -20227 3.9 FOXA2 ATF1 ZFP64 ZNF143 FOS REST ZNF592 NFIL3 ZNF610 MYNN P4HA2 SLC22A4 P4HA2-AS1 LOC107987500 ENSG00000253067 SLC22A5 RAPGEF6 MIR3936HG GC05M132271 PDLIM4
GH05G132317 1.4 Ensembl ENCODE dbSUPER 12.4 +24.4 24361 1.5 TCF12 GLIS2 REST ZNF592 SMARCA4 PBX2 MYNN GLIS1 NR2C1 KDM1A MIR3936HG P4HA2 SLC22A4 PDLIM4 P4HA2-AS1 LOC107987500 SLC22A5 PIR38624
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SLC22A4 on UCSC Golden Path with GeneCards custom track

Promoters for SLC22A4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000186835 -84 2201 MLX ZFP64 FEZF1 DMAP1 YY1 ZNF143 ZNF548 ZNF263 SP3 ZFP41

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

Genomic Location for SLC22A4 Gene

Chromosome:
5
Start:
132,294,384 bp from pter
End:
132,344,206 bp from pter
Size:
49,823 bases
Orientation:
Plus strand

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 isoforms=57, Asn64, 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

Protein Domains 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.

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

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry 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

Gene Ontology (GO) - Cellular Components for SLC22A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA 16729965
GO:0005886 plasma membrane IC,TAS --
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 Pharma Transporter, inhibitor 39
Quinidine Approved Pharma Pore Blocker, Transporter, inhibitor 45
Amiloride Approved Pharma Channel blocker, Transporter, inhibitor 53
Cimetidine Approved Pharma Inhibition, Inhibitor, Transporter, inhibitor H2 receptor antagonist, H2 antagonist, I1 agonist 75
Guanidine Approved Pharma Transporter, inhibitor 0

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

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

Unigene Clusters for SLC22A4 Gene

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

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry 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)
genes like me logo Genes that share expression patterns with SLC22A4: view

Primer Products

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 34 35
  • 99.64 (n)
dog
(Canis familiaris)
Mammalia SLC22A4 34 35
  • 91.6 (n)
cow
(Bos Taurus)
Mammalia SLC22A4 34
  • 89.96 (n)
bta-mir-2457 35
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Slc22a4 34 16 35
  • 86.93 (n)
rat
(Rattus norvegicus)
Mammalia Slc22a4 34
  • 86.09 (n)
oppossum
(Monodelphis domestica)
Mammalia SLC22A4 35
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC22A4 35
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves SLC22A4 34 35
  • 78.02 (n)
lizard
(Anolis carolinensis)
Reptilia SLC22A4 35
  • 75 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii slc22a21 35
  • 59 (a)
ManyToMany
LOC100000685 34
  • 56.78 (n)
slc22a4 35
  • 49 (a)
ManyToMany
slc22a5 35
  • 48 (a)
ManyToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.13517 34
fruit fly
(Drosophila melanogaster)
Insecta Orct 36
  • 36 (a)
CG13610 36
  • 33 (a)
CG4630 36
  • 32 (a)
CG3790 36
  • 31 (a)
CG6600 36
  • 30 (a)
CG9317 36
  • 29 (a)
CG6356 36
  • 28 (a)
CG7084 36
  • 28 (a)
CG16727 36
  • 27 (a)
CG6126 36
  • 27 (a)
CG7458 36
  • 27 (a)
CG8654 35
  • 27 (a)
ManyToMany
CG17751 36
  • 26 (a)
CG17752 36
  • 26 (a)
CG7333 36
  • 26 (a)
CG7442 36
  • 26 (a)
CG14857 36
  • 25 (a)
CG5592 36
  • 25 (a)
CG6231 36
  • 24 (a)
worm
(Caenorhabditis elegans)
Secernentea F52F12.1a 36
  • 30 (a)
oct-1 36
  • 30 (a)
B0252.3 36
  • 27 (a)
ZK455.8a 36
  • 27 (a)
ZK455.8b 36
  • 27 (a)
K05F1.6 36
  • 26 (a)
Y82E9BR.16 36
  • 26 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 31 (a)
ManyToMany
-- 35
  • 31 (a)
ManyToMany
-- 35
  • 29 (a)
ManyToMany
-- 35
  • 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 Sequence Context AA Info Type
rs147032697 Uncertain significance 132,335,847(+) TGGTC(A/G)TGCTG intron-variant, reference, missense
rs1050152 Benign 132,340,627(+) GAATC(C/T)TCACC intron-variant, reference, missense
rs1000040643 -- 132,297,586(+) AAAGA(A/G)GCTCA intron-variant
rs1000104835 -- 132,304,547(+) AGGAG(A/G)TGGAG intron-variant
rs1000104919 -- 132,341,341(+) TGAAC(C/T)CGGGA 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)

Relevant External Links 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

(13) MalaCards diseases for SLC22A4 Gene - From: OMIM, ClinVar, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
rheumatoid arthritis
  • rheumatoid arthritis, progression of
crohn's disease
  • ileitis
tracheal disease
  • tracheal disorders
tracheal stenosis
  • stenosis of trachea
trachea leiomyoma
  • tracheal neoplasm
- 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.

Relevant External Links for SLC22A4

Genetic Association Database (GAD)
SLC22A4
Human Genome Epidemiology (HuGE) Navigator
SLC22A4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SLC22A4
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 M.V. … BrockmAPller J. (Clin. Pharmacol. Ther. 2009) 3 22 25 46 64
  2. Discovery of the ergothioneine transporter. (PMID: 15795384) Gruendemann D. … Schoemig E. (Proc. Natl. Acad. Sci. U.S.A. 2005) 2 3 4 22 64
  3. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. (PMID: 9426230) Tamai I. … Tsuji A. (FEBS Lett. 1997) 2 3 4 22 64
  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. (Mol. Pharm. 2010) 3 22 25 64
  5. Functional genetic variation in the basal promoter of the organic cation/carnitine transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5). (PMID: 19141711) Tahara H. … Giacomini K.M. (J. Pharmacol. Exp. Ther. 2009) 3 22 46 64

Products for SLC22A4 Gene

Sources for SLC22A4 Gene

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