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Aliases for SLC12A4 Gene

Aliases for SLC12A4 Gene

  • Solute Carrier Family 12 Member 4 2 3 5
  • Solute Carrier Family 12 (Potassium/Chloride Transporter), Member 4 2 3
  • Electroneutral Potassium-Chloride Cotransporter 1 3 4
  • Erythroid K-Cl Cotransporter 1 3 4
  • HKCC1 3 4
  • KCC1 3 4
  • Solute Carrier Family 12 (Potassium/Chloride Transporters), Member 4 3
  • Potassium/Chloride Cotransporter 1 3
  • CTC-479C5.17 3

External Ids for SLC12A4 Gene

Previous GeneCards Identifiers for SLC12A4 Gene

  • GC16M058673
  • GC16M068355
  • GC16M067713
  • GC16M067754
  • GC16M066535
  • GC16M067979
  • GC16M053850

Summaries for SLC12A4 Gene

Entrez Gene Summary for SLC12A4 Gene

  • This gene encodes a member of the SLC12A transporter family. The encoded protein mediates the coupled movement of potassium and chloride ions across the plasma membrane. This gene is expressed ubiquitously. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

GeneCards Summary for SLC12A4 Gene

SLC12A4 (Solute Carrier Family 12 Member 4) is a Protein Coding gene. Diseases associated with SLC12A4 include Agenesis Of The Corpus Callosum With Peripheral Neuropathy and Sickle Cell Disease. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. GO annotations related to this gene include protein kinase binding and cation:chloride symporter activity. An important paralog of this gene is SLC12A6.

UniProtKB/Swiss-Prot for SLC12A4 Gene

  • Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.

Gene Wiki entry for SLC12A4 Gene

Additional gene information for SLC12A4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC12A4 Gene

Genomics for SLC12A4 Gene

Regulatory Elements for SLC12A4 Gene

Enhancers for SLC12A4 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
GH16H067555 1.5 Ensembl ENCODE dbSUPER 19.4 +413.3 413293 1 ZNF493 ZFP64 ZNF121 FOS KLF7 ZNF202 ZC3H11A REST ZNF623 ZNF518A ZDHHC1 EDC4 CENPT ENSG00000260465 CTCF ENKD1 NAE1 E2F4 ENSG00000263276 ACD
GH16H068263 1.4 ENCODE dbSUPER 19.4 -295.4 -295392 3 HDGF PKNOX1 FOXA2 MLX ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 PRMT7 ZFP90 CTCF SNTB2 ZDHHC1 SLC12A4 SLC7A6 LOC100131303 RNU4-36P ENSG00000265113
GH16H067992 1.6 FANTOM5 ENCODE dbSUPER 12.1 -25.3 -25278 4 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZNF143 ZNF207 SP3 PRMT7 EDC4 ACD CENPT CTCF ENSG00000263276 DDX28 E2F4 KIAA0895L SLC7A6OS
GH16H066996 1.8 FANTOM5 Ensembl ENCODE dbSUPER 10.3 +972.5 972526 1 ELF3 FOXA2 MLX ZSCAN4 ZSCAN9 RARA YY1 SLC30A9 HSF1 FOS E2F4 SLC12A4 ATP6V0D1 CES4A DYNC1LI2 CA7 CMTM4 HSF4 GC16P067006 GC16P066989
GH16H067854 1.7 FANTOM5 Ensembl ENCODE 10.4 +112.4 112426 4 PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 YY1 TCF12 ZNF121 ZNF143 RANBP10 ACD NFATC3 NRN1L TSNAXIP1 DUS2 PSKH1 E2F4 SLC12A4 PARD6A
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SLC12A4 on UCSC Golden Path with GeneCards custom track

Promoters for SLC12A4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000087209 1001 2001 HDGF ARNT ARID4B SIN3A DMAP1 SLC30A9 ZNF766 ZNF143 SP3 SP5

Genomic Location for SLC12A4 Gene

Chromosome:
16
Start:
67,943,474 bp from pter
End:
67,969,601 bp from pter
Size:
26,128 bases
Orientation:
Minus strand

Genomic View for SLC12A4 Gene

Genes around SLC12A4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC12A4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC12A4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC12A4 Gene

Proteins for SLC12A4 Gene

  • Protein details for SLC12A4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UP95-S12A4_HUMAN
    Recommended name:
    Solute carrier family 12 member 4
    Protein Accession:
    Q9UP95
    Secondary Accessions:
    • B4DF69
    • B4DR04
    • B4DZ82
    • B7ZAV0
    • F5H066
    • F5H0S9
    • F5H3C0
    • O60632
    • O75893
    • Q13953
    • Q96LD5

    Protein attributes for SLC12A4 Gene

    Size:
    1085 amino acids
    Molecular mass:
    120650 Da
    Quaternary structure:
    • Homomultimer and heteromultimer with other K-Cl cotransporters.
    SequenceCaution:
    • Sequence=AAC35282.1; Type=Frameshift; Positions=454; Evidence={ECO:0000305}; Sequence=BAG57330.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for SLC12A4 Gene

neXtProt entry for SLC12A4 Gene

Post-translational modifications for SLC12A4 Gene

  • N-glycosylated.
  • Ubiquitination at isoforms=2, 3, 4, 5, 6, 785 and isoforms=2, 3, 4, 5, 6, 7707
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SLC12A4 Gene

Domains & Families for SLC12A4 Gene

Gene Families for SLC12A4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • FDA approved drug targets
  • Predicted membrane proteins
  • Transporters

Suggested Antigen Peptide Sequences for SLC12A4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9UP95

UniProtKB/Swiss-Prot:

S12A4_HUMAN :
  • Belongs to the SLC12A transporter family.
Family:
  • Belongs to the SLC12A transporter family.
genes like me logo Genes that share domains with SLC12A4: view

Function for SLC12A4 Gene

Molecular function for SLC12A4 Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by WNK3.
UniProtKB/Swiss-Prot Function:
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.

Phenotypes From GWAS Catalog for SLC12A4 Gene

Gene Ontology (GO) - Molecular Function for SLC12A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0015293 symporter activity IEA --
GO:0015377 cation:chloride symporter activity IEA --
GO:0015379 potassium:chloride symporter activity TAS --
GO:0019901 protein kinase binding IPI 24393035
GO:0022820 potassium ion symporter activity IBA --
genes like me logo Genes that share ontologies with SLC12A4: view
genes like me logo Genes that share phenotypes with SLC12A4: view

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC12A4

CRISPR Products

miRNA for SLC12A4 Gene

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for SLC12A4
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for SLC12A4 Gene

Localization for SLC12A4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC12A4 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 SLC12A4 gene
Compartment Confidence
plasma membrane 5
lysosome 5
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SLC12A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane IDA 17897319
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 8663127
GO:0016020 membrane TAS 8663127
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SLC12A4: view

Pathways & Interactions for SLC12A4 Gene

genes like me logo Genes that share pathways with SLC12A4: view

Gene Ontology (GO) - Biological Process for SLC12A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 8663127
GO:0006811 ion transport TAS --
GO:0006813 potassium ion transport IEA --
GO:0006821 chloride transport IEA --
GO:0006884 cell volume homeostasis TAS 9516379
genes like me logo Genes that share ontologies with SLC12A4: view

No data available for SIGNOR curated interactions for SLC12A4 Gene

Drugs & Compounds for SLC12A4 Gene

(7) Drugs for SLC12A4 Gene - From: DrugBank, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Bumetanide Approved Pharma Agonist, blocker, Target, inhibitor NKCC cotransporter inhibitor, Na+/2Cl-/K+ (NKCC) symporter inhibitor 17
Potassium Chloride Approved, Withdrawn Pharma Target, Transporter, substrate 0
DIOA Pharma Inhibition, Inhibitor 0

(1) Additional Compounds for SLC12A4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6
genes like me logo Genes that share compounds with SLC12A4: view

Transcripts for SLC12A4 Gene

Unigene Clusters for SLC12A4 Gene

Solute carrier family 12 (potassium/chloride transporters), member 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for SLC12A4
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

Alternative Splicing Database (ASD) splice patterns (SP) for SLC12A4 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b · 3c ^ 4a · 4b · 4c ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b · 8c ^ 9a · 9b · 9c · 9d ^ 10a · 10b ^ 11a · 11b ^
SP1:
SP2: -
SP3: -
SP4: - - - -
SP5: -
SP6:
SP7: - - - - - - - - - - - - - -
SP8: -
SP9: -
SP10:
SP11:
SP12: - - - - - - - - - - - - -
SP13:
SP14:
SP15:
SP16:

ExUns: 12 ^ 13a · 13b · 13c ^ 14a · 14b · 14c · 14d ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^ 23a · 23b ^ 24a · 24b ^ 25a · 25b ^ 26a · 26b
SP1: - -
SP2: -
SP3: -
SP4:
SP5:
SP6: - - - - - -
SP7:
SP8:
SP9: -
SP10:
SP11: - -
SP12:
SP13:
SP14:
SP15: - - - -
SP16:

Relevant External Links for SLC12A4 Gene

GeneLoc Exon Structure for
SLC12A4
ECgene alternative splicing isoforms for
SLC12A4

Expression for SLC12A4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SLC12A4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SLC12A4 Gene

This gene is overexpressed in Placenta (28.8), Adrenal (8.1), Pancreas (7.0), and Prostate (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SLC12A4 Gene



Protein tissue co-expression partners for SLC12A4 Gene

NURSA nuclear receptor signaling pathways regulating expression of SLC12A4 Gene:

SLC12A4

SOURCE GeneReport for Unigene cluster for SLC12A4 Gene:

Hs.10094

mRNA Expression by UniProt/SwissProt for SLC12A4 Gene:

Q9UP95-S12A4_HUMAN
Tissue specificity: Ubiquitous. Levels are much higher in erythrocytes from patients with Hb SC and Hb SS compared to normal AA erythrocytes. This may contribute to red blood cell dehydration and to the manifestation of sickle cell disease by increasing the intracellular concentration of HbS. Isoform 1 was not detected in circulating reticulocytes.

Evidence on tissue expression from TISSUES for SLC12A4 Gene

  • Nervous system(4.9)
  • Eye(4.5)
  • Liver(4.2)
  • Kidney(2)
  • Muscle(2)
genes like me logo Genes that share expression patterns with SLC12A4: view

Primer Products

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC12A4 Gene

Orthologs for SLC12A4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC12A4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC12A4 33 34
  • 97.41 (n)
dog
(Canis familiaris)
Mammalia SLC12A4 33 34
  • 91.37 (n)
cow
(Bos Taurus)
Mammalia SLC12A4 33 34
  • 91.06 (n)
mouse
(Mus musculus)
Mammalia Slc12a4 33 16 34
  • 89.16 (n)
rat
(Rattus norvegicus)
Mammalia Slc12a4 33
  • 89 (n)
oppossum
(Monodelphis domestica)
Mammalia SLC12A4 34
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC12A4 34
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves SLC12A4 33 34
  • 73.36 (n)
lizard
(Anolis carolinensis)
Reptilia SLC12A4 34
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100493471 33
  • 71.32 (n)
zebrafish
(Danio rerio)
Actinopterygii slc12a4 33 34
  • 72.6 (n)
Dr.20057 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1702 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011498 33
  • 63.96 (n)
fruit fly
(Drosophila melanogaster)
Insecta kcc 33 34
  • 59.49 (n)
worm
(Caenorhabditis elegans)
Secernentea kcc-2 33 34
  • 52.78 (n)
H16O14.1 35
  • 48 (a)
R13A1.2 35
  • 43 (a)
K02A2.3 35
  • 38 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2084 34
  • 55 (a)
OneToMany
Species where no ortholog for SLC12A4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • wheat (Triticum aestivum)

Evolution for SLC12A4 Gene

ENSEMBL:
Gene Tree for SLC12A4 (if available)
TreeFam:
Gene Tree for SLC12A4 (if available)

Paralogs for SLC12A4 Gene

Paralogs for SLC12A4 Gene

genes like me logo Genes that share paralogs with SLC12A4: view

Variants for SLC12A4 Gene

Sequence variations from dbSNP and Humsavar for SLC12A4 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type
rs121908051 Pathogenic 67,944,001(-) CCCCC(C/T)GCACA reference, missense, utr-variant-3-prime
rs556480808 Uncertain significance 67,943,208(+) CAGCC(A/G)GGCAC downstream-variant-500B, reference, synonymous-codon
rs1000163789 -- 67,965,712(+) TGTAA(A/T)TGGTC intron-variant, upstream-variant-2KB
rs1000217069 -- 67,957,150(+) AGTGC(C/T)CACCA intron-variant
rs1000369222 -- 67,959,517(+) GACCT(A/G)TGAGC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SLC12A4 Gene

Variant ID Type Subtype PubMed ID
nsv476694 CNV novel sequence insertion 20440878
nsv522852 CNV gain 19592680
nsv524363 CNV loss 19592680

Variation tolerance for SLC12A4 Gene

Residual Variation Intolerance Score: 3.44% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.19; 61.92% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SLC12A4 Gene

Human Gene Mutation Database (HGMD)
SLC12A4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC12A4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC12A4 Gene

Disorders for SLC12A4 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SLC12A4 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
agenesis of the corpus callosum with peripheral neuropathy
  • hereditary motor and sensory neuropathy with agenesis of the corpus callosum
sickle cell disease
  • hbs disease
chronic cervicitis
corneal dystrophy, schnyder type
  • schnyder corneal dystrophy
cervix disease
  • cervix disorders
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for SLC12A4

Genetic Association Database (GAD)
SLC12A4
Human Genome Epidemiology (HuGE) Navigator
SLC12A4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SLC12A4
genes like me logo Genes that share disorders with SLC12A4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SLC12A4 Gene

Publications for SLC12A4 Gene

  1. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. (PMID: 8663127) Gillen CM … Forbush B (The Journal of biological chemistry 1996) 2 3 4 22 60
  2. Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation. (PMID: 10564083) Su W … Alper SL (The American journal of physiology 1999) 3 4 22 60
  3. Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells. (PMID: 9516379) Pellegrino CM … Schwartz RS (Blood cells, molecules & diseases 1998) 3 4 22 60
  4. Similar effects of all WNK3 variants on SLC12 cotransporters. (PMID: 21613606) Cruz-Rangel S … Mercado A (American journal of physiology. Cell physiology 2011) 3 4 60
  5. Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol? (PMID: 20602615) Ruaño G … Wu AH (Pharmacogenomics 2010) 3 45 60

Products for SLC12A4 Gene

Sources for SLC12A4 Gene

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