Free for academic non-profit institutions. Other users need a Commercial license

Aliases for SLC12A5 Gene

Aliases for SLC12A5 Gene

  • Solute Carrier Family 12 Member 5 2 3 5
  • Solute Carrier Family 12 (Potassium/Chloride Transporter), Member 5 2 3
  • Electroneutral Potassium-Chloride Cotransporter 2 3 4
  • Neuronal K-Cl Cotransporter 3 4
  • K-Cl Cotransporter 2 3 4
  • HKCC2 3 4
  • KCC2 3 4
  • Erythroid K-Cl Cotransporter 2 3
  • KIAA1176 4
  • EIEE34 3
  • EIG14 3

External Ids for SLC12A5 Gene

Previous GeneCards Identifiers for SLC12A5 Gene

  • GC20P044386
  • GC20P045296
  • GC20P045343
  • GC20P044091
  • GC20P044651
  • GC20P041391

Summaries for SLC12A5 Gene

Entrez Gene Summary for SLC12A5 Gene

  • K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

GeneCards Summary for SLC12A5 Gene

SLC12A5 (Solute Carrier Family 12 Member 5) is a Protein Coding gene. Diseases associated with SLC12A5 include Epileptic Encephalopathy, Early Infantile, 34 and Epilepsy, Idiopathic Generalized 14. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Circadian entrainment. GO annotations related to this gene include protein kinase binding and potassium:chloride symporter activity. An important paralog of this gene is SLC12A7.

UniProtKB/Swiss-Prot for SLC12A5 Gene

  • Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis. As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262).

Tocris Summary for SLC12A5 Gene

  • K+/Cl- cotransporter 2 (KCC2, SLC12A5) is a neuron specific membrane protein that is responsible for the maintenance of the low intracellular Cl- concentration in adult neurons and has a key role in GABAA and glycine signaling.

Gene Wiki entry for SLC12A5 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC12A5 Gene

Genomics for SLC12A5 Gene

Regulatory Elements for SLC12A5 Gene

Enhancers for SLC12A5 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
GH20F045997 1.3 FANTOM5 Ensembl ENCODE 20.1 -22.3 -22290 4.8 PKNOX1 ZFP64 ZBTB11 ZEB2 ZNF623 ZNF781 ZNF518A NR2F2 ZNF264 SMARCA4 NCOA5 CD40 ZNF335 TP53RK SLC12A5 WFDC3 ENSG00000204044 PCIF1 DNTTIP1 ENSG00000271984
GH20F046002 0.9 FANTOM5 Ensembl ENCODE 13.1 -12.9 -12890 12.0 HDGF PKNOX1 CREB3L1 ARID4B DMAP1 ZNF2 ZNF143 ZNF263 SP3 SP5 CD40 SLC12A5 NCOA5 ZNF335 PCIF1 PLTP MMP9 FTLP1
GH20F046021 0.8 ENCODE 13 -0.2 -203 0.8 CBX3 PKNOX1 ATF1 KLF17 ARID4B DEAF1 ZNF48 ZNF2 RAD21 GLIS2 SLC12A5 MMP9
GH20F046061 0.2 Ensembl 11.8 +39.2 39211 0.6 ZIC2 GABPA ZFHX2 IKZF1 GLIS1 PBX2 SPI1 SP7 ENSG00000204044 SLC12A5 NCOA5 LOC105372632
GH20F046070 0.2 ENCODE 11.7 +49.0 48976 0.8 ZNF362 BHLHE40 MAFG ZNF384 ZNF316 POLR2A NFE2 FOS PRDM1 MAFK SLC12A5 ENSG00000204044 NCOA5 LOC105372632
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around SLC12A5 on UCSC Golden Path with GeneCards custom track

Promoters for SLC12A5 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000401721 510 1601 PKNOX1 ATF1 ARID4B ZNF48 ZNF2 GLIS2 ZNF143 ZNF263 SP3 MIER2

Genomic Location for SLC12A5 Gene

Chromosome:
20
Start:
46,021,690 bp from pter
End:
46,060,152 bp from pter
Size:
38,463 bases
Orientation:
Plus strand

Genomic View for SLC12A5 Gene

Genes around SLC12A5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC12A5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC12A5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC12A5 Gene

Proteins for SLC12A5 Gene

  • Protein details for SLC12A5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H2X9-S12A5_HUMAN
    Recommended name:
    Solute carrier family 12 member 5
    Protein Accession:
    Q9H2X9
    Secondary Accessions:
    • A2RTX2
    • Q5VZ41
    • Q9H4Z0
    • Q9ULP4

    Protein attributes for SLC12A5 Gene

    Size:
    1139 amino acids
    Molecular mass:
    126184 Da
    Quaternary structure:
    • Homomultimer and heteromultimer with other K-Cl cotransporters. Interacts with AP2A1 (By similarity).
    Miscellaneous:
    • Inhibited by furosemide and bumetanide.

    Alternative splice isoforms for SLC12A5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC12A5 Gene

Post-translational modifications for SLC12A5 Gene

  • Glycosylation at Asn 442 and Asn 833
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for SLC12A5 (KCC2/SLC12A5)
  • Cell Signaling Technology (CST) Antibodies for SLC12A5 (KCC2)

No data available for DME Specific Peptides for SLC12A5 Gene

Domains & Families for SLC12A5 Gene

Gene Families for SLC12A5 Gene

Protein Domains for SLC12A5 Gene

Suggested Antigen Peptide Sequences for SLC12A5 Gene

Graphical View of Domain Structure for InterPro Entry

Q9H2X9

UniProtKB/Swiss-Prot:

S12A5_HUMAN :
  • Belongs to the SLC12A transporter family.
Family:
  • Belongs to the SLC12A transporter family.
genes like me logo Genes that share domains with SLC12A5: view

Function for SLC12A5 Gene

Molecular function for SLC12A5 Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by WNK3.
UniProtKB/Swiss-Prot Function:
Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis. As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262).

Gene Ontology (GO) - Molecular Function for SLC12A5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0015108 chloride transmembrane transporter activity IDA 26333769
GO:0015293 symporter activity IEA --
GO:0015377 cation:chloride symporter activity IEA --
GO:0015379 potassium:chloride symporter activity IEA,TAS --
GO:0022820 potassium ion symporter activity IBA --
genes like me logo Genes that share ontologies with SLC12A5: view
genes like me logo Genes that share phenotypes with SLC12A5: view

Human Phenotype Ontology for SLC12A5 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC12A5 Gene

MGI Knock Outs for SLC12A5:

Animal Model Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SLC12A5 Gene

Localization for SLC12A5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC12A5 Gene

Membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SLC12A5 Gene COMPARTMENTS Subcellular localization image for SLC12A5 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 1
extracellular 1
nucleus 1

Gene Ontology (GO) - Cellular Components for SLC12A5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA,NAS 12106695
GO:0043025 neuronal cell body IEA --
genes like me logo Genes that share ontologies with SLC12A5: view

Pathways & Interactions for SLC12A5 Gene

genes like me logo Genes that share pathways with SLC12A5: view

Pathways by source for SLC12A5 Gene

Interacting Proteins for SLC12A5 Gene

Gene Ontology (GO) - Biological Process for SLC12A5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA,NAS 12106695
GO:0006811 ion transport IEA,TAS --
GO:0006813 potassium ion transport IEA --
GO:0006821 chloride transport IEA --
GO:0006873 cellular ion homeostasis NAS 12106695
genes like me logo Genes that share ontologies with SLC12A5: view

No data available for SIGNOR curated interactions for SLC12A5 Gene

Drugs & Compounds for SLC12A5 Gene

(10) Drugs for SLC12A5 Gene - From: DrugBank, ApexBio, 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 16
Potassium Chloride Approved, Withdrawn Pharma Target, Transporter, substrate 0
Furosemide Approved, Vet_approved Pharma Agonist GABAA receptors antagonist, Na+/2Cl-/K+ (NKCC) symporter inhibitor. Also antagonizes GABAA 188
DIOA Pharma Inhibition, Inhibitor 0
VU0240551 Pharma Inhibition, Inhibitor 0

(4) Additional Compounds for SLC12A5 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6

(1) ApexBio Compounds for SLC12A5 Gene

Compound Action Cas Number
VU 0240551 KCC2 inhibitor 893990-34-6
genes like me logo Genes that share compounds with SLC12A5: view

Transcripts for SLC12A5 Gene

Unigene Clusters for SLC12A5 Gene

Solute carrier family 12 (potassium/chloride transporter), member 5:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC12A5 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^
SP1: - -
SP2: -
SP3: - - -
SP4:
SP5:
SP6:

ExUns: 23a · 23b ^ 24a · 24b ^ 25 ^ 26
SP1: -
SP2:
SP3:
SP4:
SP5:
SP6:

Relevant External Links for SLC12A5 Gene

GeneLoc Exon Structure for
SLC12A5
ECgene alternative splicing isoforms for
SLC12A5

Expression for SLC12A5 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SLC12A5 Gene

mRNA differential expression in normal tissues according to GTEx for SLC12A5 Gene

This gene is overexpressed in Brain - Cerebellum (x7.3), Brain - Cerebellar Hemisphere (x7.3), Brain - Frontal Cortex (BA9) (x6.5), Brain - Cortex (x5.3), and Brain - Anterior cingulate cortex (BA24) (x5.0).

Protein differential expression in normal tissues from HIPED for SLC12A5 Gene

This gene is overexpressed in Frontal cortex (39.0) and Retina (21.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SLC12A5 Gene



Protein tissue co-expression partners for SLC12A5 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SLC12A5 Gene:

SLC12A5

SOURCE GeneReport for Unigene cluster for SLC12A5 Gene:

Hs.21413

mRNA Expression by UniProt/SwissProt for SLC12A5 Gene:

Q9H2X9-S12A5_HUMAN
Tissue specificity: Brain specific. Detected in neuronal cells.
genes like me logo Genes that share expression patterns with SLC12A5: view

Primer Products

Orthologs for SLC12A5 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SLC12A5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC12A5 34 35
  • 99.03 (n)
oppossum
(Monodelphis domestica)
Mammalia SLC12A5 35
  • 96 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SLC12A5 34 35
  • 93.37 (n)
dog
(Canis familiaris)
Mammalia SLC12A5 34 35
  • 93.3 (n)
mouse
(Mus musculus)
Mammalia Slc12a5 34 16 35
  • 90.91 (n)
rat
(Rattus norvegicus)
Mammalia Slc12a5 34
  • 90.74 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SLC12A5 35
  • 90 (a)
OneToOne
chicken
(Gallus gallus)
Aves SLC12A5 34 35
  • 84.16 (n)
lizard
(Anolis carolinensis)
Reptilia SLC12A5 35
  • 87 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a5 34
  • 75.7 (n)
zebrafish
(Danio rerio)
Actinopterygii slc12a5a 35
  • 78 (a)
OneToMany
LOC572215 34
  • 73.97 (n)
slc12a5b 35
  • 73 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta kcc 35
  • 53 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea H16O14.1 36
  • 45 (a)
R13A1.2 36
  • 44 (a)
kcc-2 35
  • 44 (a)
OneToMany
K02A2.3 36
  • 38 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons CCC1 34
  • 50.25 (n)
rice
(Oryza sativa)
Liliopsida Os08g0323700 34
  • 48.03 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2084 35
  • 53 (a)
OneToMany
Species where no ortholog for SLC12A5 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)
  • rainbow trout (Oncorhynchus mykiss)
  • 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SLC12A5 Gene

ENSEMBL:
Gene Tree for SLC12A5 (if available)
TreeFam:
Gene Tree for SLC12A5 (if available)

Paralogs for SLC12A5 Gene

Variants for SLC12A5 Gene

Sequence variations from dbSNP and Humsavar for SLC12A5 Gene

SNP ID Clin Chr 20 pos Sequence Context AA Info Type
rs142740233 Epilepsy, idiopathic generalized 14 (EIG14) [MIM:616685], other 46,056,217(+) GCTCC(A/G)CCTGA reference, missense
rs548424453 Epilepsy, idiopathic generalized 14 (EIG14) [MIM:616685], other 46,057,189(+) TGCGG(A/C/T)GCATG reference, missense
rs863225304 Epileptic encephalopathy, early infantile, 34 (EIEE34) [MIM:616645], Pathogenic 46,043,294(+) CCTGC(C/T)GGTTG reference, missense
rs863225305 Epileptic encephalopathy, early infantile, 34 (EIEE34) [MIM:616645], Pathogenic 46,045,891(+) CCATG(A/G)CAAGG reference, missense
rs863225306 Epileptic encephalopathy, early infantile, 34 (EIEE34) [MIM:616645], Pathogenic 46,041,337(+) CTGCC(A/T)CCTGG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for SLC12A5 Gene

Variant ID Type Subtype PubMed ID
nsv1063229 CNV gain 25217958
nsv1072117 CNV deletion 25765185
nsv473197 CNV novel sequence insertion 20440878
nsv833991 CNV loss 17160897
nsv954046 CNV deletion 24416366
nsv954047 CNV deletion 24416366

Variation tolerance for SLC12A5 Gene

Residual Variation Intolerance Score: 2.35% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.95; 49.30% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SLC12A5 Gene

Human Gene Mutation Database (HGMD)
SLC12A5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC12A5

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC12A5 Gene

Disorders for SLC12A5 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SLC12A5 Gene - From: ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
epileptic encephalopathy, early infantile, 34
  • eiee34
epilepsy, idiopathic generalized 14
  • eig14
malignant migrating partial seizures of infancy
  • epileptic encephalopathy, early infantile, 14
hypothalamic hamartomas
  • hamartoma of the hypothalamus
epilepsy
  • epilepsy syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

S12A5_HUMAN
  • Epilepsy, idiopathic generalized 14 (EIG14) [MIM:616685]: An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. {ECO:0000269 PubMed:24668262, ECO:0000269 PubMed:24928908, ECO:0000269 PubMed:26528127}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Epileptic encephalopathy, early infantile, 34 (EIEE34) [MIM:616645]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE34 is characterized by onset of refractory migrating focal seizures in infancy. Affected children show developmental regression and are severely impaired globally. {ECO:0000269 PubMed:26333769}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SLC12A5

Genetic Association Database (GAD)
SLC12A5
Human Genome Epidemiology (HuGE) Navigator
SLC12A5
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SLC12A5
genes like me logo Genes that share disorders with SLC12A5: view

No data available for Genatlas for SLC12A5 Gene

Publications for SLC12A5 Gene

  1. Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1. (PMID: 18602983) Bento J.L. … Mychaleckyj J.C. (Genomics 2008) 3 22 46 64
  2. Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. (PMID: 26333769) Stoedberg T. … Kurian M.A. (Nat. Commun. 2015) 3 4 64
  3. A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. (PMID: 24668262) Puskarjov M. … Kaila K. (EMBO Rep. 2014) 3 4 64
  4. Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy. (PMID: 24928908) Kahle K.T. … Rouleau G.A. (EMBO Rep. 2014) 3 4 64
  5. Similar Effects of all WNK3 Variants upon SLC12 Cotransporters. (PMID: 21613606) Cruz-Rangel S. … Mercado A. (Am. J. Physiol. 2011) 3 4 64

Products for SLC12A5 Gene

Sources for SLC12A5 Gene

Content
Loading form....