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Aliases for SLC12A6 Gene

Aliases for SLC12A6 Gene

  • Solute Carrier Family 12 Member 6 2 3 5
  • Solute Carrier Family 12 (Potassium/Chloride Transporter), Member 6 2 3
  • Electroneutral Potassium-Chloride Cotransporter 3 3 4
  • K-Cl Cotransporter 3 3 4
  • KCC3 3 4
  • Agenesis Of Corpus Callosum And Peripheral Neuropathy (Andermann Syndrome) 2
  • Solute Carrier Family 12 (Potassium/Chloride Transporters), Member 6 3
  • Potassium Chloride Cotransporter KCC3a-S3 3
  • Potassium Chloride Cotransporter 3 3
  • Potassium-Chloride Transporter-3a 3
  • Potassium-Chloride Transporter-3b 3
  • EC 61
  • EC 61
  • KCC3A 3
  • KCC3B 3
  • ACCPN 3

External Ids for SLC12A6 Gene

Previous HGNC Symbols for SLC12A6 Gene

  • KCC3

Previous GeneCards Identifiers for SLC12A6 Gene

  • GC15M029805
  • GC15M027241
  • GC15M032104
  • GC15M032241
  • GC15M032312
  • GC15M034522
  • GC15M011385

Summaries for SLC12A6 Gene

Entrez Gene Summary for SLC12A6 Gene

  • This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

GeneCards Summary for SLC12A6 Gene

SLC12A6 (Solute Carrier Family 12 Member 6) is a Protein Coding gene. Diseases associated with SLC12A6 include Agenesis Of The Corpus Callosum With Peripheral Neuropathy and Motor Peripheral Neuropathy. 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 SLC12A4.

UniProtKB/Swiss-Prot for SLC12A6 Gene

  • Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells.

Gene Wiki entry for SLC12A6 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC12A6 Gene

Genomics for SLC12A6 Gene

Regulatory Elements for SLC12A6 Gene

Enhancers for SLC12A6 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
GH15G034317 1.3 ENCODE dbSUPER 18.4 +19.3 19266 3.9 PKNOX1 ATF1 MLX ARID4B SIN3A DMAP1 YY1 TCF12 GATA2 SP5 NOP10 SLC12A6 EMC4 ENSG00000207091
GH15G034303 0.6 dbSUPER 30.2 +32.9 32861 4.2 SOX5 SOX13 FOXA2 CEBPG ATF2 MAFK NOP10 SLC12A6 NUTM1 KATNBL1 EMC4 GC15P034315 ENSG00000259468
GH15G034331 2 FANTOM5 Ensembl ENCODE dbSUPER 6.4 +2.8 2825 8.1 PKNOX1 FOXA2 CREB3L1 ARNT AGO1 ARID4B SIN3A FEZF1 ZNF766 ZNF207 NOP10 SLC12A6 ENSG00000207091
GH15G034223 1.1 ENCODE 11 +113.2 113160 2.5 HDGF PKNOX1 CREB3L1 ARNT WRNIP1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 NOP10 AQR HNRNPLP2 SLC12A6 NUTM1 ENSG00000259287 ENSG00000259336 KATNBL1 EMC4
GH15G034238 1 Ensembl ENCODE 11.5 +97.9 97864 4.3 CTCF JUN TRIM22 REST EP300 RAD21 FOSL1 MAFF JUND ZNF316 NOP10 KATNBL1 SLC12A6 NUTM1 ENSG00000259468 EMC4
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SLC12A6 on UCSC Golden Path with GeneCards custom track

Promoters for SLC12A6 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000074788 464 1601 ATF1 FOXA2 CREB3L1 AGO1 ARID4B SIN3A ZNF766 GATA2 ZNF207 ZNF143

Genomic Location for SLC12A6 Gene

34,229,996 bp from pter
34,338,064 bp from pter
108,069 bases
Minus strand

Genomic View for SLC12A6 Gene

Genes around SLC12A6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC12A6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC12A6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC12A6 Gene

Proteins for SLC12A6 Gene

  • Protein details for SLC12A6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Solute carrier family 12 member 6
    Protein Accession:
    Secondary Accessions:
    • A0AV76
    • Q2VI00
    • Q7Z2E7
    • Q7Z4G5
    • Q8TDD4
    • Q9UFR2
    • Q9Y642
    • Q9Y665

    Protein attributes for SLC12A6 Gene

    1150 amino acids
    Molecular mass:
    127617 Da
    Quaternary structure:
    • Homomultimer and heteromultimer with other K-Cl cotransporters.

    Alternative splice isoforms for SLC12A6 Gene

neXtProt entry for SLC12A6 Gene

Selected DME Specific Peptides for SLC12A6 Gene


Post-translational modifications for SLC12A6 Gene

  • N-glycosylated.
  • Glycosylation at isoforms=2, 3, 4, 5, 6379, Asn398, isoforms=2, 3, 4, 5, 6411, and isoforms=2, 3, 4, 5, 6428
  • Modification sites at PhosphoSitePlus

Domains & Families for SLC12A6 Gene

Gene Families for SLC12A6 Gene

Protein Domains for SLC12A6 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the SLC12A transporter family.
  • Belongs to the SLC12A transporter family.
genes like me logo Genes that share domains with SLC12A6: view

Function for SLC12A6 Gene

Molecular function for SLC12A6 Gene

GENATLAS Biochemistry:
solute carrier family 12 (sodium/potassium/chloride cotransporter),highly expressed in brain,heart,skeletal muscle and kidney,upregulated in vascular endothelial cells by VEGF and decreased by TNF
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=10.7 mM for extracellular Rb(+) (isoform 1) {ECO:0000269 PubMed:16048901}; KM=7.3 mM for extracellular Cl(-) (isoform 1) {ECO:0000269 PubMed:16048901}; KM=17.2 mM for extracellular Rb(+) (isoform 2) {ECO:0000269 PubMed:16048901}; KM=8.2 mM for extracellular Cl(-) (isoform 2) {ECO:0000269 PubMed:16048901};
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by N-ethylmaleimide (NEM). Inhibited by DIOA, bumetanide and furosemide. Inhibited by WNK3.
UniProtKB/Swiss-Prot Function:
Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells.
UniProtKB/Swiss-Prot Induction:
Up-regulated by VEGF. Down-regulated by TNF.

Enzyme Numbers (IUBMB) for SLC12A6 Gene

Gene Ontology (GO) - Molecular Function for SLC12A6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005215 transporter activity IEA --
GO:0015293 symporter activity IEA --
GO:0015377 cation:chloride symporter activity IEA --
GO:0015379 potassium:chloride symporter activity TAS,IEA --
GO:0022820 potassium ion symporter activity IBA --
genes like me logo Genes that share ontologies with SLC12A6: view
genes like me logo Genes that share phenotypes with SLC12A6: view

Human Phenotype Ontology for SLC12A6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC12A6 Gene

MGI Knock Outs for SLC12A6:

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC12A6

CRISPR Products

miRNA for SLC12A6 Gene

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for SLC12A6 Gene

Localization for SLC12A6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC12A6 Gene

Basolateral cell membrane; Multi-pass membrane protein.

Subcellular locations from

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 SLC12A6 gene
Compartment Confidence
plasma membrane 5
cytosol 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for SLC12A6 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 NAS,IEA 10187864
GO:0016323 basolateral plasma membrane ISS --
genes like me logo Genes that share ontologies with SLC12A6: view

Pathways & Interactions for SLC12A6 Gene

genes like me logo Genes that share pathways with SLC12A6: view

SIGNOR curated interactions for SLC12A6 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for SLC12A6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis NAS 10187864
GO:0006810 transport IEA --
GO:0006811 ion transport IEA,TAS --
GO:0006813 potassium ion transport IEA --
GO:0007268 chemical synaptic transmission IBA --
genes like me logo Genes that share ontologies with SLC12A6: view

Drugs & Compounds for SLC12A6 Gene

(4) Drugs for SLC12A6 Gene - From: DrugBank, DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Potassium Chloride Approved, Withdrawn Pharma Target, Transporter, substrate 0
DIOA Pharma Inhibition, Inhibitor 0

(2) Additional Compounds for SLC12A6 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
genes like me logo Genes that share compounds with SLC12A6: view

Transcripts for SLC12A6 Gene

Unigene Clusters for SLC12A6 Gene

Solute carrier family 12 (potassium/chloride transporters), member 6:
Representative Sequences:

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC12A6 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3a · 3b · 3c · 3d ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a ·
SP1: - - - - - - - -
SP2: - - - - -
SP3: - - - - -
SP4: -
SP5: - -
SP6: - - -
SP7: -
SP8: - - - - - -
SP9: - - - - - - -
SP10: - - - - - -

ExUns: 18b ^ 19 ^ 20 ^ 21a · 21b ^ 22a · 22b ^ 23 ^ 24a · 24b · 24c ^ 25a · 25b · 25c ^ 26 ^ 27 ^ 28 ^ 29a · 29b
SP1: - - - -
SP2: - - - -
SP3: - - -
SP4: - - - -
SP5: - - - -
SP6: - - - -
SP7: - - - -
SP12: -

Relevant External Links for SLC12A6 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for SLC12A6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SLC12A6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC12A6 Gene

This gene is overexpressed in Whole Blood (x5.3).

Protein differential expression in normal tissues from HIPED for SLC12A6 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (15.5), Plasma (14.8), and Lymph node (8.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SLC12A6 Gene

NURSA nuclear receptor signaling pathways regulating expression of SLC12A6 Gene:


SOURCE GeneReport for Unigene cluster for SLC12A6 Gene:


mRNA Expression by UniProt/SwissProt for SLC12A6 Gene:

Tissue specificity: Highly expressed in heart, brain and kidney. Detected at lower levels in skeletal muscle, placenta, lung and pancreas. Detected in umbilical vein endothelial cells. Isoform 2 is more abundant in kidney. Isoform 5 is testis specific. Expressed in the proximal tubule of the kidney (at protein level).

Evidence on tissue expression from TISSUES for SLC12A6 Gene

  • Nervous system(4.6)
  • Kidney(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC12A6 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cheek
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • nose
  • outer ear
  • scalp
  • skull
  • bronchus
  • lung
  • rib
  • rib cage
  • pelvis
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
  • blood
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with SLC12A6: view

Primer Products

No data available for Protein tissue co-expression partners for SLC12A6 Gene

Orthologs for SLC12A6 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC12A6 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SLC12A6 34 35
  • 99.83 (n)
(Mus musculus)
Mammalia Gm21985 35
  • 98 (a)
Slc12a6 34 16 35
  • 90.61 (n)
(Monodelphis domestica)
Mammalia SLC12A6 35
  • 97 (a)
(Ornithorhynchus anatinus)
Mammalia SLC12A6 35
  • 94 (a)
(Bos Taurus)
Mammalia SLC12A6 34 35
  • 92.78 (n)
(Canis familiaris)
Mammalia SLC12A6 34 35
  • 92.75 (n)
(Rattus norvegicus)
Mammalia Slc12a6 34
  • 91.07 (n)
(Anolis carolinensis)
Reptilia SLC12A6 35
  • 90 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a6 34
  • 72.13 (n)
Str.7199 34
African clawed frog
(Xenopus laevis)
Amphibia LOC398663 34
(Danio rerio)
Actinopterygii SLC12A6 (2 of 2) 35
  • 83 (a)
slc12a7b 34
  • 67.54 (n)
SLC12A6 (1 of 2) 35
  • 62 (a)
fruit fly
(Drosophila melanogaster)
Insecta kcc 35
  • 56 (a)
(Caenorhabditis elegans)
Secernentea H16O14.1 36
  • 48 (a)
kcc-2 35
  • 46 (a)
R13A1.2 36
  • 44 (a)
K02A2.3 36
  • 37 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2084 35
  • 55 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10069 34
Species where no ortholog for SLC12A6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • chicken (Gallus gallus)
  • 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 (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 SLC12A6 Gene

Gene Tree for SLC12A6 (if available)
Gene Tree for SLC12A6 (if available)

Paralogs for SLC12A6 Gene

Paralogs for SLC12A6 Gene

genes like me logo Genes that share paralogs with SLC12A6: view

Variants for SLC12A6 Gene

Sequence variations from dbSNP and Humsavar for SLC12A6 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type
rs1057518713 Pathogenic 34,336,430(-) TTCTC(-/C)ACCCC nc-transcript-variant, reference, frameshift-variant
rs121908427 Pathogenic 34,236,719(-) CAGAG(A/C/T)GAGAC nc-transcript-variant, reference, synonymous-codon, stop-gained
rs121908428 Pathogenic 34,243,993(-) GACCC(C/T)GATTC nc-transcript-variant, reference, stop-gained
rs121908429 Pathogenic 34,257,713(-) TTTTA(C/T)GCCTT intron-variant, nc-transcript-variant, reference, missense
rs199747285 Pathogenic 34,260,958(+) ATATT(A/C)ATCTC nc-transcript-variant, reference, stop-gained

Structural Variations from Database of Genomic Variants (DGV) for SLC12A6 Gene

Variant ID Type Subtype PubMed ID
dgv4456n54 CNV gain 21841781
dgv448e214 CNV loss 21293372
esv2659969 CNV deletion 23128226
esv2662279 CNV deletion 23128226
esv2760024 CNV gain+loss 17122850
esv33337 CNV gain+loss 17666407
esv3569431 CNV gain 25503493
esv3636106 CNV gain 21293372
esv3636108 CNV loss 21293372
esv3636110 CNV loss 21293372
nsv1051403 CNV loss 25217958
nsv1052620 CNV gain 25217958
nsv1127423 CNV deletion 24896259
nsv1127424 CNV deletion 24896259
nsv1138354 CNV deletion 24896259
nsv428303 CNV gain 18775914
nsv469547 CNV loss 16826518
nsv471682 CNV gain+loss 15918152
nsv472676 CNV novel sequence insertion 20440878
nsv819906 CNV loss 19587683

Variation tolerance for SLC12A6 Gene

Residual Variation Intolerance Score: 1.73% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.82; 34.25% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SLC12A6 Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC12A6 Gene

Disorders for SLC12A6 Gene

MalaCards: The human disease database

(8) MalaCards diseases for SLC12A6 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, 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
motor peripheral neuropathy
  • hereditary motor and sensory neuropathy
  • peripheral neuropathy
epilepsy, generalized, with febrile seizures plus, type 5
  • epilepsy, idiopathic generalized, 10
sensory peripheral neuropathy
  • peripheral sensory neuropathy
- elite association - COSMIC cancer census association via MalaCards


  • Agenesis of the corpus callosum, with peripheral neuropathy (ACCPN) [MIM:218000]: A disease that is characterized by severe progressive sensorimotor neuropathy, mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SLC12A6

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with SLC12A6: view

No data available for Genatlas for SLC12A6 Gene

Publications for SLC12A6 Gene

  1. The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum. (PMID: 12368912) Howard H.C. … Rouleau G.A. (Nat. Genet. 2002) 3 4 22 46 64
  2. Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter. (PMID: 10187864) Hiki K. … Gamble J.R. (J. Biol. Chem. 1999) 2 3 4 22 64
  3. Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family. (PMID: 10347194) Mount D.B. … Gamba G. (J. Biol. Chem. 1999) 2 3 4 22 64
  4. NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter. (PMID: 16048901) Mercado A. … Mount D.B. (Am. J. Physiol. 2005) 3 4 22 64
  5. Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter. (PMID: 10600773) Race J.E. … Holtzman E.J. (Am. J. Physiol. 1999) 3 4 22 64

Products for SLC12A6 Gene

Sources for SLC12A6 Gene

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