Seroatlas · Human Serome Atlas

SLC12A6

Solute carrier family 12 member 6

Also known as: ACCPN, KCC3, KCC3A, KCC3B, S12A6_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9UHW9
Gene: SLC12A6
Ensembl: ENSG00000140199
Chromosome: 15
Canonical length: 1150 aa
Protein class: Disease related genes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location: Vesicles,Cytosol
Quaternary structure: Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

1150 residues, UniProt reviewed canonical sequence.

>Q9UHW9|SLC12A6
     1  MHPPETTTKM ASVRFMVTPT KIDDIPGLSD TSPDLSSRSS SRVRFSSRES VPETSRSEPM
    61  SEMSGATTSL ATVALDPPSD RTSHPQDVIE DLSQNSITGE HSQLLDDGHK KARNAYLNNS
   121  NYEEGDEYFD KNLALFEEEM DTRPKVSSLL NRMANYTNLT QGAKEHEEAE NITEGKKKPT
   181  KTPQMGTFMG VYLPCLQNIF GVILFLRLTW VVGTAGVLQA FAIVLICCCC TMLTAISMSA
   241  IATNGVVPAG GSYFMISRAL GPEFGGAVGL CFYLGTTFAA AMYILGAIEI FLVYIVPRAA
   301  IFHSDDALKE SAAMLNNMRV YGTAFLVLMV LVVFIGVRYV NKFASLFLAC VIVSILAIYA
   361  GAIKSSFAPP HFPVCMLGNR TLSSRHIDVC SKTKEINNMT VPSKLWGFFC NSSQFFNATC
   421  DEYFVHNNVT SIQGIPGLAS GIITENLWSN YLPKGEIIEK PSAKSSDVLG SLNHEYVLVD
   481  ITTSFTLLVG IFFPSVTGIM AGSNRSGDLK DAQKSIPIGT ILAILTTSFV YLSNVVLFGA
   541  CIEGVVLRDK FGDAVKGNLV VGTLSWPSPW VIVIGSFFST CGAGLQSLTG APRLLQAIAK
   601  DNIIPFLRVF GHSKANGEPT WALLLTAAIA ELGILIASLD LVAPILSMFF LMCYLFVNLA
   661  CALQTLLRTP NWRPRFRYYH WALSFMGMSI CLALMFISSW YYAIVAMVIA GMIYKYIEYQ
   721  GAEKEWGDGI RGLSLSAARF ALLRLEEGPP HTKNWRPQLL VLLKLDEDLH VKHPRLLTFA
   781  SQLKAGKGLT IVGSVIVGNF LENYGEALAA EQTIKHLMEA EKVKGFCQLV VAAKLREGIS
   841  HLIQSCGLGG MKHNTVVMGW PNGWRQSEDA RAWKTFIGTV RVTTAAHLAL LVAKNISFFP
   901  SNVEQFSEGN IDVWWIVHDG GMLMLLPFLL KQHKVWRKCS IRIFTVAQLE DNSIQMKKDL
   961  ATFLYHLRIE AEVEVVEMHD SDISAYTYER TLMMEQRSQM LRHMRLSKTE RDREAQLVKD
  1021  RNSMLRLTSI GSDEDEETET YQEKVHMTWT KDKYMASRGQ KAKSMEGFQD LLNMRPDQSN
  1081  VRRMHTAVKL NEVIVNKSHE AKLVLLNMPG PPRNPEGDEN YMEFLEVLTE GLERVLLVRG
  1141  GGSEVITIYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC12A6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 9
Mean surface accessibility (rSASA): 0.31
Highest tissue expression: 29 nTPM

Expression across tissuesHPA

Tissue

retina: 29 nTPM
bone marrow: 25 nTPM
testis: 24 nTPM
esophagus: 17 nTPM
vagina: 16 nTPM
kidney: 15 nTPM

Single-cell type

neutrophils: 2,078 nCPM
neutrophil progenitors: 503 nCPM
urothelial cells: 312 nCPM
esophageal apical cells: 300 nCPM
proximal tubule cells: 260 nCPM
rod photoreceptor cells: 219 nCPM

Immune cell

neutrophil: 24 nTPM
basophil: 15 nTPM
T-reg: 3.2 nTPM
eosinophil: 2.6 nTPM
naive B-cell: 2.4 nTPM
intermediate monocyte: 1.8 nTPM

Brain region

pons: 24 nTPM
white matter: 22 nTPM
medulla oblongata: 21 nTPM
thalamus: 21 nTPM
cerebral cortex: 21 nTPM
midbrain: 20 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC12A6.

Disease | AllUniProt

Conditions SLC12A6 is implicated in, by any mechanism.

Agenesis of the corpus callosum, with peripheral neuropathy (ACCPN) MIM:218000
Charcot-Marie-Tooth disease, axonal, type 2II (CMT2II) MIM:620068

Disease | GeneticClinVar

237 pathogenic / likely-pathogenic of 1,794 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Agenesis of the corpus callosum with peripheral neuropathy
Charcot-Marie-Tooth disease, axonal, IIa 2II
Charcot-Marie-Tooth disease
SLC12A6-related disorder
Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.4
gnomAD pLI: 0.01
gnomAD missense Z: 2.96
DepMap mean gene effect: -0.09
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SLC12A6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SLC12A6 as an antibody target. Whether an autoantibody or antibody against SLC12A6 could matter depends on whether native SLC12A6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SLC12A6 is annotated at the cell surface, where native SLC12A6 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SLC12A6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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