Seroatlas · Human Serome Atlas

SLC12A1

Solute carrier family 12 member 1

Also known as: BSC, BSC-1, BSC1, CCC2, NKCC2, S12A1_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q13621
Gene: SLC12A1
Ensembl: ENSG00000074803
Chromosome: 15
Canonical length: 1099 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted membrane proteins, Transporters
Subcellular location: Nucleoplasm,Vesicles

OverviewNCBI Gene

This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

1099 residues, UniProt reviewed canonical sequence.

>Q13621|SLC12A1
     1  MSLNNSSNVF LDSVPSNTNR FQVSVINENH ESSAAADDNT DPPHYEETSF GDEAQKRLRI
    61  SFRPGNQECY DNFLQSGETA KTDASFHAYD SHTNTYYLQT FGHNTMDAVP KIEYYRNTGS
   121  ISGPKVNRPS LLEIHEQLAK NVAVTPSSAD RVANGDGIPG DEQAENKEDD QAGVVKFGWV
   181  KGVLVRCMLN IWGVMLFIRL SWIVGEAGIG LGVLIILLST MVTSITGLST SAIATNGFVR
   241  GGGAYYLISR SLGPEFGGSI GLIFAFANAV AVAMYVVGFA ETVVDLLKES DSMMVDPTND
   301  IRIIGSITVV ILLGISVAGM EWEAKAQVIL LVILLIAIAN FFIGTVIPSN NEKKSRGFFN
   361  YQASIFAENF GPRFTKGEGF FSVFAIFFPA ATGILAGANI SGDLEDPQDA IPRGTMLAIF
   421  ITTVAYLGVA ICVGACVVRD ATGNMNDTII SGMNCNGSAA CGLGYDFSRC RHEPCQYGLM
   481  NNFQVMSMVS GFGPLITAGI FSATLSSALA SLVSAPKVFQ ALCKDNIYKA LQFFAKGYGK
   541  NNEPLRGYIL TFLIAMAFIL IAELNTIAPI ISNFFLASYA LINFSCFHAS YAKSPGWRPA
   601  YGIYNMWVSL FGAVLCCAVM FVINWWAAVI TYVIEFFLYV YVTCKKPDVN WGSSTQALSY
   661  VSALDNALEL TTVEDHVKNF RPQCIVLTGG PMTRPALLDI THAFTKNSGL CICCEVFVGP
   721  RKLCVKEMNS GMAKKQAWLI KNKIKAFYAA VAADCFRDGV RSLLQASGLG RMKPNTLVIG
   781  YKKNWRKAPL TEIENYVGII HDAFDFEIGV VIVRISQGFD ISQVLQVQEE LERLEQERLA
   841  LEATIKDNEC EEESGGIRGL FKKAGKLNIT KTTPKKDGSI NTSQSMHVGE FNQKLVEAST
   901  QFKKKQEKGT IDVWWLFDDG GLTLLIPYIL TLRKKWKDCK LRIYVGGKIN RIEEEKIVMA
   961  SLLSKFRIKF ADIHIIGDIN IRPNKESWKV FEEMIEPYRL HESCKDLTTA EKLKRETPWK
  1021  ITDAELEAVK EKSYRQVRLN ELLQEHSRAA NLIVLSLPVA RKGSISDLLY MAWLEILTKN
  1081  LPPVLLVRGN HKNVLTFYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC12A1 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): 0.32
Highest tissue expression: 664 nTPM

Expression across tissuesHPA

Tissue

kidney: 664 nTPM
cerebral cortex: 0.8 nTPM
testis: 0.7 nTPM
basal ganglia: 0.4 nTPM
cerebellum: 0.4 nTPM
hypothalamus: 0.4 nTPM

Single-cell type

loop of henle epithelial cells: 3,068 nCPM
renal collecting duct intercalated cells: 103 nCPM
proximal tubule cells: 85 nCPM
podocytes: 83 nCPM
distal convoluted tubule cells: 78 nCPM
renal connecting tubule cells: 67 nCPM

Immune cell

neutrophil: 0.2 nTPM
basophil: 0.1 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM

Brain region

hypothalamus: 2.3 nTPM
midbrain: 2.1 nTPM
cerebellum: 2 nTPM
medulla oblongata: 2 nTPM
cerebral cortex: 1.9 nTPM
pons: 1.9 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC12A1.

Disease | AllUniProt

Conditions SLC12A1 is implicated in, by any mechanism.

Bartter syndrome 1, antenatal (BARTS1) MIM:601678

Disease | GeneticClinVar

133 pathogenic / likely-pathogenic of 1,098 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Bartter disease type 1
Bartter syndrome
SLC12A1-related disorder
Nephrocalcinosis
Kidney stone

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): 0.82
gnomAD pLI: 0
gnomAD missense Z: 1.16
DepMap mean gene effect: -0.11
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

sodium:potassium:chloride symporter activity
sodium:ammonium:chloride symporter activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SLC12A1 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 SLC12A1 as an antibody target. Whether an autoantibody or antibody against SLC12A1 could matter depends on whether native SLC12A1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SLC12A1 is annotated at the cell surface, where native SLC12A1 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 SLC12A1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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