Tclin SLC12A1 Solute carrier family 12 member 1

Protein Classes

DTO Classes

Protein / Transporter / Slc Superfamily Of Solute Carriers / Slc12 Family Of Cation-coupled Chloride Transporters / Solute Carrier Family 12 Member 1

Protein Summary

Description

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume. 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]

Uniprot Accession IDs

• Q13621
• A8JYA2
• E9PDW4

Gene Name

• SLC12A1

Ensembl ID

• ENST00000380993
• ENSP00000370381
• ENSG00000074803
• ENST00000396577
• ENSP00000379822
• ENST00000558405
• ENSP00000453409
• ENST00000647232
• ENSP00000493875
• ENST00000647546
• ENSP00000495332

Symbol

• NKCC2
• BSC1
• NKCC2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.73
cell type or tissue	0.67
drug	0.65
biological term	0.6
molecular function	0.6

Related Tools

RESOLUTE

RESOLUTE is a public-private partnership with the goal of escalating research on solute carriers (SLCs) and to establish SLCs as a tractable target class for medical research and development.

Go To Tool

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

Go To Tool

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

Go To Tool

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

Go To Tool

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 319.38   (req: < 5)

Gene RIFs: 36   (req: <= 3)

Antibodies: 230   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 319.38   (req: >= 5)

Gene RIFs: 36   (req: > 3)

Antibodies: 230   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 5

Approved Drugs (5)

Explore Approved Drugs

1 – 5 of 5

furosemide

SLC12A1Tclin Transporter

INHIBITOR IC50 : 6.2

bumetanide

SLC12A1Tclin Transporter

INHIBITOR Ki : 7.6

ethacrynic acid

SLC12A1Tclin Transporter

INHIBITOR :

piretanide

SLC12A1Tclin Transporter

INHIBITOR Kd : 8.3

torsemide

SLC12A1Tclin Transporter

INHIBITOR IC50 : 6.4

GWAS Traits (7)

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
skin pigmentation measurement	EFO_0007009	3	3	2	3.5	92.1
skin pigmentation	EFO_0003784	2	2	0	8.2	84.6
lymphocyte count	EFO_0004587	2	2	2		71.4
lymphocyte percentage of leukocytes	EFO_0007993	1	1	1		51.7
body height	EFO_0004339	1	1	1		27.2

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
skin pigmentation measurement	EFO_0007009	2	3.5	92.1
skin pigmentation	EFO_0003784	0	8.2	84.6
lymphocyte count	EFO_0004587	2		71.4
lymphocyte percentage of leukocytes	EFO_0007993	1		51.7
body height	EFO_0004339	1		27.2

Reset Zoom  Beta Count   Odds Ratio

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	solute carrier family 12 member 1	VGNC:7779	453410
Macaque	solute carrier family 12 member 1		714289
Mouse	solute carrier family 12, member 1	MGI:103150	20495
Rat	solute carrier family 12 member 1	RGD:3685	25065
Dog	solute carrier family 12 member 1	VGNC:46218	478292

Species	Name	OMA	EggNOG	Inparanoid
Chimp	solute carrier family 12 member 1
Macaque	solute carrier family 12 member 1
Mouse	solute carrier family 12, member 1
Rat	solute carrier family 12 member 1
Dog	solute carrier family 12 member 1

Protein Structure (0 Structures, 1 AlphaFold Model)

tutorial

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-Q13621-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (8)

Reactome (8)

Cation-coupled Chloride cotransporters (R-HSA-426117)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 8

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cation-coupled Chloride cotransporters	7 targets	R-HSA-426117
Reactome	Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1 targets	R-HSA-5619104
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Disorders of transmembrane transporters	178 targets	R-HSA-5619115
Reactome	SLC transporter disorders	100 targets	R-HSA-5619102

Name	Explore in Pharos	Explore in Source
Cation-coupled Chloride cotransporters	7 targets	R-HSA-426117
Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1 targets	R-HSA-5619104
Disease	1105 targets	R-HSA-1643685
Disorders of transmembrane transporters	178 targets	R-HSA-5619115
SLC transporter disorders	100 targets	R-HSA-5619102

Gene Ontology Terms (17)

Functions (4)

Components (5)

Processes (8)

Find Similar Targets

Items per page:

10

1 – 4 of 4

GO Term	Evidence	Assigned by
potassium:chloride symporter activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
sodium ion transmembrane transporter activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
sodium:chloride symporter activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
sodium:potassium:chloride symporter activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Protein-Protein Interactions (84)

Explore Interacting Targets

1 – 10 of 84

• See Interactions on String-DB

STK39

Tchem

Family:  Kinase

Novelty:  0.00548476

Score:  0.939

Data Source:  STRINGDB

KCNJ1

Tchem

Family:  IC

Novelty:  0.0025066

Score:  0.906

Data Source:  STRINGDB

WNK1

Tchem

Family:  Kinase

Novelty:  0.00270535

Score:  0.886

Data Source:  STRINGDB

WNK4

Tbio

Family:  Kinase

Novelty:  0.00795905

Score:  0.856

Data Source:  STRINGDB

CLCNKB

Tchem

Family:  IC

Novelty:  0.00982208

Score:  0.85

Data Source:  STRINGDB

SLC9A3

Tclin

Family:  Transporter

Novelty:  0.00146466

Score:  0.845

Data Source:  STRINGDB

AQP2

Tbio

Novelty:  0.00088471

Score:  0.837

Data Source:  STRINGDB

WNK3

Tchem

Family:  Kinase

Novelty:  0.03382701

Score:  0.835

Data Source:  STRINGDB

SLC4A2

Tbio

Family:  Transporter

Novelty:  0.02448062

Score:  0.806

Data Source:  STRINGDB

BSND

Tbio

Novelty:  0.01638636

Score:  0.8

Data Source:  STRINGDB

Publication Statistics

PubMed Score  319.38

PubMed score by year

Reset Zoom

PubTator Score  304.55

PubTator score by year

Reset Zoom

Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

ProtVista Viewer

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Bartter syndrome
Chloride
Complete proteome
Disease mutation
Glycoprotein
Ion transport
Membrane
Neurodegeneration
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
BMI-adjusted waist circumference
body height
lymphocyte count
lymphocyte percentage of leukocytes
neutrophil percentage of leukocytes
skin pigmentation
skin pigmentation measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
mortality/aging
renal/urinary system phenotype
skeleton phenotype