Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTD62VB)

• DTP Name: Electroneutral potassium-chloride cotransporter 2 (SLC12A5)
• Gene Name: SLC12A5
• UniProt ID: Q9H2X9 (S12A5_HUMAN)
• VARIDT ID: DTD0086
• Synonyms: hKCC2; Neuronal K-Cl cotransporter; K-Cl cotransporter 2; KCC2; KIAA1176; Solute carrier family 12 member 5
• DTP Family: Cation-Chloride Cotransporter (CCC) Family
• Tissue Specificity: Brain specific. Detected in neuronal cells.
• Sequence:
  MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVKGDGNPKESSPFINSTDTEKG
  KEYDGKNMALFEEEMDTSPMVSSLLSGLANYTNLPQGSREHEEAENNEGGKKKPVQAPRM
  GTFMGVYLPCLQNIFGVILFLRLTWVVGIAGIMESFCMVFICCSCTMLTAISMSAIATNG
  VVPAGGSYYMISRSLGPEFGGAVGLCFYLGTTFAGAMYILGTIEILLAYLFPAMAIFKAE
  DASGEAAAMLNNMRVYGTCVLTCMATVVFVGVKYVNKFALVFLGCVILSILAIYAGVIKS
  AFDPPNFPICLLGNRTLSRHGFDVCAKLAWEGNETVTTRLWGLFCSSRFLNATCDEYFTR
  NNVTEIQGIPGAASGLIKENLWSSYLTKGVIVERSGMTSVGLADGTPIDMDHPYVFSDMT
  SYFTLLVGIYFPSVTGIMAGSNRSGDLRDAQKSIPTGTILAIATTSAVYISSVVLFGACI
  EGVVLRDKFGEAVNGNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAISRDG
  IVPFLQVFGHGKANGEPTWALLLTACICEIGILIASLDEVAPILSMFFLMCYMFVNLACA
  VQTLLRTPNWRPRFRYYHWTLSFLGMSLCLALMFICSWYYALVAMLIAGLIYKYIEYRGA
  EKEWGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVLVRVDQDQNVVHPQLLSLTSQ
  LKAGKGLTIVGSVLEGTFLENHPQAQRAEESIRRLMEAEKVKGFCQVVISSNLRDGVSHL
  IQSGGLGGLQHNTVLVGWPRNWRQKEDHQTWRNFIELVRETTAGHLALLVTKNVSMFPGN
  PERFSEGSIDVWWIVHDGGMLMLLPFLLRHHKVWRKCKMRIFTVAQMDDNSIQMKKDLTT
  FLYHLRITAEVEVVEMHESDISAYTYEKTLVMEQRSQILKQMHLTKNEREREIQSITDES
  RGSIRRKNPANTRLRLNVPEETAGDSEEKPEEEVQLIHDQSAPSCPSSSPSPGEEPEGEG
  ETDPEKVHLTWTKDKSVAEKNKGPSPVSSEGIKDFFSMKPEWENLNQSNVRRMHTAVRLN
  EVIVKKSRDAKLVLLNMPGPPRNRNGDENYMEFLEVLTEHLDRVMLVRGGGREVITIYS
• Function: This transporter 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.
• Endogenous Substrate(s): Chloride
• TCDB ID: 2.A.30.1.18
• Gene ID: 57468
• KEGG Pathway: GABAergic synapse (hsa04727)
• Reactome Pathway: Cation-coupled Chloride cotransporters (R-HSA-426117)

Molecular Interaction Atlas (MIA) of This DTP

1 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[3]

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	5.17E-02	-2.84E-03	-1.25E-02
Adrenocortical carcinoma	2D11.Z	Kidney	1.26E-04	2.57E-01	6.56E-01
Alopecia	ED70	Skin from scalp	1.31E-02	7.80E-02	3.93E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.97E-03	-2.07E-01	-3.35E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	5.69E-01	-1.00E-01	-3.63E-01
Aortic stenosis	BB70	Calcified aortic valve	8.87E-01	4.68E-02	4.39E-02
Apnea	7A40	Hyperplastic tonsil	2.84E-01	-5.96E-01	-1.08E+00
Arthropathy	FA00-FA5Z	Peripheral blood	4.86E-01	2.12E-02	1.15E-01
Asthma	CA23	Nasal and bronchial airway	1.98E-01	-3.22E-02	-1.36E-01
Atopic dermatitis	EA80	Skin	1.58E-01	-7.74E-02	-4.31E-01
Autism	6A02	Whole blood	1.00E-01	-1.23E-01	-4.60E-01
Autoimmune uveitis	9A96	Peripheral monocyte	4.49E-02	-2.07E-01	-1.46E+00
Autosomal dominant monocytopenia	4B04	Whole blood	2.32E-01	3.12E-02	2.22E-01
Bacterial infection of gingival	1C1H	Gingival tissue	5.10E-03	5.81E-02	1.70E-01
Batten disease	5C56.1	Whole blood	8.42E-01	8.94E-04	5.97E-03
Behcet's disease	4A62	Peripheral blood	8.95E-01	8.61E-02	2.80E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	4.21E-01	1.82E-02	1.03E-01
Bladder cancer	2C94	Bladder tissue	7.09E-05	9.95E-01	2.87E+00
Breast cancer	2C60-2C6Z	Breast tissue	6.48E-07	-1.21E-01	-2.96E-01
Cardioembolic stroke	8B11.20	Whole blood	9.80E-01	7.93E-03	3.46E-02
Cervical cancer	2C77	Cervical tissue	8.43E-02	1.23E-01	3.13E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.51E-01	6.23E-02	2.84E-01
Chronic hepatitis C	1E51.1	Whole blood	9.81E-01	1.03E-01	4.75E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	7.48E-02	1.25E-01	5.25E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	6.01E-01	1.21E-03	6.46E-03
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.11E-02	2.67E-01	7.68E-01
Colon cancer	2B90	Colon tissue	1.45E-01	2.19E-02	7.62E-02
Coronary artery disease	BA80-BA8Z	Peripheral blood	2.41E-01	-2.68E-01	-5.18E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	5.04E-01	-5.75E-02	-3.02E-01
Endometriosis	GA10	Endometrium tissue	7.21E-02	1.20E-01	3.99E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	9.39E-01	-3.51E-03	-2.00E-02
Familial hypercholesterolemia	5C80.00	Whole blood	4.74E-01	8.83E-02	3.29E-01
Gastric cancer	2B72	Gastric tissue	6.72E-01	3.27E-02	1.06E-01
Glioblastopma	2A00.00	Nervous tissue	1.11E-216	-4.94E+00	-3.41E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	4.67E-01	-1.01E-01	-3.37E-01
Head and neck cancer	2D42	Head and neck tissue	2.85E-02	8.65E-02	3.15E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	2.59E-01	-7.81E-01	-6.23E-01
Huntington's disease	8A01.10	Whole blood	3.62E-01	8.79E-02	4.96E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	9.82E-01	1.17E-01	3.69E-01
Immunodeficiency	4A00-4A20	Peripheral blood	2.40E-03	1.34E-01	1.35E+00
Influenza	1.00E+30	Whole blood	1.00E-02	6.06E-01	4.14E+00
Interstitial cystitis	GC00.3	Bladder tissue	7.06E-01	1.59E-02	1.16E-01
Intracranial aneurysm	8B01.0	Intracranial artery	2.41E-01	4.91E-02	3.08E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	5.99E-01	-1.22E-03	-3.21E-03
Ischemic stroke	8B11	Peripheral blood	1.03E-03	1.17E-01	8.48E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	7.50E-01	-2.29E-02	-8.54E-02
Lateral sclerosis	8B60.4	Cervical spinal cord	6.03E-01	-4.19E-02	-3.49E-02
Lateral sclerosis	8B60.4	Skin	5.28E-01	3.37E-02	1.80E-01
Liver cancer	2C12.0	Liver tissue	4.90E-02	-9.14E-02	-3.93E-01
Liver failure	DB99.7-DB99.8	Liver tissue	1.43E-01	2.16E-01	7.53E-01
Lung cancer	2C25	Lung tissue	8.33E-01	-3.68E-02	-1.31E-01
Lupus erythematosus	4A40	Whole blood	8.52E-01	-2.62E-02	-8.28E-02
Major depressive disorder	6A70-6A7Z	Whole blood	1.89E-01	-4.94E-02	-1.61E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.03E-02	7.82E-02	4.80E-01
Melanoma	2C30	Skin	2.81E-01	5.58E-01	6.87E-01
Multiple myeloma	2A83.1	Bone marrow	5.43E-03	-8.90E-01	-1.44E+00
Multiple myeloma	2A83.1	Peripheral blood	2.87E-01	1.45E-01	4.35E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.94E-01	-7.21E-02	-3.72E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	7.84E-01	-1.23E-03	-6.80E-03
Myelofibrosis	2A20.2	Whole blood	8.20E-02	6.38E-02	3.72E-01
Myocardial infarction	BA41-BA50	Peripheral blood	1.86E-02	2.94E-01	6.09E-01
Myopathy	8C70.6	Muscle tissue	2.79E-01	-7.12E-02	-3.68E-01
Neonatal sepsis	KA60	Whole blood	2.09E-02	9.68E-02	3.50E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	2.13E-09	-3.73E+00	-5.23E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	9.56E-01	2.94E-02	1.70E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.39E-03	1.47E-01	4.78E+00
Olive pollen allergy	CA08.00	Peripheral blood	3.46E-01	1.07E-01	5.60E-01
Oral cancer	2B6E	Oral tissue	2.29E-01	-2.56E-01	-4.61E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	7.28E-01	-1.03E-01	-3.97E-01
Osteoporosis	FB83.1	Bone marrow	9.09E-01	-3.42E-02	-8.50E-01
Ovarian cancer	2C73	Ovarian tissue	3.03E-03	1.26E-01	6.63E-01
Pancreatic cancer	2C10	Pancreas	1.09E-01	-2.36E-01	-4.97E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	5.68E-01	-4.43E-02	-4.10E-02
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	7.81E-01	-1.50E-03	-1.15E-02
Pituitary cancer	2D12	Pituitary tissue	3.85E-05	1.28E+00	2.46E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	9.65E-09	2.15E+00	5.82E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	8.42E-01	-7.22E-02	-3.06E-01
Polycythemia vera	2A20.4	Whole blood	5.40E-03	2.35E-02	1.71E-01
Pompe disease	5C51.3	Biceps muscle	3.55E-02	-8.78E-02	-5.51E-01
Preterm birth	KA21.4Z	Myometrium	6.96E-01	3.97E-02	1.55E-01
Prostate cancer	2C82	Prostate	4.52E-02	-5.06E-01	-8.33E-01
Psoriasis	EA90	Skin	3.59E-07	-2.67E-01	-6.74E-01
Rectal cancer	2B92	Rectal colon tissue	9.91E-01	-4.78E-03	-1.21E-02
Renal cancer	2C90-2C91	Kidney	1.67E-02	-4.50E-01	-1.44E+00
Retinoblastoma	2D02.2	Uvea	1.64E-08	-7.61E+00	-3.53E+01
Rheumatoid arthritis	FA20	Synovial tissue	1.78E-03	-3.16E-01	-1.64E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	5.38E-01	-4.33E-02	-2.76E-01
Schizophrenia	6A20	Prefrontal cortex	1.15E-01	-1.13E-02	-3.80E-03
Schizophrenia	6A20	Superior temporal cortex	4.49E-01	-1.27E-01	-1.83E-01
Scleroderma	4A42.Z	Whole blood	2.97E-01	-1.15E-01	-6.76E-01
Seizure	8A60-8A6Z	Whole blood	3.32E-01	-1.89E-02	-1.35E-01
Sensitive skin	EK0Z	Skin	2.59E-01	1.15E-01	7.73E-01
Sepsis with septic shock	1G41	Whole blood	1.43E-07	1.36E-01	4.39E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	7.89E-02	3.01E-01	7.17E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	3.51E-01	2.57E-01	1.21E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	6.49E-01	4.28E-02	7.02E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	2.94E-01	3.27E-02	1.03E+00
Skin cancer	2C30-2C3Z	Skin	1.90E-02	-1.24E-01	-2.67E-01
Thrombocythemia	3B63	Whole blood	4.94E-01	-5.33E-02	-3.12E-01
Thrombocytopenia	3B64	Whole blood	9.57E-01	0.00E+00	0.00E+00
Thyroid cancer	2D10	Thyroid	1.55E-04	1.15E-01	4.39E-01
Tibial muscular dystrophy	8C75	Muscle tissue	5.33E-02	8.11E-02	4.42E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	1.02E-01	-5.07E-01	-7.99E+00
Type 2 diabetes	5A11	Liver tissue	8.46E-01	1.69E-01	2.26E-01
Ureter cancer	2C92	Urothelium	7.72E-01	-2.28E-02	-8.15E-02
Uterine cancer	2C78	Endometrium tissue	3.17E-12	3.99E-01	9.34E-01
Vitiligo	ED63.0	Skin	7.41E-01	-8.36E-02	-3.72E-01

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Solute carrier family 12 member 5 (SLC12A5) DTT Info
• DTP DTT Type: Literature-reported

3 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CLP-635	DM1B0PY	Epilepsy	8A60-8A68	Investigative	[1]
DIOA	DMBKJL8	Discovery agent	N.A.	Investigative	[1]
VU0240551	DMU3YRH	Discovery agent	N.A.	Investigative	[2]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 972).
• [2] Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5383-8.
• [3] Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci. 2010 Oct;45(2):173-9.