Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT2WLAD)

• DTP Name: Urate anion exchanger 1 (SLC22A12)
• Gene Name: SLC22A12
• UniProt ID: Q96S37 (S22AC_HUMAN)
• VARIDT ID: DTD0027
• Synonyms: OAT4L; OATL4; Organic anion transporter 4-like protein; RST; Renal-specific transporter; SLC22A12; Solute carrier family 22 member 12; URAT1
• DTP Family:
  Major Facilitator Superfamily (MFS)
  Organic Cation Transporter (OCT) Family
• Tissue Specificity: Detected in kidney (at protein level).Detected in fetal and adult kidney. Detected in epithelial cellsof proximal tubules in renal cortex.
• Sequence:
  MAFSELLDLVGGLGRFQVLQTMALMVSIMWLCTQSMLENFSAAVPSHRCWAPLLDNSTAQ
  ASILGSLSPEALLAISIPPGPNQRPHQCRRFRQPQWQLLDPNATATSWSEADTEPCVDGW
  VYDRSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDRFGRRLVLTWSY
  LQMAVMGTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLLMEWTAARARPLVMTLNSLG
  FSFGHGLTAAVAYGVRDWTLLQLVVSVPFFLCFLYSWWLAESARWLLTTGRLDWGLQELW
  RVAAINGKGAVQDTLTPEVLLSAMREELSMGQPPASLGTLLRMPGLRFRTCISTLCWFAF
  GFTFFGLALDLQALGSNIFLLQMFIGVVDIPAKMGALLLLSHLGRRPTLAASLLLAGLCI
  LANTLVPHEMGALRSALAVLGLGGVGAAFTCITIYSSELFPTVLRMTAVGLGQMAARGGA
  ILGPLVRLLGVHGPWLPLLVYGTVPVLSGLAALLLPETQSLPLPDTIQDVQNQAVKKATH
  GTLGNSVLKSTQF
• Function: This transporter regulates blood urate levels via controlling saturable urate uptake by facilitating the exchange of urate against organic anions in kediney.
• Endogenous Substrate(s): Anions
• TCDB ID: 2.A.1.19.11
• Gene ID: 116085
• Reactome Pathway:
  Defective SLC22A12 causes renal hypouricemia 1 (RHUC1) (R-HSA-5619071)
  Organic anion transport (R-HSA-561048)

Molecular Interaction Atlas (MIA) of This DTP

1 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Oxypurinol	DMURH4X	Heart failure	BD10-BD13	Phase 2/3	[8]

2 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Orotate	DMMB29S	Discovery agent	N.A.	Investigative	[9]
uric acid	DMA1MKT	Discovery agent	N.A.	Investigative	[10]

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	1.21E-01	2.51E-02	8.85E-02
Adrenocortical carcinoma	2D11.Z	Kidney	4.97E-01	3.91E-02	7.98E-02
Alopecia	ED70	Skin from scalp	4.82E-01	1.34E-02	7.08E-02
Alzheimer's disease	8A20	Entorhinal cortex	4.41E-01	-9.18E-03	-4.07E-02
Ankylosing spondylitis	FA92.0	Pheripheral blood	1.28E-01	-2.93E-02	-4.11E-01
Aortic stenosis	BB70	Calcified aortic valve	6.28E-01	4.33E-02	6.34E-02
Apnea	7A40	Hyperplastic tonsil	5.07E-02	-7.47E-01	-1.42E+00
Arthropathy	FA00-FA5Z	Peripheral blood	5.25E-01	-4.72E-04	-2.31E-03
Asthma	CA23	Nasal and bronchial airway	8.64E-01	-1.72E-01	-3.16E-01
Atopic dermatitis	EA80	Skin	1.80E-03	-9.73E-02	-7.20E-01
Autism	6A02	Whole blood	7.73E-01	-5.65E-02	-1.87E-01
Autoimmune uveitis	9A96	Peripheral monocyte	9.47E-03	-2.46E-01	-1.19E+00
Autosomal dominant monocytopenia	4B04	Whole blood	5.89E-01	4.32E-02	2.02E-01
Bacterial infection of gingival	1C1H	Gingival tissue	1.04E-01	1.35E-01	3.49E-01
Batten disease	5C56.1	Whole blood	7.60E-01	8.28E-02	7.87E-01
Behcet's disease	4A62	Peripheral blood	4.70E-01	4.63E-04	2.01E-03
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	6.67E-01	-6.00E-03	-2.16E-02
Bladder cancer	2C94	Bladder tissue	6.97E-04	6.39E-01	2.31E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.62E-10	-1.20E-01	-3.30E-01
Cardioembolic stroke	8B11.20	Whole blood	4.74E-02	1.49E-01	7.14E-01
Cervical cancer	2C77	Cervical tissue	2.18E-01	1.93E-01	4.90E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	7.34E-01	-8.18E-03	-2.53E-02
Chronic hepatitis C	1E51.1	Whole blood	6.89E-01	5.88E-02	3.52E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	1.03E-01	2.27E-01	6.61E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	3.21E-02	1.15E-01	4.02E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	6.60E-02	1.76E-01	5.31E-01
Colon cancer	2B90	Colon tissue	6.63E-09	-2.22E-01	-5.51E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	6.36E-01	-1.91E-01	-3.89E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	5.44E-01	-6.16E-02	-3.19E-01
Endometriosis	GA10	Endometrium tissue	1.48E-01	1.77E-01	6.20E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	8.80E-01	-3.94E-02	-1.84E-01
Familial hypercholesterolemia	5C80.00	Whole blood	4.97E-01	1.48E-01	5.00E-01
Gastric cancer	2B72	Gastric tissue	7.40E-01	-3.08E-02	-2.31E-01
Glioblastopma	2A00.00	Nervous tissue	6.83E-22	-2.63E-01	-6.17E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	3.47E-04	-4.07E-01	-1.40E+00
Head and neck cancer	2D42	Head and neck tissue	8.24E-03	-9.09E-02	-3.23E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	1.85E-01	-3.00E-01	-7.08E-01
Huntington's disease	8A01.10	Whole blood	4.80E-01	4.04E-02	2.03E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	5.96E-01	1.22E-01	3.05E-01
Immunodeficiency	4A00-4A20	Peripheral blood	6.78E-01	-7.94E-02	-4.39E-01
Influenza	1.00E+30	Whole blood	4.74E-02	5.82E-01	3.92E+00
Interstitial cystitis	GC00.3	Bladder tissue	7.72E-01	1.06E-02	6.28E-02
Intracranial aneurysm	8B01.0	Intracranial artery	6.56E-01	-7.89E-02	-5.17E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	4.24E-01	-1.28E-02	-5.35E-02
Ischemic stroke	8B11	Peripheral blood	4.49E-01	0.00E+00	0.00E+00
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.07E-01	1.27E-01	4.27E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	1.85E-01	3.67E-01	8.46E-01
Lateral sclerosis	8B60.4	Skin	6.61E-01	4.62E-02	1.55E-01
Liver cancer	2C12.0	Liver tissue	8.49E-01	-4.02E-02	-1.25E-01
Liver failure	DB99.7-DB99.8	Liver tissue	7.63E-02	2.40E-01	5.58E-01
Lung cancer	2C25	Lung tissue	9.71E-02	2.91E-02	1.03E-01
Lupus erythematosus	4A40	Whole blood	3.23E-02	-8.93E-02	-1.15E-01
Major depressive disorder	6A70-6A7Z	Whole blood	6.72E-01	7.13E-02	2.70E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.02E-01	-1.56E-02	-5.35E-02
Melanoma	2C30	Skin	6.71E-01	1.01E-01	1.23E-01
Multiple myeloma	2A83.1	Bone marrow	1.04E-02	-5.22E-01	-1.36E+00
Multiple myeloma	2A83.1	Peripheral blood	9.70E-01	-4.05E-02	-1.73E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	4.40E-01	-6.93E-03	-3.05E-02
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	6.90E-01	3.98E-02	1.28E-01
Myelofibrosis	2A20.2	Whole blood	5.89E-03	1.98E-01	1.36E+00
Myocardial infarction	BA41-BA50	Peripheral blood	2.91E-01	1.70E-01	2.45E-01
Myopathy	8C70.6	Muscle tissue	4.94E-02	-5.37E-01	-1.25E+00
Neonatal sepsis	KA60	Whole blood	2.39E-04	1.55E-01	4.41E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	3.58E-05	-7.55E-01	-2.51E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	8.34E-01	-4.96E-02	-2.12E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	8.48E-01	-5.60E-02	-1.98E-01
Olive pollen allergy	CA08.00	Peripheral blood	9.13E-02	3.13E-01	1.46E+00
Oral cancer	2B6E	Oral tissue	4.61E-07	-4.27E-01	-1.15E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	4.63E-01	-1.63E-01	-6.50E-01
Osteoporosis	FB83.1	Bone marrow	4.22E-01	3.20E-01	2.12E+00
Ovarian cancer	2C73	Ovarian tissue	1.56E-01	-6.75E-02	-1.78E-01
Pancreatic cancer	2C10	Pancreas	3.58E-01	-5.69E-02	-1.11E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	6.74E-01	4.19E-02	1.10E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	6.05E-03	-1.74E-01	-9.72E-01
Pituitary cancer	2D12	Pituitary tissue	8.63E-01	2.12E-02	4.33E-02
Pituitary gonadotrope tumour	2D12	Pituitary tissue	9.12E-01	-9.11E-04	-1.50E-03
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	9.50E-03	-1.76E-01	-9.19E-01
Polycythemia vera	2A20.4	Whole blood	1.39E-06	1.45E-01	8.73E-01
Pompe disease	5C51.3	Biceps muscle	1.07E-01	-5.64E-02	-3.33E-01
Preterm birth	KA21.4Z	Myometrium	5.15E-01	6.68E-03	5.54E-02
Prostate cancer	2C82	Prostate	1.41E-04	-1.43E+00	-1.52E+00
Psoriasis	EA90	Skin	3.65E-08	-9.50E-02	-2.20E-01
Rectal cancer	2B92	Rectal colon tissue	6.77E-01	-6.27E-02	-2.27E-01
Renal cancer	2C90-2C91	Kidney	2.43E-03	-3.37E+00	-1.91E+00
Retinoblastoma	2D02.2	Uvea	2.86E-05	-7.04E-01	-4.12E+00
Rheumatoid arthritis	FA20	Synovial tissue	3.99E-03	-6.83E-01	-1.85E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	6.72E-01	2.69E-02	1.48E-01
Schizophrenia	6A20	Prefrontal cortex	2.65E-01	6.57E-02	1.67E-01
Schizophrenia	6A20	Superior temporal cortex	8.21E-01	4.55E-02	2.08E-01
Scleroderma	4A42.Z	Whole blood	1.96E-03	-3.71E-01	-1.73E+00
Seizure	8A60-8A6Z	Whole blood	6.06E-01	-3.58E-03	-1.71E-02
Sensitive skin	EK0Z	Skin	6.33E-01	-3.78E-02	-1.55E-01
Sepsis with septic shock	1G41	Whole blood	8.45E-10	2.46E-01	7.46E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	4.32E-01	1.91E-01	5.86E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	4.23E-01	2.42E-02	5.51E-02
Simpson golabi behmel syndrome	LD2C	Adipose tissue	6.48E-01	1.43E-01	5.10E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	6.92E-01	1.21E-01	3.58E-01
Skin cancer	2C30-2C3Z	Skin	3.48E-07	-1.48E-01	-2.48E-01
Thrombocythemia	3B63	Whole blood	6.72E-02	1.61E-01	1.08E+00
Thrombocytopenia	3B64	Whole blood	2.85E-01	-3.50E-01	-1.46E+00
Thyroid cancer	2D10	Thyroid	7.09E-02	5.20E-02	2.07E-01
Tibial muscular dystrophy	8C75	Muscle tissue	5.58E-03	-3.43E-01	-1.19E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	8.74E-01	3.67E-02	2.01E-01
Type 2 diabetes	5A11	Liver tissue	4.36E-02	-2.36E-01	-2.68E+00
Ureter cancer	2C92	Urothelium	5.60E-01	6.27E-02	1.64E-01
Uterine cancer	2C78	Endometrium tissue	2.54E-14	3.22E-01	8.47E-01
Vitiligo	ED63.0	Skin	8.11E-01	-9.89E-02	-5.69E-01

Drug Affinity of This DTP Assessed by Cell Line

Clinical Trial Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Oxypurinol	Phase 2/3	Oocytes-URAT1	Km = 794.0 microM	[8]

Investigative Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
uric acid	Investigative	Oocytes-URAT1	Km = 357.6 microM	[10]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Urate anion exchanger 1 (URAT1) DTT Info
• DTP DTT Type: Successful

1 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lesinurad	DMUR64T	Hyperuricaemia	5C55.Y	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dotinurad	DM0UPQJ	Gout	FA25	Phase 3	[2]
AR882	DMFGYZ8	Gout	FA25	Phase 2	[3]
RDEA-684	DMNWYHD	Gout	FA25	Phase 2	[1]
RDEA3170	DM1TKG4	Hyperuricaemia	5C55.Y	Phase 2	[4]
URC102	DMY89BN	Gout	FA25	Phase 2	[5]

18 Patented Agent(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-ethyl-3-(4-hydroxy) benzoyl benzofuran derivative 1	DMHYIAV	N. A.	N. A.	Patented	[6]
3-benzyloxyphenyloxoacetic acid derivative 1	DMB6M3Y	N. A.	N. A.	Patented	[6]
Benzene sulfonamide derivative 16	DMATBZW	N. A.	N. A.	Patented	[6]
Benzofurans derivative 1	DM4198Z	N. A.	N. A.	Patented	[6]
Benzoic acid derivative 1	DM5ZKR2	N. A.	N. A.	Patented	[6]
Cycloalkyl acid derivative 1	DMXMGSP	N. A.	N. A.	Patented	[6]
Cycloalkyl acid derivative 2	DM09LY3	N. A.	N. A.	Patented	[6]
Fused heterocyclic compound 12	DMSYD6Z	N. A.	N. A.	Patented	[6]
Phenylthioacetate derivative 1	DMTHXUC	N. A.	N. A.	Patented	[6]
PMID27414413-Compound-Figure6right	DMUG9X0	N. A.	N. A.	Patented	[6]
PMID27414413-Compound-Figure8right	DMTZNSM	N. A.	N. A.	Patented	[6]
Ring-fused compound 1	DMUB7RV	N. A.	N. A.	Patented	[6]
Succinamide derivative 1	DMTXDSG	N. A.	N. A.	Patented	[6]
Sulfonamide derivative 10	DMA32GJ	N. A.	N. A.	Patented	[6]
Sulfonamide derivative 11	DMJBR86	N. A.	N. A.	Patented	[6]
Tetrazole acetic acid derivative 1	DM52683	N. A.	N. A.	Patented	[6]
Tihoacetate derivative 1	DM6QHO0	N. A.	N. A.	Patented	[6]
Triazole propanedioic acid derivative 1	DM8LFGS	N. A.	N. A.	Patented	[6]

1 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MORIN	DM2OGZ5	Discovery agent	N.A.	Investigative	[7]

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: 1031).
• [2] Dotinurad: a novel selective urate reabsorption inhibitor for the treatment of hyperuricemia and gout. Expert Opin Pharmacother. 2021 Aug;22(11):1397-1406.
• [3] Clinical pipeline report, company report or official report of Arthrosi Therapeutics
• [4] The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013; 14: 164.
• [5] Clinical pipeline report, company report or official report of Chugai Pharmaceutical (2013).
• [6] Urate transporter URAT1 inhibitors: a patent review (2012 - 2015).Expert Opin Ther Pat. 2016 Jul 30:1-10.
• [7] Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) express... Drug Metab Dispos. 2007 Jun;35(6):981-6.
• [8] Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos. 2005 Dec;33(12):1791-5.
• [9] Human urate transporter 1 (hURAT1) mediates the transport of orotate. J Physiol Sci. 2011 May;61(3):253-7.
• [10] Concentration-dependent mode of interaction of angiotensin II receptor blockers with uric acid transporter. J Pharmacol Exp Ther. 2007 Jan;320(1):211-7.