SLC22A7

Summary

SLC22A7 (solute carrier family 22 member 7, HGNC:10971) is a protein-coding gene on chromosome 6p21.1, encoding Solute carrier family 22 member 7 (Q9Y694). Functions as a Na(+)-independent bidirectional multispecific transporter.

The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 10864 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 64 total
• Druggable target: yes
• MANE Select transcript: NM_153320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10971
Approved symbol	SLC22A7
Name	solute carrier family 22 member 7
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	NLT, OAT2
Ensembl gene	ENSG00000137204
Ensembl biotype	protein_coding
OMIM	604995
Entrez	10864

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000372574, ENST00000372585, ENST00000372589, ENST00000436107, ENST00000449231, ENST00000451757, ENST00000480882, ENST00000487175, ENST00000498232, ENST00000875170, ENST00000875171, ENST00000875172, ENST00000875173, ENST00000875174, ENST00000875175, ENST00000875176, ENST00000875177, ENST00000875178, ENST00000875179, ENST00000875180, ENST00000875181, ENST00000875182

RefSeq mRNA: 2 — MANE Select: NM_153320 NM_006672, NM_153320

CCDS: CCDS4892, CCDS4893

Canonical transcript exons

ENST00000372585 — 11 exons

Exon	Start	End
ENSE00002151404	43304671	43305538
ENSE00002153800	43304038	43304244
ENSE00002184598	43302200	43302414
ENSE00002184962	43302655	43302763
ENSE00003479987	43299092	43299097
ENSE00003537429	43299390	43299493
ENSE00003549679	43301583	43301692
ENSE00003620543	43301135	43301258
ENSE00003788915	43299627	43299781
ENSE00003789523	43299898	43300066
ENSE00003902676	43298260	43298751

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 98.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0803 / max 623.4606, expressed in 40 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67896	0.4546	31
67895	0.2500	23
67897	0.2472	29
67894	0.1143	15
67893	0.0142	3

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.63	gold quality
liver	UBERON:0002107	97.33	gold quality
adult mammalian kidney	UBERON:0000082	89.28	gold quality
nephron tubule	UBERON:0001231	86.17	gold quality
kidney epithelium	UBERON:0004819	84.62	gold quality
tongue squamous epithelium	UBERON:0006919	83.75	gold quality
diaphragm	UBERON:0001103	83.51	silver quality
kidney	UBERON:0002113	83.49	gold quality
renal medulla	UBERON:0000362	83.02	gold quality
adult organism	UBERON:0007023	82.95	gold quality
vena cava	UBERON:0004087	81.62	silver quality
type B pancreatic cell	CL:0000169	80.79	silver quality
olfactory bulb	UBERON:0002264	79.96	silver quality
triceps brachii	UBERON:0001509	78.23	gold quality
renal glomerulus	UBERON:0000074	77.88	gold quality
metanephric glomerulus	UBERON:0004736	77.66	gold quality
right testis	UBERON:0004534	77.63	gold quality
gluteal muscle	UBERON:0002000	77.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.52	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.34	gold quality
left testis	UBERON:0004533	76.88	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.65	silver quality
cervix squamous epithelium	UBERON:0006922	75.45	gold quality
tendon of biceps brachii	UBERON:0008188	75.23	gold quality
testis	UBERON:0000473	74.32	gold quality
body of tongue	UBERON:0011876	74.10	silver quality
cortex of kidney	UBERON:0001225	73.87	gold quality
mucosa of urinary bladder	UBERON:0001259	73.59	gold quality
hair follicle	UBERON:0002073	73.56	gold quality
cervix epithelium	UBERON:0004801	73.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, NR0B2, NR1H4

miRNA regulators (miRDB)

35 targeting SLC22A7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-581	98.39	67.42	835
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302

Literature-anchored findings (GeneRIF, showing 19)

• elucidation of the molecular mechanism for renal tetracycline transport by human organic anion transporters (hOATs) using proximal tubular cells stably expressing hOATs (PMID:11855680)
• hOAT2 is a highly efficient, facilitative transporter of cGMP and may be involved in cGMP signaling in many tissues. (PMID:18216183)
• results suggest that genetic polymorphisms may not be a significant contributing factor to variations in the hOAT2 expression or hOAT2 transport activity (PMID:19854166)
• Expression of rat OAT2 in HEK (human embryonic kidney)-293 cells stimulates accumulation of zwitterion trigonelline; subsequently, orotic acid is identified as an excellent and specific substrate of OAT2 from human. (PMID:21446918)
• Transport of the antivirals into human embryonic kidney cells was stimulated 10- to 20-fold by expression of OAT2. (PMID:22190696)
• Benzoic acid and specific 2-oxo acids activate hepatic efflux of glutamate at OAT2 (PMID:22981274)
• mitochondrial pathways may affect SLC 22A7 function to promote the occurrence of hepatocellular carcinoma (PMID:23543312)
• At physiologic creatinine concentrations, specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely creatinine transporter, challenging the view that creatinine is solely transported by a cationic pathway (PMID:24646860)
• the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine (PMID:25904762)
• Two novel variants in SLC22A17 and SLC22A7 were significantly associated with anthracycline-induced cardiotoxicity. (PMID:26230641)
• suggest that OAT2-mediated cGMP uptake does not occur via exchange with monocarboxylates, dicarboxylates, and hydroxyl ions (PMID:26377792)
• SLC22A7 variants were not significantly associated with hyperuricemia and gout in a New Zealand Maori and Pacific cohort. (PMID:28371506)
• two human organic anion transporters OAT2 and OAT7 activities were assessed. (PMID:28945155)
• The established OAT2 (SLC22A7)-substrate indomethacin showed a competitive interaction with cyclic nucleotide uptake. (PMID:29244191)
• Lrh-1 transcriptionally regulates Oat2. (PMID:29669824)
• Large interindividual variability was noted in the hepatic expression of OAT2 (16-fold in human liver tissue and 23-fold in hepatocytes). OAT7, on the other hand, showed less interindividual variability (4-fold) in the livers, but high variability for the hepatocyte lots (27-fold). A significant positive correlation in OAT2 and OAT7 expression was observed, but expression levels were neither associated with age nor sex. (PMID:29906129)
• The role of OAT2-mediated hepatic uptake in determining the pharmacokinetics of several clinically important ECCS 1A drugs. (PMID:30135178)
• Nicotinic acid transport into human liver involves organic anion transporter 2 (SLC22A7). (PMID:32001236)
• Plasma microRNA profiles: identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer. (PMID:32081926)

Cross-species orthologs

46 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a7b.1	ENSDARG00000056643
danio_rerio	zmp:0000001102	ENSDARG00000056652
danio_rerio	slc22a7b.3	ENSDARG00000062182
danio_rerio	slc22a7b.2	ENSDARG00000091252
mus_musculus	Slc22a7	ENSMUSG00000067144
rattus_norvegicus	Slc22a7	ENSRNOG00000018420
drosophila_melanogaster	Orct	FBGN0019952
drosophila_melanogaster	CG15221	FBGN0030331
drosophila_melanogaster	Balat	FBGN0033778
drosophila_melanogaster	CG5592	FBGN0035645
drosophila_melanogaster	CG10486	FBGN0035647
drosophila_melanogaster	CG14691	FBGN0037829
drosophila_melanogaster	CG14855	FBGN0038260
drosophila_melanogaster	CG14856	FBGN0038261
drosophila_melanogaster	CG14857	FBGN0038262
drosophila_melanogaster	CG12783	FBGN0038448
drosophila_melanogaster	CG7333	FBGN0038715
drosophila_melanogaster	CG7342	FBGN0038716
drosophila_melanogaster	CG17751	FBGN0038717
drosophila_melanogaster	CG17752	FBGN0038718
drosophila_melanogaster	CG16727	FBGN0038719
drosophila_melanogaster	CG6231	FBGN0038720
drosophila_melanogaster	CG4465	FBGN0038750
drosophila_melanogaster	CG4462	FBGN0038752
drosophila_melanogaster	CG4459	FBGN0038753
drosophila_melanogaster	CG6356	FBGN0039178
drosophila_melanogaster	CG3690	FBGN0040350
drosophila_melanogaster	CG31103	FBGN0051103
drosophila_melanogaster	CG31106	FBGN0051106
drosophila_melanogaster	CG31272	FBGN0051272
drosophila_melanogaster	CG33233	FBGN0053233
drosophila_melanogaster	CG33234	FBGN0053234
drosophila_melanogaster	Orct2	FBGN0086365
drosophila_melanogaster	CG42269	FBGN0259164
drosophila_melanogaster	CG44098	FBGN0264907
caenorhabditis_elegans		WBGENE00003837
caenorhabditis_elegans	oct-1	WBGENE00003842
caenorhabditis_elegans		WBGENE00003843
caenorhabditis_elegans		WBGENE00006220
caenorhabditis_elegans		WBGENE00008110
caenorhabditis_elegans		WBGENE00011456
caenorhabditis_elegans		WBGENE00014127
caenorhabditis_elegans		WBGENE00017751
caenorhabditis_elegans		WBGENE00019408
caenorhabditis_elegans		WBGENE00020701
caenorhabditis_elegans		WBGENE00044455

Paralogs (22): SLC22A16 (ENSG00000004809), SLC22A17 (ENSG00000092096), SLC22A2 (ENSG00000112499), SLC22A23 (ENSG00000137266), SLC22A14 (ENSG00000144671), SLC22A3 (ENSG00000146477), SLC22A8 (ENSG00000149452), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A11 (ENSG00000168065), SLC22A13 (ENSG00000172940), SLC22A1 (ENSG00000175003), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A5 (ENSG00000197375), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Solute carrier family 22 member 7 — Q9Y694 (reviewed: Q9Y694)

Alternative names: Novel liver transporter, Organic anion transporter 2

All UniProt accessions (4): Q9Y694, Q5T047, Q5T051, X6RDF7

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a Na(+)-independent bidirectional multispecific transporter. Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively. Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2’deoxyguanosine and GMP being the preferred substrates. Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways. Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood. Involved in renal secretion and possible reabsorption of creatinine. Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion. Also transports alpha-ketoglutarate and urate. Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified. Non functional transporter. Involved in the uptake of prostaglandin F2-alpha (PGF2-alpha).

Subcellular location. Basolateral cell membrane. Apical cell membrane. Cell membrane Cytoplasm. Cytosol.

Tissue specificity. Mainly expressed in liver and kidney. In kidney, expressed in proximal tubular cells. Also expressed in pancreas, small intestine, spinal cord, lung, brain and heart. Expressed in fetal liver.

Miscellaneous. Involved in the uptake of clinically used drugs such as penciclovir and aciclovir, and contributes to renal and hepatic drug elimination.

Similarity. Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y694-1	1, OAT2-548aa, OAT2-546aa OAT2-tv2	yes
Q9Y694-2	2, OAT2-546aa, OAT2-tv1
Q9Y694-3	3, OAT2-tv3
Q9Y694-4	4

RefSeq proteins (2): NP_006663, NP_696961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004749	Orgcat_transp/SVOP	Family
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF07690

Catalyzed reactions (Rhea), 12 shown:

• prostaglandin E2(out) = prostaglandin E2(in) (RHEA:50984)
• prostaglandin F2alpha(out) = prostaglandin F2alpha(in) (RHEA:50988)
• urate(out) = urate(in) (RHEA:60368)
• estrone 3-sulfate(out) = estrone 3-sulfate(in) (RHEA:71835)
• orotate(out) + L-glutamate(in) = orotate(in) + L-glutamate(out) (RHEA:72043)
• creatinine(in) = creatinine(out) (RHEA:74539)
• guanosine(in) = guanosine(out) (RHEA:75371)
• GTP(in) = GTP(out) (RHEA:75787)
• 3’,5’-cyclic GMP(in) = 3’,5’-cyclic GMP(out) (RHEA:76207)
• GMP(in) = GMP(out) (RHEA:76211)
• 2’-deoxyguanosine(in) = 2’-deoxyguanosine(out) (RHEA:76215)
• GDP(in) = GDP(out) (RHEA:76219)

UniProt features (26 total): transmembrane region 12, splice variant 4, sequence variant 3, sequence conflict 2, chain 1, region of interest 1, glycosylation site 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y694-F1	84.93	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 441 (important for glutamate counteranion efflux)

Glycosylation sites (1): 91

Mutagenesis-validated functional residues (1):

Position	Phenotype
441	loss of glutamate transport activity; strong decrease in orotate transport activity.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-561048	Organic anion transport by SLC22 transporters
R-HSA-9749641	Aspirin ADME
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-549132
R-HSA-9748784	Drug ADME

MSigDB gene sets: 94 (showing top): GNF2_GSTM1, GNF2_HPN, CCATCCA_MIR432, GOBP_ORGANIC_ACID_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GNF2_LCAT, CAIRO_HEPATOBLASTOMA_DN, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_DICARBOXYLIC_ACID_TRANSPORT, GNF2_HPX, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_LIPID_LOCALIZATION, GOBP_FATTY_ACID_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (6): xenobiotic metabolic process (GO:0006805), monoatomic ion transport (GO:0006811), obsolete organic anion transport (GO:0015711), prostaglandin transport (GO:0015732), alpha-ketoglutarate transport (GO:0015742), transmembrane transport (GO:0055085)

GO Molecular Function (6): obsolete organic anion transmembrane transporter activity (GO:0008514), prostaglandin transmembrane transporter activity (GO:0015132), alpha-ketoglutarate transmembrane transporter activity (GO:0015139), obsolete sodium-independent organic anion transmembrane transporter activity (GO:0015347), transmembrane transporter activity (GO:0022857), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SLC-mediated transport of organic anions	1
Drug ADME	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
plasma membrane region	3
transport	2
metabolic process	1
cellular response to xenobiotic stimulus	1
fatty acid transport	1
icosanoid transport	1
dicarboxylic acid transport	1
cellular process	1
prostaglandin transport	1
icosanoid transmembrane transporter activity	1
dicarboxylic acid transmembrane transporter activity	1
alpha-ketoglutarate transport	1
transporter activity	1
transmembrane transport	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
basal part of cell	1
basal plasma membrane	1
apical part of cell	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A7	SLCO1B1	Q9Y6L6	958
SLC22A7	SLCO1B3	Q9NPD5	958
SLC22A7	SLCO1A2	P46721	855
SLC22A7	ABCC4	O15439	807
SLC22A7	SLCO2B1	O94956	767
SLC22A7	SLC47A1	Q96FL8	729
SLC22A7	SLC47A2	Q86VL8	709
SLC22A7	SLC10A1	Q14973	707
SLC22A7	SLCO4C1	Q6ZQN7	667
SLC22A7	ABCG2	Q9UNQ0	658
SLC22A7	ABCC3	O15438	635
SLC22A7	ABCB11	O95342	634
SLC22A7	ABCC2	Q92887	627
SLC22A7	SLC15A1	P46059	593
SLC22A7	SLCO4A1	Q96BD0	578

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC22A7	RAPGEF4	psi-mi:“MI:0915”(physical association)	0.370
SLC22A7	PGRMC2	psi-mi:“MI:0914”(association)	0.350
	GLRX3	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): ARF4 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), CLPTM1 (Affinity Capture-MS), DNAJB12 (Affinity Capture-MS), ERLIN1 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), FAF2 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), RPL12 (Affinity Capture-MS), RPS27 (Affinity Capture-MS), RPS27L (Affinity Capture-MS), STX17 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), UGGT1 (Affinity Capture-MS)

ESM2 similar proteins: A6NK97, A6QLW8, A7MBE0, A9CB25, B2GV36, O15245, O35956, O57379, O75751, O88446, O88909, Q1RPP5, Q3YAW7, Q4U2R8, Q4W8A2, Q4W8A3, Q5NCM1, Q5R540, Q5R9C4, Q5RCH6, Q5RLM2, Q66J52, Q66J54, Q6A4L0, Q6DFR1, Q6NUB3, Q6NWF1, Q6NYN7, Q70BM6, Q80UJ1, Q863T6, Q864Z3, Q86VW1, Q8HY24, Q8MK48, Q8R0S9, Q8TCC7, Q8VC69, Q91WU2, Q9H015

Diamond homologs: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, B2GV36, G1SZD9, O34691, O35956, O57379, O75751, O88446, O88909, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R540, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63ZE4, Q66J52, Q66J54, Q6A4L0, Q6NYN7, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

64 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1583 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43298542:G:GT	donor_gain	1.0000
6:43299885:T:TA	acceptor_gain	1.0000
6:43299890:T:A	acceptor_gain	1.0000
6:43299891:G:A	acceptor_gain	1.0000
6:43299896:A:AG	acceptor_gain	1.0000
6:43299897:G:GG	acceptor_gain	1.0000
6:43301690:GTG:G	donor_gain	1.0000
6:43301698:G:GT	donor_gain	1.0000
6:43302761:CAGGT:C	donor_loss	1.0000
6:43302762:AGGT:A	donor_loss	1.0000
6:43302763:GG:G	donor_loss	1.0000
6:43302764:GTGA:G	donor_loss	1.0000
6:43302765:T:G	donor_loss	1.0000
6:43304669:A:AG	acceptor_gain	1.0000
6:43304670:G:GG	acceptor_gain	1.0000
6:43298709:G:GT	donor_gain	0.9900
6:43298748:TGAG:T	donor_loss	0.9900
6:43298750:AGG:A	donor_loss	0.9900
6:43298752:G:T	donor_loss	0.9900
6:43299388:AGTG:A	acceptor_gain	0.9900
6:43299388:AGTGG:A	acceptor_gain	0.9900
6:43299389:GTGG:G	acceptor_gain	0.9900
6:43299389:GTGGG:G	acceptor_gain	0.9900
6:43299624:CA:C	acceptor_loss	0.9900
6:43299625:A:AT	acceptor_loss	0.9900
6:43299626:G:GT	acceptor_loss	0.9900
6:43299626:GGTTT:G	acceptor_gain	0.9900
6:43299661:G:GG	donor_gain	0.9900
6:43299705:C:G	donor_gain	0.9900
6:43299894:CCA:C	acceptor_loss	0.9900

AlphaMissense

3442 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43298709:G:C	W117C	0.991
6:43298709:G:T	W117C	0.991
6:43299392:G:C	W134C	0.990
6:43299392:G:T	W134C	0.990
6:43298503:T:A	C49S	0.988
6:43298504:G:C	C49S	0.988
6:43299451:G:A	G154D	0.988
6:43299906:T:A	W223R	0.988
6:43299906:T:C	W223R	0.988
6:43302763:G:C	R462T	0.988
6:43299740:G:A	G206D	0.987
6:43299728:G:C	R202P	0.986
6:43299903:G:A	E222K	0.986
6:43301149:C:T	S281F	0.985
6:43299948:A:C	S237R	0.984
6:43299950:C:A	S237R	0.984
6:43299950:C:G	S237R	0.984
6:43302714:T:C	F446L	0.984
6:43302716:C:A	F446L	0.984
6:43302716:C:G	F446L	0.984
6:43304038:A:C	R462S	0.983
6:43304038:A:T	R462S	0.983
6:43298695:T:A	C113S	0.982
6:43298696:G:C	C113S	0.982
6:43299402:T:A	C138S	0.982
6:43299403:G:C	C138S	0.982
6:43300010:G:C	W257C	0.982
6:43300010:G:T	W257C	0.982
6:43302763:G:T	R462I	0.982
6:43299403:G:A	C138Y	0.981

dbSNP variants (sampled 300 via entrez): RS1000109187 (6:43304762 A>C), RS1000227416 (6:43301500 A>G), RS1000285504 (6:43293924 T>C), RS1000561772 (6:43299748 C>T), RS1000698327 (6:43294402 C>A,T), RS1000801585 (6:43299537 T>C), RS1000843279 (6:43299197 G>C), RS1001500159 (6:43302943 G>A), RS1001798995 (6:43294747 C>T), RS1002074211 (6:43300262 G>A), RS1002108065 (6:43298108 C>G,T), RS1002141973 (6:43301759 T>C), RS1002805473 (6:43296203 C>A,T), RS1004028981 (6:43296983 G>A,T), RS1004699460 (6:43303839 G>A)

Disease associations

OMIM: gene MIM:604995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST001791_13	Urate levels	1.000000e-06
GCST003272_2	Systolic blood pressure	2.000000e-16
GCST004521_164	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004775_24	Pulse pressure	7.000000e-07
GCST004776_25	Systolic blood pressure	3.000000e-06
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31
GCST005978_10	Diastolic blood pressure	3.000000e-08
GCST005979_13	Systolic blood pressure	9.000000e-13
GCST006010_9	Mean arterial pressure	1.000000e-11
GCST006187_16	Diastolic blood pressure (cigarette smoking interaction)	4.000000e-11
GCST006188_31	Systolic blood pressure (cigarette smoking interaction)	8.000000e-23
GCST006228_5	Systolic blood pressure	3.000000e-11
GCST006230_3	Pulse pressure	5.000000e-09
GCST007703_135	Systolic blood pressure	1.000000e-10
GCST007703_99	Systolic blood pressure	1.000000e-10
GCST007704_44	Diastolic blood pressure	3.000000e-07
GCST007704_48	Diastolic blood pressure	5.000000e-07
GCST007705_68	Pulse pressure	4.000000e-06
GCST007705_8	Pulse pressure	3.000000e-06
GCST007706_36	Mean arterial pressure	1.000000e-09
GCST007706_83	Mean arterial pressure	1.000000e-09
GCST007707_33	Hypertension	1.000000e-07
GCST007707_48	Hypertension	2.000000e-07
GCST008899_1	Adult hearing difficulty	6.000000e-21
GCST008971_56	Urate levels	3.000000e-14
GCST008972_30	Urate levels	5.000000e-30
GCST010167_3	Cardioembolic stroke (CCSc classification)	4.000000e-06

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006527	smoking status measurement
EFO:1001976	cardioembolic stroke
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1955711 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2270860	Toxicity	3	capecitabine	Drug Toxicity;Neoplasms
rs4149178	Toxicity	3	capecitabine	Diarrhea;Neoplasms

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4149178	SLC22A7	3	2.75	1	capecitabine
rs2270860	SLC22A7	3	2.75	1	capecitabine

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Organic anion transporters (OATs)

CTD chemical–gene interactions

92 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases activity, decreases expression, decreases reaction, increases transport	4
Benzo(a)pyrene	decreases expression, increases methylation	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	4
Aflatoxin B1	affects expression, decreases expression	3
Chenodeoxycholic Acid	decreases expression, affects cotreatment	2
Diclofenac	decreases reaction, increases transport, decreases activity	2
Ibuprofen	increases transport, decreases activity, decreases reaction	2
Indomethacin	decreases reaction, increases transport, decreases activity	2
Methotrexate	increases expression, increases uptake	2
p-Aminohippuric Acid	increases uptake	2
Rifampin	decreases expression	2
Tetracycline	decreases reaction, increases transport, increases uptake	2
Valproic Acid	affects expression, decreases expression	2
Zidovudine	increases uptake, increases expression	2
Cyclosporine	decreases expression	2
Salicylic Acid	increases export, increases reaction, decreases activity, increases uptake	2
methyleugenol	decreases expression	1
bisphenol A	affects expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
estrone sulfate	increases uptake, increases reaction	1
sodium arsenite	decreases expression	1
oltipraz	decreases expression	1
cinnamic acid	increases export, increases reaction	1
phenylpyruvic acid	increases export, increases reaction	1
tebuconazole	decreases expression	1
GW 501516	affects binding, increases expression	1
Rosiglitazone	decreases expression	1

ChEMBL screening assays

24 unique, capped per target: 18 functional, 5 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1959693	Binding	Activity at OAT2	Discovery of GS-9256: a novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity. — Bioorg Med Chem Lett
CHEMBL2075459	Functional	TP_TRANSPORTER: inhibition of PGF2alpha uptake (PGF2alpha: 0.05 uM, PGE2: 30 uM) in OAT2-expressing S2 cells	Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. — J Pharmacol Exp Ther
CHEMBL3528449	ADMET	Drug transport in human OAT2 expressed in HEK Flp-In cells at 0.05 uM for 10 mins relative to control	Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. — Drug Metab Dispos

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4SC	HuH7-SLC22A7-KO-c2	Cancer cell line	Male
CVCL_D4SD	HuH7-SLC22A7-KO-c6	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.