SLC23A1

Summary

SLC23A1 (solute carrier family 23 member 1, HGNC:10974) is a protein-coding gene on chromosome 5q31.2, encoding Solute carrier family 23 member 1 (Q9UHI7). Sodium:ascorbate cotransporter.

The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two transporters. The encoded protein is active in bulk vitamin C transport involving epithelial surfaces. Previously, this gene had an official symbol of SLC23A2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9963 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 88 total
• Druggable target: yes
• MANE Select transcript: NM_005847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10974
Approved symbol	SLC23A1
Name	solute carrier family 23 member 1
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	YSPL3, SVCT1
Ensembl gene	ENSG00000170482
Ensembl biotype	protein_coding
OMIM	603790
Entrez	9963

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000348729, ENST00000353963, ENST00000502863, ENST00000503919, ENST00000504513, ENST00000506512, ENST00000508270, ENST00000882127, ENST00000882128, ENST00000882129

RefSeq mRNA: 2 — MANE Select: NM_005847 NM_005847, NM_152685

CCDS: CCDS4212, CCDS4213

Canonical transcript exons

ENST00000348729 — 15 exons

Exon	Start	End
ENSE00001128394	139380208	139380389
ENSE00001385108	139380565	139380632
ENSE00001812424	139367196	139367631
ENSE00001942742	139383218	139383297
ENSE00002224824	139379678	139379834
ENSE00002294049	139379207	139379354
ENSE00002455523	139377402	139377497
ENSE00002476116	139371987	139372253
ENSE00002481803	139377975	139378118
ENSE00002492742	139378579	139378684
ENSE00002504988	139378222	139378351
ENSE00003495908	139380798	139380886
ENSE00003572999	139381892	139382049
ENSE00003634444	139379956	139380076
ENSE00003643695	139382492	139382605

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 98.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1613 / max 52.9132, expressed in 43 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63738	0.4576	68
63737	0.0708	26
63740	0.0555	23
63739	0.0349	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.90	gold quality
right uterine tube	UBERON:0001302	98.68	gold quality
kidney epithelium	UBERON:0004819	98.20	gold quality
jejunal mucosa	UBERON:0000399	93.50	gold quality
right lobe of liver	UBERON:0001114	89.49	gold quality
oviduct epithelium	UBERON:0004804	87.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.78	gold quality
duodenum	UBERON:0002114	86.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.70	gold quality
mucosa of transverse colon	UBERON:0004991	85.43	gold quality
adult mammalian kidney	UBERON:0000082	85.33	gold quality
small intestine	UBERON:0002108	84.43	gold quality
liver	UBERON:0002107	84.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.89	silver quality
fallopian tube	UBERON:0003889	82.91	gold quality
kidney	UBERON:0002113	81.46	gold quality
bronchial epithelial cell	CL:0002328	81.21	gold quality
bronchus	UBERON:0002185	79.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.56	gold quality
cortex of kidney	UBERON:0001225	77.65	gold quality
metanephros cortex	UBERON:0010533	72.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.90	gold quality
adult organism	UBERON:0007023	71.86	gold quality
gall bladder	UBERON:0002110	70.07	gold quality
transverse colon	UBERON:0001157	69.95	gold quality
jejunum	UBERON:0002115	69.78	gold quality
bone marrow cell	CL:0002092	69.77	silver quality
prostate gland	UBERON:0002367	69.45	gold quality
sural nerve	UBERON:0015488	68.20	gold quality
intestine	UBERON:0000160	67.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting SLC23A1, 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-4682	100.00	68.89	1258
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-934	98.49	70.44	581
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-1178-5P	95.83	64.12	504
HSA-MIR-4474-5P	94.23	67.95	568
HSA-MIR-6789-5P	94.05	66.19	285

Literature-anchored findings (GeneRIF, showing 38)

• SVCT1 is the transporter that allows vectorial uptake of ascorbic acid in differentiated CaCo-2 cells (PMID:12381735)
• Results provide the first direct resolution of functional hSVCT1 expression at the apical cell surface of polarized epithelia and define an apical targeting signal of relevance to transporters of diverse substrate specificity. (PMID:15084584)
• Functionally, SVCT1 expression led to more transport activity from the apical membrane, while SVCT2 expression only increased the uptake under the condition when basolateral membrane was exposed. (PMID:15993839)
• Findings link genetic variants in the vitamin C transporter gene SLC23A1 to spontaneous preterm birth. (PMID:16357110)
• C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production (PMID:17008880)
• SVCT1 is responsible for epidermal ascorbic acid supply, whereas SVCT2 mainly facilitates ascorbic acid transport in the dermal compartment (PMID:17664139)
• We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease. (PMID:18094143)
• The results suggest that uncharged His51 of hSVCT1, directly or indirectly, contributes to substrate binding through the hydrogen bond. (PMID:18247577)
• SVCT1 may be targeted to facilitate the delivery of drugs with low bioavailability by conjugating with ascorbic acid (PMID:18417304)
• N-Glycosylation is therefore essential for SVCT1 functionality. (PMID:18619416)
• estrogen receptor 1, vitamin C receptors SLC23A1 and SLC23A2, and matrix metalloproteinase MMP3 and MMP9 are associated with susceptibility to lymphoma (PMID:18636124)
• The analysis of common single nucleotide polymorphisms in SLC23A1 revealed no association with colorectal adenoma risk. (PMID:18791929)
• Results using short interfering RNA suggest that in HepG2 cells, decreasing hSVCT2 message levels reduces the overall ascorbic acid uptake process more than decreasing hSVCT1 message levels. (PMID:18845575)
• These results collectively suggested a default apical targeting of SVCT, which is consistent with the evolution-based prediction. (PMID:19216494)
• common variants in SLC23A2, a gene that directly regulates active transport of ascorbic acid, can impact gastric cancer risk (PMID:19243932)
• Results describe the membrane topology of human SVCT1 and SVCT2, and the role of glycosylation on protein transport. (PMID:19379732)
• HNF-1alpha and/or HNF-1beta binding is required for SVCT1 expression (PMID:19741195)
• hSVCT1 and 2 promoters establish that ascorbic acid uptake by human liver epithelial cells is adaptively regulated and show that transcriptional mechanisms via HNF-1 in the hSVCT1 promoter may, in part, be involved in this regulation. (PMID:20471816)
• A genetic variant (rs33972313) in the SLC23A1 vitamin C active transporter locus was identified that is reliably associated with circulating concentrations of L-ascorbic acid in the general population. (PMID:20519558)
• In patients with hepatocellular cholestasis, primary biliary cirrhosis, haemochromatosis and non-alcoholic steatohepatitis, using real-time RT-PCR, an enhanced hepatic expression of both SLC23A1 and SLC23A2 was found. (PMID:21733302)
• glutathione depletion failed to affect ascorbic acid transport, and SVCT1 and SVCT2 expression in hepatoma cells. Therefore, our data indicate an essential role for glutathione in controlling vitamin C metabolism in rat hepatocytes and rat hepatoma cells (PMID:22348976)
• The SVCT1 was induced and localized to the apical membrane of tubular epithelial cells. (PMID:22990596)
• These findings show a role for Rab8a in the physiological function of SVCT1 in intestinal epithelia. (PMID:23014846)
• SVCT1 directly interacts with GRHPR. (PMID:23599041)
• Data show that the mRNA level of svct2 was approximately 600- to 900-fold higher than that of svct1 indicating SVCT2 is a main isoform in fibroblast OUMS-36 cells, and no significant difference in svct2 mRNA and protein between young and old cells. (PMID:23613229)
• Data suggest that N-terminal and C-terminal sorting signals interact, directly or indirectly, within each gene family (here, SVCT1 and SVCT2) in basolateral targeting of transmembrane proteins to basolateral cell membrane. (PMID:23837633)
• A genetic variant in the SLC23A1 ascorbate transporter locus was identified and is associated with an increased risk of Crohn disease in a white Canadian inflammatory bowel diseases cohort. (PMID:24284447)
• SNP rs6596473 of SLC23A1 is suggested to be associated with AgP. results add to previous reports vitamin C plays a role in pathogenesis of periodontitis. (PMID:24708273)
• polymorphisms in SLC23A1/2 genes influenced ascorbate concentration in aqueous humor and lens nucleus. (PMID:24815519)
• Data from observational/genetic association studies in Europe suggest an SNP in SLC23A1 (rs33972313) is associated with up-regulation of circulating L-ascorbic acid but not with any cardiometabolic/cardiovascular outcome investigated. [META-ANALYSIS] (PMID:25527764)
• consensus site for HNF1 that is crucial for the regulation of the human SVCT1 promoter is present in the SVCT1 rat promoter but has no effect on its transcriptional activity (PMID:25933589)
• Our findings show, for the first time, that transporters of the water-soluble vitamin ascorbic acid (i.e., the vitamin C transporters SVCT-1 and SVCT-2) are differentially expressed along the length of the intestinal tract and that the pattern of expression is mediated, at least in part, by transcriptional and epigenetic mechanism(s) affecting both Slc23a1 and Slc23a2 genes. (PMID:27932501)
• Posttranscriptional regulation of SVCT1 by miRNA in intestinal epithelial cells.Mir-103a target SVCT1 3’-UTR and regulates SVCT1 expression. (PMID:30616065)
• Limited Association Between Ascorbate Concentrations and Vitamin C Transporters in Renal Cell Carcinoma Cells and Clinical Samples. (PMID:34599650)
• Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study. (PMID:34780525)
• Impact of SLC23A1 and SLC23A2 Polymorphisms on the Risk for Preeclampsia in a Chinese Han Population. (PMID:36310070)
• Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations. (PMID:36749388)
• Dimeric transport mechanism of human vitamin C transporter SVCT1. (PMID:38956111)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc23a1	ENSDARG00000015033
mus_musculus	Slc23a1	ENSMUSG00000024354
rattus_norvegicus	Slc23a1	ENSRNOG00000061695
drosophila_melanogaster	CG6293	FBGN0037807

Paralogs (2): SLC23A2 (ENSG00000089057), SLC23A3 (ENSG00000213901)

Protein

Protein identifiers

Solute carrier family 23 member 1 — Q9UHI7 (reviewed: Q9UHI7)

Alternative names: Na(+)/L-ascorbic acid transporter 1, Sodium-dependent vitamin C transporter 1, Yolk sac permease-like molecule 3

All UniProt accessions (3): Q9UHI7, H0Y902, H0YAJ1

UniProt curated annotations — full annotation on UniProt →

Function. Sodium:ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate. Has retained some ancestral activity toward nucleobases such as urate, an oxidized purine. Low-affinity high-capacity sodium:urate cotransporter, may regulate serum urate levels by serving as a renal urate re-absorber. Inactive transporter.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in adult small intestine, kidney, thymus, ovary, colon, prostate and liver, and in fetal kidney, liver and thymus.

Post-translational modifications. Phosphorylated.

Miscellaneous. Treatment with the protein kinase C stimulator PMA results in a 10-fold decrease in ascorbate accumulation in transfected cells.

Similarity. Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UHI7-1	1	yes
Q9UHI7-2	2
Q9UHI7-3	3

RefSeq proteins (2): NP_005838, NP_689898 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006043	NCS2	Family

Pfam: PF00860

Catalyzed reactions (Rhea), 2 shown:

• L-ascorbate(out) + 2 Na(+)(out) = L-ascorbate(in) + 2 Na(+)(in) (RHEA:69883)
• urate(out) + 2 Na(+)(out) = urate(in) + 2 Na(+)(in) (RHEA:76339)

UniProt features (96 total): helix 27, sequence conflict 15, topological domain 14, transmembrane region 12, turn 7, sequence variant 4, strand 4, modified residue 3, region of interest 2, compositionally biased region 2, glycosylation site 2, splice variant 2, chain 1, intramembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8JEW	ELECTRON MICROSCOPY	2.49
8JEZ	ELECTRON MICROSCOPY	2.6
8JF1	ELECTRON MICROSCOPY	2.85
8JF0	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHI7-F1	81.74	0.43

Functional residue map

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

Post-translational modifications (3): 591, 593, 596

Glycosylation sites (2): 138, 144

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196836	Vitamin C (ascorbate) metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 338 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_RESPONSE_TO_ETHANOL, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (12): sodium ion transport (GO:0006814), brain development (GO:0007420), response to toxic substance (GO:0009636), nucleobase transport (GO:0015851), L-ascorbic acid transmembrane transport (GO:0015882), L-ascorbic acid metabolic process (GO:0019852), lung development (GO:0030324), dehydroascorbic acid transport (GO:0070837), monoatomic ion transport (GO:0006811), urate transport (GO:0015747), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (9): L-ascorbate:sodium symporter activity (GO:0008520), sodium ion transmembrane transporter activity (GO:0015081), urate transmembrane transporter activity (GO:0015143), nucleobase transmembrane transporter activity (GO:0015205), L-ascorbic acid transmembrane transporter activity (GO:0015229), dehydroascorbic acid transmembrane transporter activity (GO:0033300), protein binding (GO:0005515), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (7): cytoplasm (GO:0005737), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), apical plasma membrane (GO:0016324), intracellular organelle (GO:0043229), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
nitrogen compound transport	2
transport	2
monosaccharide transmembrane transporter activity	2
carboxylic acid transmembrane transporter activity	2
vitamin transmembrane transporter activity	2
intracellular anatomical structure	2
cellular anatomical structure	2
plasma membrane region	2
metal ion transport	1
central nervous system development	1
head development	1
response to chemical	1
monosaccharide transmembrane transport	1
vitamin transmembrane transport	1
carboxylic acid transmembrane transport	1
monosaccharide metabolic process	1
carboxylic acid metabolic process	1
lactone metabolic process	1
respiratory tube development	1
respiratory system development	1
vitamin transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
cellular process	1
organic acid:sodium symporter activity	1
carbohydrate:monoatomic cation symporter activity	1
sodium ion transmembrane transport	1
metal ion transmembrane transporter activity	1
urate transport	1
salt transmembrane transporter activity	1
nucleobase transport	1
transmembrane transporter activity	1
L-ascorbic acid transmembrane transport	1
dehydroascorbic acid transport	1
binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1

Protein interactions and networks

STRING

1450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC23A1	MATR3	P43243	841
SLC23A1	SFTPB	P07988	662
SLC23A1	SLC2A3	P11169	584
SLC23A1	SLC2A1	P11166	537
SLC23A1	SLC52A1	Q9NWF4	460
SLC23A1	SLC44A4	Q53GD3	458
SLC23A1	SLC5A6	Q9Y289	454
SLC23A1	SLC6A20	Q9NP91	447
SLC23A1	SIL1	Q9H173	446
SLC23A1	SLC2A8	Q9NY64	433
SLC23A1	SLC5A8	Q8N695	431
SLC23A1	SLC2A12	Q8TD20	429
SLC23A1	GATA1	P15976	427
SLC23A1	SLC7A6	Q92536	426
SLC23A1	SLC2A2	P11168	419

IntAct

153 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	SLC23A1	psi-mi:“MI:0915”(physical association)	0.670
SLC23A1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.670
GRHPR	SLC23A1	psi-mi:“MI:0915”(physical association)	0.630
GRHPR	SLC23A1	psi-mi:“MI:0403”(colocalization)	0.630
AHCYL1	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
SLC23A1	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
SLC23A1	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
KRT31	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
SLC23A1	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
SLC23A1	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-2	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
SLC23A1		psi-mi:“MI:0915”(physical association)	0.560
SLC23A1	AHCYL1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	SLC23A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (57): SLC23A1 (Two-hybrid), AHCYL1 (Two-hybrid), MTUS2 (Two-hybrid), ADAMTSL4 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), KRTAP10-8 (Two-hybrid), SLC23A1 (Two-hybrid), SLC23A1 (Two-hybrid)

ESM2 similar proteins: A2AJN7, A2AWR3, E9Q3M5, O13134, O22881, O88343, P02730, P23562, Q28677, Q2UVJ5, Q2Y0W8, Q32LP4, Q3E954, Q3TWI9, Q4U116, Q53P98, Q5DTL9, Q5R9A7, Q5RK27, Q63632, Q63633, Q657W3, Q6RI88, Q6RVG2, Q6U841, Q6Z0E2, Q7YRU6, Q7Z3F1, Q80ZA5, Q8JZR6, Q8NBS3, Q8VYR7, Q91V14, Q924N4, Q9GL77, Q9H2X9, Q9JI66, Q9JIS8, Q9M1P7, Q9SSG5

Diamond homologs: B0JZG0, O04472, P93039, Q0WPE9, Q27GI3, Q3E7D0, Q41760, Q60850, Q6PIS1, Q6SZ87, Q8GZD4, Q8RWE9, Q8VZQ5, Q94C70, Q9EPR4, Q9SHZ3, Q9UGH3, Q9UHI7, Q9WTW7, Q9WTW8, Q9Z2J0, Q3E956, A0A2A5K1W4, O32139, P0AGM7, P0AGM8, P39766, P41006, P45117, P75892, Q9CPL9, P50487, P42086

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	46.0×	5e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	5e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	5e-06
Assembly and cell surface presentation of NMDA receptors	10	40.9×	5e-12
Dopamine Neurotransmitter Release Cycle	5	40.0×	7e-06
Long-term potentiation	5	38.4×	7e-06
Neurexins and neuroligins	11	34.9×	3e-12
Protein-protein interactions at synapses	7	30.0×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	64.6×	4e-12
protein localization to synapse	6	56.7×	1e-07
receptor clustering	7	53.9×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	36.7×	1e-06
cell-cell adhesion	9	11.3×	7e-06
protein-containing complex assembly	8	11.2×	3e-05
chemical synaptic transmission	7	6.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3876 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139379277:A:G	S335P	1.000
5:139372238:C:G	R522P	0.999
5:139378100:C:T	G443E	0.999
5:139378101:C:A	G443W	0.999
5:139378101:C:G	G443R	0.999
5:139378101:C:T	G443R	0.999
5:139378603:G:C	N385K	0.999
5:139378603:G:T	N385K	0.999
5:139378609:A:C	S383R	0.999
5:139378609:A:T	S383R	0.999
5:139378611:T:G	S383R	0.999
5:139378668:C:A	G364C	0.999
5:139378668:C:G	G364R	0.999
5:139378682:C:T	G359D	0.999
5:139378683:C:G	G359R	0.999
5:139379252:G:T	A343D	0.999
5:139379270:C:T	G337E	0.999
5:139379276:G:A	S335F	0.999
5:139379302:G:C	S326R	0.999
5:139379302:G:T	S326R	0.999
5:139379304:T:G	S326R	0.999
5:139380274:A:G	L194P	0.999
5:139372236:C:G	G523R	0.998
5:139377416:T:A	D512V	0.998
5:139377417:C:G	D512H	0.998
5:139378043:C:T	G462E	0.998
5:139378044:C:G	G462R	0.998
5:139378044:C:T	G462R	0.998
5:139378057:G:C	N457K	0.998
5:139378057:G:T	N457K	0.998

dbSNP variants (sampled 300 via entrez): RS1000142384 (5:139375987 A>C), RS1000685694 (5:139370543 G>A), RS1000888807 (5:139387494 T>C), RS1001092691 (5:139382109 G>A), RS1001285683 (5:139369985 A>G), RS1001472147 (5:139375478 C>G), RS1001667426 (5:139383445 A>C), RS1001833857 (5:139382151 C>A,T), RS1001861383 (5:139370188 G>A), RS1001949224 (5:139382355 C>A,T), RS1002221997 (5:139381836 G>A,C), RS1002297125 (5:139381570 G>A), RS1002649825 (5:139373985 T>C), RS1003047112 (5:139385035 G>A), RS1003143591 (5:139368096 G>A)

Disease associations

OMIM: gene MIM:603790 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5209632 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC23 family of ascorbic acid transporters

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
phloretin	Inhibition	4.19	pKi

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ascorbic Acid	increases expression, decreases expression, decreases reaction, increases transport, affects abundance (+1 more)	4
Cyclosporine	decreases expression	4
Benzo(a)pyrene	affects methylation, decreases expression	3
Aflatoxin B1	affects methylation, decreases expression, affects expression	3
bisphenol A	increases abundance, decreases expression, increases expression, decreases reaction	2
Quercetin	decreases reaction, increases transport, decreases expression	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
ginger extract	increases expression, decreases reaction, increases abundance	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	affects methylation	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
6-deoxy-6-bromoascorbic acid	affects transport	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Aldehydes	decreases expression	1
Bilirubin	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	decreases expression	1
Methapyrilene	affects methylation	1
Oils, Volatile	decreases reaction, increases abundance, increases expression	1
Silicon Dioxide	decreases expression	1
Taurocholic Acid	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5209615	Functional	Substrate uptake and inhibition of the Na(+)/L-Ascorbic Acid Transporter 1 (SVCT1, SLC23A1) as assessed by the fluorescent FLIPR membrane potential dye in HEK-293 JumpIN-SLC23A1 cells (PubChem AID: 1794810)	Membrane potential based assay for SLC23A1 using HEK-293 SLC23A1 OE cells

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4SG	HuH7-SLC23A1-KO-c2	Cancer cell line	Male
CVCL_D4SH	HuH7-SLC23A1-KO-c3	Cancer cell line	Male

Clinical trials (associated diseases)

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