SLC23A2

Summary

SLC23A2 (solute carrier family 23 member 2, HGNC:10973) is a protein-coding gene on chromosome 20p13, encoding Solute carrier family 23 member 2 (Q9UGH3). 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 required transporters and the encoded protein accounts for tissue-specific uptake of vitamin C. Previously, this gene had an official symbol of SLC23A1.

Source: NCBI Gene 9962 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 162 total
• Druggable target: yes
• MANE Select transcript: NM_005116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10973
Approved symbol	SLC23A2
Name	solute carrier family 23 member 2
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	SVCT2, KIAA0238, YSPL2
Ensembl gene	ENSG00000089057
Ensembl biotype	protein_coding
OMIM	603791
Entrez	9962

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000338244, ENST00000379333, ENST00000423430, ENST00000468355, ENST00000496331, ENST00000877967, ENST00000877968, ENST00000877969, ENST00000877970, ENST00000877971, ENST00000877972, ENST00000877973, ENST00000877974, ENST00000922620, ENST00000922621, ENST00000922622, ENST00000949265, ENST00000949266, ENST00000949267, ENST00000949268

RefSeq mRNA: 2 — MANE Select: NM_005116 NM_005116, NM_203327

CCDS: CCDS13085

Canonical transcript exons

ENST00000338244 — 17 exons

Exon	Start	End
ENSE00001373320	5001406	5001510
ENSE00001386311	4970793	4970919
ENSE00001600214	4862778	4862907
ENSE00001657870	4859289	4859384
ENSE00001741906	4869906	4870053
ENSE00001757600	4861948	4862085
ENSE00001760817	4867770	4867875
ENSE00003460584	4874576	4874696
ENSE00003511070	4912880	4912978
ENSE00003517528	4885821	4885909
ENSE00003521585	4873936	4874092
ENSE00003595241	4902442	4902558
ENSE00003615273	4899555	4899712
ENSE00003623135	4932455	4932716
ENSE00003648004	4883642	4883823
ENSE00003648773	4884753	4884823
ENSE00003849077	4852358	4857204

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4576 / max 160.7702, expressed in 68 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186259	12.0312	1774
186257	0.8309	401
186258	0.7369	413
63738	0.4576	68
186263	0.1904	68
186260	0.1625	73
186262	0.0937	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.93	gold quality
right adrenal gland cortex	UBERON:0035827	96.83	gold quality
adrenal cortex	UBERON:0001235	96.52	gold quality
left adrenal gland cortex	UBERON:0035825	96.28	gold quality
left adrenal gland	UBERON:0001234	95.94	gold quality
adrenal gland	UBERON:0002369	95.83	gold quality
right adrenal gland	UBERON:0001233	95.80	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.31	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.40	gold quality
choroid plexus epithelium	UBERON:0003911	92.98	gold quality
paraflocculus	UBERON:0005351	92.47	gold quality
cerebellar vermis	UBERON:0004720	92.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.42	gold quality
substantia nigra pars compacta	UBERON:0001965	92.38	gold quality
right lobe of liver	UBERON:0001114	92.18	gold quality
cortical plate	UBERON:0005343	92.07	gold quality
subthalamic nucleus	UBERON:0001906	91.97	gold quality
left ovary	UBERON:0002119	91.73	gold quality
middle frontal gyrus	UBERON:0002702	91.47	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.40	gold quality
pigmented layer of retina	UBERON:0001782	91.36	gold quality
postcentral gyrus	UBERON:0002581	91.20	gold quality
frontal pole	UBERON:0002795	91.16	gold quality
spinal cord	UBERON:0002240	91.00	gold quality
parietal lobe	UBERON:0001872	90.98	gold quality
ventral tegmental area	UBERON:0002691	90.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.84	gold quality
medulla oblongata	UBERON:0001896	90.82	gold quality
prefrontal cortex	UBERON:0000451	90.72	gold quality
right ovary	UBERON:0002118	90.67	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	17.16
E-GEOD-135922	yes	13.27
E-MTAB-6142	no	158.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

256 targeting SLC23A2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• These findings suggest a mechanism of ascorbic acid uptake regulation whereby an alternative sodium-ascorbate cotransporter 2 (SVCT2) gene product inhibits transport through the two known ascorbic acid transporters. (PMID:15060139)
• Functionally expressed in human endothelial cells and negatively regulated by inflammatory cytokines. May provide new insight into treatment of cardiovascular diseases with ascorbic acid. (PMID:15340249)
• SVCT2 mediates the secondary active and concentrative transport of ascorbic acid in human chondrocytes (PMID:15921655)
• 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 SLC23A2 to spontaneous preterm birth. (PMID:16357110)
• The promoter functionality of the two genomic regions of the hSVCT2 upstream of these alternative first exons in human Vascular Smooth Muscle Cells was tested. (PMID:16380174)
• SVCT2 may switch between a number of states with characteristic properties, including an inactive conformation in the absence of Ca(2+)/Mg(2+) (PMID:17012227)
• SVCT2 mRNA expression in human first-trimester chorionic villi but not in term placental tissue. (PMID:17092984)
• SVCT2 expression can be regulated at the translational level by ascorbic acid and the redox state. (PMID:17291984)
• SVCT1 is responsible for epidermal ascorbic acid supply, whereas SVCT2 mainly facilitates ascorbic acid transport in the dermal compartment (PMID:17664139)
• The results suggest that uncharged His109 of hSVCT2, directly or indirectly, contributes to substrate binding through the hydrogen bond. (PMID:18247577)
• all three proximal tubule segments expressed the transporter but the S3 segment had the highest expression; Ascorbic acid transport in these cells was regulated by a single kinetic component that depended on the sodium concentration, pH and temperature (PMID:18614995)
• N-Glycosylation is therefore essential for SVCT2 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)
• For SLC23A2, overall, there was no colorectal adenoma association with haplotypes, but two SNPs located in intron 8 and exon 11 could be associated (odds ratio = 0.49, 95% confidence interval = 0.25-0.95 for haplotype G-C vs. haplotype C-C). (PMID:18791929)
• hSVCT2 protein and mRNA are expressed at higher levels in HepG2 cells and native human liver, and the cloned hSVCT2 promoter has more activity in HepG2 cells. (PMID:18845575)
• transports Vitamin C, a vital antioxidant, into the brain (PMID:19162177)
• These results collectively suggested a default apical targeting of SVCT, which is consistent with the evolution-based prediction. (PMID:19216494)
• increased expression during macrophage differentiation (PMID:19232538)
• common variants in SLC23A2, a gene that directly regulates active transport of ascorbic acid, can impact gastric cancer risk (PMID:19243932)
• SLC23A2 genetic variation alters HPV16-associated HNSCC while also highlighting the important role of citrus exposure in this disease. (PMID:19346260)
• both NH(2)- and COOH-terminal sequences are essential for proper localization of hSVCT2, cell surface delivery is dependent on intact microtubules, and peripheral microfilaments regulate insertion and retrieval of hSVCT2 into the plasma membrane (PMID:19926816)
• 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)
• Differential occupancy of transcription factors on the GC-rich consensus sequences in the sodium-dependent vitamin C transporter (SVCT2) exon 1b promoter contributes to the regulation of cell and tissue expression of SVCT2. (PMID:21335086)
• 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)
• Thus CpG methylation at the upstream USF-binding site functions in establishing and maintaining cell-specific transcription from the CpG-poor SVCT2 exon 1a promoter. (PMID:21770893)
• The rs1279683 single-nucleotide polymorphisms in SLC23A2 was significantly associated with lower plasma concentrations of vitamin C and with higher risk of primary open-angle glaucoma in GG subjects. (PMID:22171153)
• 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 functional expression of SVCT2 was detected in HEK293 cells.The kinetic analysis suggested that an ascorbate-dependent mechanism accounts for targeted SVCT2 expression in the developing kidney during medullary epithelial cell differentiation. (PMID:22990596)
• The novel demonstration of SVCT2-dependent mitochondrial transport of ascorbic acid. (PMID:23288661)
• confirmed the association between rs1279683 (SLC23A2) and primary open-angle glaucoma (PMID:23401652)
• 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)
• Genetic variation in the sodium-dependent vitamin C transporter 2 may have a role in acute coronary syndrome in women (PMID:23990905)
• Low SVCT2 transporter is associated with Type I diabetes. (PMID:23999113)
• Demonstrate that the expression of SVCT2 transporter is significantly down-regulated in human grade 3 osteoarthritic tissues. (PMID:24401033)
• We propose that the mitochondrial localization of SVCT2 is a property shared across cells, tissues, and species. (PMID:24594434)
• polymorphisms in SLC23A1/2 genes influenced ascorbate concentration in aqueous humor and lens nucleus. (PMID:24815519)
• ascorbic acid uptake mechanism, kinetics, and regulation by sodium dependent vitamin C transporter (SVCT2) in MDA-MB231, T47D and ZR-75-1 cells. (PMID:25102111)
• Vitamin C supplementation significantly increases skeletal muscle SVCT2 protein expression. (PMID:25242204)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc23a2	ENSDARG00000017365
mus_musculus	Slc23a2	ENSMUSG00000027340
rattus_norvegicus	Slc23a2	ENSRNOG00000021262
drosophila_melanogaster	CG6293	FBGN0037807

Paralogs (2): SLC23A1 (ENSG00000170482), SLC23A3 (ENSG00000213901)

Protein

Protein identifiers

Solute carrier family 23 member 2 — Q9UGH3 (reviewed: Q9UGH3)

Alternative names: Na(+)/L-ascorbic acid transporter 2, Nucleobase transporter-like 1 protein, Sodium-dependent vitamin C transporter 2, Yolk sac permease-like molecule 2

All UniProt accessions (3): Q9UGH3, A0A140VK48, H0Y544

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.

Subunit / interactions. Interacts with CLSTN3.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGH3-1	1	yes
Q9UGH3-2	2

RefSeq proteins (2): NP_005107, NP_976072 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006042	Xan_ur_permease	Family
IPR006043	NCS2	Family

Pfam: PF00860

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (46 total): topological domain 14, transmembrane region 12, sequence conflict 7, modified residue 6, glycosylation site 2, chain 1, intramembrane region 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGH3-F1	77.73	0.38

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 (6): 70, 75, 78, 79, 81, 649

Glycosylation sites (2): 188, 196

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 (10): response to oxidative stress (GO:0006979), cell adhesion (GO:0007155), blood circulation (GO:0008015), L-ascorbic acid transmembrane transport (GO:0015882), L-ascorbic acid metabolic process (GO:0019852), cellular response to ethanol (GO:0071361), positive regulation of dendrite extension (GO:1903861), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), transmembrane transport (GO:0055085)

GO Molecular Function (5): L-ascorbate:sodium symporter activity (GO:0008520), L-ascorbic acid transmembrane transporter activity (GO:0015229), protein binding (GO:0005515), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), basal plasma membrane (GO:0009925)

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
plasma membrane region	3
cellular process	2
transport	2
monosaccharide transmembrane transporter activity	2
carboxylic acid transmembrane transporter activity	2
cellular anatomical structure	2
response to stress	1
circulatory system process	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
response to ethanol	1
cellular response to alcohol	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
dendrite extension	1
regulation of dendrite extension	1
metal ion transport	1
organic acid:sodium symporter activity	1
carbohydrate:monoatomic cation symporter activity	1
L-ascorbic acid transmembrane transport	1
vitamin transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
basal plasma membrane	1
apical part of cell	1
basal part of cell	1

Protein interactions and networks

STRING

1516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC23A2	MATR3	P43243	839
SLC23A2	SFTPB	P07988	660
SLC23A2	SLC2A3	P11169	607
SLC23A2	SLC2A1	P11166	593
SLC23A2	TTPA	P49638	577
SLC23A2	SIL1	Q9H173	430
SLC23A2	GATA1	P15976	427
SLC23A2	SLC5A6	Q9Y289	414
SLC23A2	TET1	Q8NFU7	411
SLC23A2	SLC2A8	Q9NY64	407
SLC23A2	RGN	Q15493	401
SLC23A2	GPX4	P36969	398
SLC23A2	SLC2A12	Q8TD20	394
SLC23A2	ZZZ3	Q8IYH5	393
SLC23A2	URB1	O60287	390

IntAct

17 interactions, top by confidence:

A	B	Type	Score
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
RPL7A	SLC23A2	psi-mi:“MI:0915”(physical association)	0.400
SLC23A2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
SLC23A2	GLCCI1	psi-mi:“MI:0915”(physical association)	0.400
SLC23A2	RASGEF1A	psi-mi:“MI:0915”(physical association)	0.400
AGPAT2	SLC23A2	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC23A2	APOE	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (45): COA1 (Affinity Capture-MS), SLC23A2 (Affinity Capture-RNA), SLC23A2 (Proximity Label-MS), SLC23A2 (Proximity Label-MS), SLC23A2 (Proximity Label-MS), ERMP1 (Two-hybrid), SLC38A7 (Two-hybrid), C3orf52 (Two-hybrid), SLC41A1 (Two-hybrid), TMEM60 (Two-hybrid), NSG1 (Two-hybrid), JAGN1 (Two-hybrid), SLC23A2 (Affinity Capture-MS), SLC23A2 (Affinity Capture-MS), SLC23A2 (Proximity Label-MS)

ESM2 similar proteins: A0A2C9VBV6, B0JZG0, B3MRS1, B3NV41, B4JMC1, B4L7U0, B4MEG2, O49423, O60146, O64769, O80739, P31662, P38925, P50505, Q08469, Q10177, Q5JK32, Q5JMH0, Q5R9C2, Q652J4, Q653B6, Q67UC7, Q69L87, Q69RI8, Q6H4L9, Q6H4M2, Q6H4R6, Q6VVA6, Q6YSA9, Q75G84, Q7XLC6, Q7XPL3, Q84MS3, Q84MS4, Q84YJ9, Q8BG16, Q8BJI1, Q8LPL8, Q8VXB1, Q9EPR4

Diamond homologs: B0JZG0, O04472, P93039, Q0WPE9, Q27GI3, Q3E7D0, Q41760, Q60850, Q6PIS1, Q6SZ87, Q8GZD4, Q8RWE9, Q8VZQ5, Q94C70, Q9EPR4, Q9SHZ3, Q9UGH3, Q9UHI7, Q9WTW7, Q9WTW8, Q9Z2J0, Q3E956, P50487, P42086

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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.

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	68.5×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	9
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

6288 predictions. Top by Δscore:

Variant	Effect	Δscore
20:4859284:CGTA:C	donor_loss	1.0000
20:4859285:GTAC:G	donor_loss	1.0000
20:4859286:TACCT:T	donor_loss	1.0000
20:4859287:A:C	donor_loss	1.0000
20:4859288:C:CA	donor_loss	1.0000
20:4859382:TCC:T	acceptor_gain	1.0000
20:4859383:CC:C	acceptor_gain	1.0000
20:4859383:CCC:C	acceptor_gain	1.0000
20:4859384:CC:C	acceptor_gain	1.0000
20:4859385:C:CC	acceptor_gain	1.0000
20:4859385:CTAGA:C	acceptor_loss	1.0000
20:4862772:TCTTA:T	donor_loss	1.0000
20:4862773:CTTA:C	donor_loss	1.0000
20:4862774:TTACC:T	donor_loss	1.0000
20:4862775:TAC:T	donor_loss	1.0000
20:4862776:A:AC	donor_gain	1.0000
20:4862776:ACCA:A	donor_loss	1.0000
20:4862777:C:CC	donor_gain	1.0000
20:4862777:C:CG	donor_loss	1.0000
20:4869901:CGTA:C	donor_loss	1.0000
20:4869902:GTA:G	donor_loss	1.0000
20:4869903:TACC:T	donor_loss	1.0000
20:4869904:ACC:A	donor_loss	1.0000
20:4869905:C:CG	donor_loss	1.0000
20:4870049:CTGAA:C	acceptor_gain	1.0000
20:4870050:TGAA:T	acceptor_gain	1.0000
20:4870051:GAA:G	acceptor_gain	1.0000
20:4870052:AAC:A	acceptor_loss	1.0000
20:4870053:ACT:A	acceptor_loss	1.0000
20:4870054:C:CC	acceptor_gain	1.0000

AlphaMissense

4222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:4859303:T:A	D569V	1.000
20:4862024:G:C	N516K	1.000
20:4862024:G:T	N516K	1.000
20:4867774:G:A	T451I	1.000
20:4867794:G:C	N444K	1.000
20:4867794:G:T	N444K	1.000
20:4869953:A:C	C401W	1.000
20:4869969:C:T	G396D	1.000
20:4869975:G:A	S394F	1.000
20:4869976:A:G	S394P	1.000
20:4870001:A:C	S385R	1.000
20:4870001:A:T	S385R	1.000
20:4870003:T:G	S385R	1.000
20:4899561:C:T	G159E	1.000
20:4857059:G:C	S622R	0.999
20:4857059:G:T	S622R	0.999
20:4857061:T:G	S622R	0.999
20:4857186:C:T	G580E	0.999
20:4857187:C:G	G580R	0.999
20:4857187:C:T	G580R	0.999
20:4857188:T:A	R579S	0.999
20:4857188:T:G	R579S	0.999
20:4859303:T:G	D569A	0.999
20:4859304:C:A	D569Y	0.999
20:4859304:C:G	D569H	0.999
20:4859327:C:T	G561E	0.999
20:4859328:C:A	G561W	0.999
20:4859328:C:G	G561R	0.999
20:4859328:C:T	G561R	0.999
20:4861992:C:T	G527E	0.999

dbSNP variants (sampled 300 via entrez): RS1000023913 (20:4862593 T>C), RS1000068031 (20:5006535 C>T), RS1000082995 (20:4910595 C>T), RS1000084792 (20:4981923 G>A,C), RS1000101431 (20:4895313 G>A,T), RS1000119802 (20:5006363 C>A), RS1000125151 (20:4884750 T>A,C), RS1000126117 (20:4973565 T>C), RS1000155517 (20:4973303 T>A), RS1000203343 (20:4919761 C>T), RS1000241844 (20:4872656 G>T), RS1000252911 (20:4880351 A>G), RS1000254292 (20:4919514 C>G,T), RS1000266585 (20:4949033 C>T), RS1000266768 (20:4891317 C>T)

Disease associations

OMIM: gene MIM:603791 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST005951_151	Body mass index	6.000000e-07
GCST008163_579	Height	3.000000e-06
GCST010725_68	Malaria	4.000000e-07
GCST010725_7	Malaria	2.000000e-06
GCST010796_3063	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3064	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_3065	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-14
GCST010796_3066	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-14
GCST011816_3	Vitamin C levels	5.000000e-90
GCST012490_182	Femur bone mineral density x serum urate levels interaction	3.000000e-08
GCST012490_349	Femur bone mineral density x serum urate levels interaction	2.000000e-13
GCST90002385_347	High light scatter reticulocyte count	2.000000e-11
GCST90002386_41	High light scatter reticulocyte percentage of red cells	9.000000e-11
GCST90002387_310	Immature fraction of reticulocytes	1.000000e-09
GCST90002390_667	Mean corpuscular hemoglobin	1.000000e-17
GCST90002392_83	Mean corpuscular volume	7.000000e-20
GCST90002404_546	Red cell distribution width	4.000000e-15

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004327	electrocardiography
EFO:0600003	vitamin C measurement
EFO:0004531	urate measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3271 (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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression, increases expression	6
Valproic Acid	affects expression, decreases methylation, increases expression	6
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	3
bisphenol A	affects expression, decreases expression	2
trichostatin A	affects cotreatment, increases expression	2
arsenite	increases methylation, affects binding, decreases reaction	2
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
cobaltous chloride	decreases expression	2
nickel sulfate	decreases expression, decreases reaction	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Ascorbic Acid	decreases expression, decreases reaction, increases uptake	2
Carbamazepine	affects expression, increases expression	2
Indomethacin	increases expression, decreases reaction, increases uptake, affects cotreatment	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
aflatoxin B2	increases methylation	1
6-deoxy-6-bromoascorbic acid	affects transport	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1

ChEMBL screening assays

28 unique, capped per target: 28 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL796190	Functional	[14C]- AA uptake mediated by sodium-dependent ascorbate transporters, SVCT2 measured as Michaelis-Menten constant (Kt) at a concentration of 24 uM	Design, synthesis and activity of ascorbic acid prodrugs of nipecotic, kynurenic and diclophenamic acids, liable to increase neurotropic activity. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4J5	HCT116-SLC23A2-KO-c4	Cancer cell line	Male
CVCL_D4J6	HCT116-SLC23A2-KO-c8	Cancer cell line	Male
CVCL_E0NP	Ubigene HeLa SLC23A2 KO	Cancer cell line	Female
CVCL_TM01	HAP1 SLC23A2 (-) 1	Cancer cell line	Male
CVCL_XS98	HAP1 SLC23A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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