SLC23A3

Summary

SLC23A3 (solute carrier family 23 member 3, HGNC:20601) is a protein-coding gene on chromosome 2q35, encoding Solute carrier family 23 member 3 (Q6PIS1). Acts as a sodium-dependent hypoxanthine transporter.

Predicted to enable transmembrane transporter activity. Involved in hypoxanthine transport. Predicted to be located in membrane.

Source: NCBI Gene 151295 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_001144889

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20601
Approved symbol	SLC23A3
Name	solute carrier family 23 member 3
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	SVCT3, FLJ31168, Yspl1
Ensembl gene	ENSG00000213901
Ensembl biotype	protein_coding
OMIM	620339
Entrez	151295

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000295738, ENST00000409370, ENST00000409878, ENST00000414999, ENST00000421779, ENST00000430764, ENST00000455516, ENST00000461812, ENST00000465580, ENST00000497918, ENST00000858810, ENST00000858811

RefSeq mRNA: 3 — MANE Select: NM_001144889 NM_001144889, NM_001144890, NM_144712

CCDS: CCDS42819, CCDS46517, CCDS46518

Canonical transcript exons

ENST00000409878 — 12 exons

Exon	Start	End
ENSE00001581895	219165169	219165422
ENSE00001828902	219169823	219170029
ENSE00003465693	219169521	219169678
ENSE00003489814	219169309	219169406
ENSE00003513185	219162299	219162394
ENSE00003536644	219167930	219168044
ENSE00003537893	219163388	219163555
ENSE00003539620	219169029	219169102
ENSE00003583612	219164233	219164338
ENSE00003635030	219168195	219168318
ENSE00003789532	219168652	219168833
ENSE00003899509	219161465	219162204

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 98.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1098 / max 63.2224, expressed in 14 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34023	0.0616	11
34024	0.0482	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.74	gold quality
ileal mucosa	UBERON:0000331	98.05	gold quality
mucosa of transverse colon	UBERON:0004991	89.72	gold quality
tibialis anterior	UBERON:0001385	86.90	silver quality
adult mammalian kidney	UBERON:0000082	86.58	gold quality
cortex of kidney	UBERON:0001225	86.21	gold quality
kidney	UBERON:0002113	85.53	gold quality
pancreatic ductal cell	CL:0002079	84.79	silver quality
lower esophagus mucosa	UBERON:0035834	83.57	gold quality
renal medulla	UBERON:0000362	82.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.55	gold quality
left ventricle myocardium	UBERON:0006566	81.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.37	gold quality
small intestine	UBERON:0002108	80.85	gold quality
metanephros cortex	UBERON:0010533	80.41	gold quality
jejunal mucosa	UBERON:0000399	80.34	gold quality
duodenum	UBERON:0002114	80.26	gold quality
adult organism	UBERON:0007023	79.63	gold quality
upper arm skin	UBERON:0004263	76.99	gold quality
transverse colon	UBERON:0001157	76.08	gold quality
metanephros	UBERON:0000081	75.83	gold quality
right coronary artery	UBERON:0001625	74.60	gold quality
germinal epithelium of ovary	UBERON:0001304	74.56	gold quality
epithelium of nasopharynx	UBERON:0001951	74.46	gold quality
jejunum	UBERON:0002115	74.44	gold quality
right lobe of liver	UBERON:0001114	73.96	gold quality
right lobe of thyroid gland	UBERON:0001119	73.65	gold quality
deltoid	UBERON:0001476	73.63	silver quality
gingival epithelium	UBERON:0001949	73.44	gold quality
descending thoracic aorta	UBERON:0002345	73.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	7.72
E-ANND-3	no	1.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting SLC23A3, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-1256	95.44	66.33	784
HSA-MIR-6753-5P	94.70	64.08	470
HSA-MIR-1296-5P	93.94	67.71	305
HSA-MIR-1537-3P	90.51	63.57	105

Literature-anchored findings (GeneRIF, showing 2)

• In the course of differentiation, the most pronounced changes in the expression levels were observed for the mRNAs that encode SLC30A10 and SLC23A3 transporters. Their increase correlated with an increase in the apical membrane area, indicating that SLC30A10 and SLC23A3 mRNA levels assessed by qRT-PCR may be employed as cell differentiation biomarkers in Caco-2 models. (PMID:30113032)
• SLC23A3 is a renal hypoxanthine transporter. (PMID:35094660)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc23a3	ENSDARG00000088891
mus_musculus	Slc23a3	ENSMUSG00000026205
rattus_norvegicus	Slc23a3	ENSRNOG00000018266
caenorhabditis_elegans		WBGENE00008252
caenorhabditis_elegans		WBGENE00011593
caenorhabditis_elegans		WBGENE00011595
caenorhabditis_elegans		WBGENE00011596
caenorhabditis_elegans		WBGENE00020004
caenorhabditis_elegans		WBGENE00021994

Paralogs (2): SLC23A2 (ENSG00000089057), SLC23A1 (ENSG00000170482)

Protein

Protein identifiers

Solute carrier family 23 member 3 — Q6PIS1 (reviewed: Q6PIS1)

Alternative names: HPC E2-binding protein 3, Na(+)/L-ascorbic acid transporter 3, Sodium-dependent vitamin C transporter 3

All UniProt accessions (4): A0A0A0MSG3, C9JQ03, H7C2A2, Q6PIS1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a sodium-dependent hypoxanthine transporter. May show xanthine-hypoxanthine exchange activity.

Subcellular location. Membrane.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6PIS1-1	1	yes
Q6PIS1-2	2
Q6PIS1-5	3

RefSeq proteins (3): NP_001138361, NP_001138362, NP_653313 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006043	NCS2	Family

Pfam: PF00860

Catalyzed reactions (Rhea), 1 shown:

• hypoxanthine(out) + Na(+)(out) = hypoxanthine(in) + Na(+)(in) (RHEA:76279)

UniProt features (35 total): topological domain 13, transmembrane region 12, compositionally biased region 3, region of interest 2, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PIS1-F1	75.79	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): HNF4_DR1_Q3, RYTAAWNNNTGAY_UNKNOWN, HNF4_01, PPAR_DR1_Q2, PPARA_01, GOBP_TRANSMEMBRANE_TRANSPORT, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, WGTTNNNNNAAA_UNKNOWN, COUP_DR1_Q6, RASHI_RESPONSE_TO_IONIZING_RADIATION_1, GOMF_TRANSPORTER_ACTIVITY, MIKKELSEN_IPS_LCP_WITH_H3K27ME3, GOBP_NUCLEOBASE_TRANSPORT, SUPT16H_TARGET_GENES, MIR4731_5P

GO Biological Process (2): hypoxanthine transport (GO:0035344), transmembrane transport (GO:0055085)

GO Molecular Function (1): transmembrane transporter activity (GO:0022857)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine nucleobase transport	1
transport	1
cellular process	1
transporter activity	1
transmembrane transport	1
cellular anatomical structure	1

Protein interactions and networks

STRING

498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC23A3	SNRPF	P62306	505
SLC23A3	RER1	O15258	478
SLC23A3	CHPT1	Q8WUD6	470
SLC23A3	SLC16A9	Q7RTY1	470
SLC23A3	BCAS3	Q9H6U6	462
SLC23A3	GSTA5	Q7RTV2	420
SLC23A3	SLC17A4	Q9Y2C5	419
SLC23A3	FDXACB1	Q9BRP7	404
SLC23A3	RGS14	O43566	400
SLC23A3	SLC5A9	Q2M3M2	380
SLC23A3	MFSD11	O43934	377
SLC23A3	TEX22	C9J3V5	370
SLC23A3	CNPPD1	Q9BV87	368
SLC23A3	SLC7A4	O43246	357
SLC23A3	LRRC1	Q9BTT6	349

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SLC23A3	IGF1R	psi-mi:“MI:0915”(physical association)	0.400
SLC23A3	PRODH	psi-mi:“MI:0915”(physical association)	0.400
SLC23A3	PGRMC2	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): PRODH (Affinity Capture-MS), PRODH (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), SSR1 (Affinity Capture-MS), SSR4 (Affinity Capture-MS), SLC23A3 (Affinity Capture-Western)

ESM2 similar proteins: A6NGC4, A6NKX4, A6NM10, F1NZP5, O96011, P0C242, P27544, P27545, Q0VCY6, Q2TBI8, Q3SYU3, Q4V8E5, Q5F2F2, Q5JZQ7, Q5RFI0, Q5U2T1, Q5U419, Q6AYM9, Q6GQT6, Q6PIS1, Q6TCG5, Q6UXD7, Q6UXT9, Q71RH2, Q7TNV1, Q7Z403, Q80ZE4, Q863Y8, Q86WI3, Q8BMT9, Q8CHK3, Q8IU68, Q8IXF9, Q8N9H8, Q8TBR7, Q8VC26, Q8WUG5, Q96N66, Q99640, Q99JT6

Diamond homologs: B0JZG0, O04472, P93039, Q0WPE9, Q27GI3, Q3E7D0, Q41760, Q60850, Q6PIS1, Q6SZ87, Q8GZD4, Q8RWE9, Q8VZQ5, Q94C70, Q9EPR4, Q9SHZ3, Q9UGH3, Q9UHI7, Q9WTW7, Q9WTW8, Q9Z2J0, A0A2A5JY22, O32139, O32140, P0AGM9, P0AGN0, P0AGN1, P0AGN2, P42086, P50487, P67444, P67445, P67446, Q46821, P45117, Q9CPL9, Q3E956

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2167 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219163383:CCTA:C	donor_loss	1.0000
2:219163384:CTACC:C	donor_loss	1.0000
2:219163385:TAC:T	donor_loss	1.0000
2:219163386:A:AT	donor_loss	1.0000
2:219163514:C:CT	acceptor_gain	1.0000
2:219163515:A:T	acceptor_gain	1.0000
2:219162104:CA:C	donor_gain	0.9900
2:219162121:C:CA	donor_gain	0.9900
2:219163381:CACCT:C	donor_loss	0.9900
2:219163382:ACCTA:A	donor_loss	0.9900
2:219163385:TACC:T	donor_loss	0.9900
2:219163514:C:T	acceptor_gain	0.9900
2:219163517:C:CT	acceptor_gain	0.9900
2:219163563:A:C	acceptor_gain	0.9900
2:219163386:A:AC	donor_gain	0.9800
2:219163387:C:CC	donor_gain	0.9800
2:219163411:T:TA	donor_gain	0.9800
2:219163556:C:CA	acceptor_loss	0.9800
2:219163557:T:A	acceptor_loss	0.9800
2:219163563:A:AC	acceptor_gain	0.9800
2:219165418:CTCAC:C	acceptor_gain	0.9800
2:219165420:CACCT:C	acceptor_loss	0.9800
2:219165421:ACC:A	acceptor_loss	0.9800
2:219165423:C:CA	acceptor_loss	0.9800
2:219165423:C:T	acceptor_loss	0.9800
2:219165424:T:A	acceptor_loss	0.9800
2:219168695:C:A	donor_gain	0.9800
2:219161957:C:A	donor_gain	0.9700
2:219162292:AACTT:A	donor_loss	0.9700
2:219162293:ACTT:A	donor_loss	0.9700

AlphaMissense

3857 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219163470:A:C	N453K	0.973
2:219163470:A:T	N453K	0.973
2:219169373:G:C	F118L	0.964
2:219169373:G:T	F118L	0.964
2:219169375:A:G	F118L	0.964
2:219169571:G:C	S90R	0.962
2:219169571:G:T	S90R	0.962
2:219169573:T:G	S90R	0.962
2:219165377:C:T	G320D	0.956
2:219165202:G:C	S378R	0.950
2:219165202:G:T	S378R	0.950
2:219165204:T:G	S378R	0.950
2:219165378:C:G	G320R	0.946
2:219165247:A:C	S363R	0.940
2:219165247:A:T	S363R	0.940
2:219165249:T:G	S363R	0.940
2:219168808:C:T	G173E	0.938
2:219162313:T:A	E508V	0.936
2:219169523:G:C	S106R	0.936
2:219169523:G:T	S106R	0.936
2:219169525:T:G	S106R	0.936
2:219169557:C:T	G95D	0.932
2:219163513:C:T	G439E	0.917
2:219165223:G:C	S371R	0.917
2:219165223:G:T	S371R	0.917
2:219165225:T:G	S371R	0.917
2:219168809:C:G	G173R	0.917
2:219168809:C:T	G173R	0.917
2:219163443:G:C	F462L	0.915
2:219163443:G:T	F462L	0.915

dbSNP variants (sampled 300 via entrez): RS1000036236 (2:219161146 C>T), RS1000053654 (2:219162936 A>G,T), RS1000653064 (2:219164177 C>G,T), RS1001454482 (2:219169581 A>G), RS1001567573 (2:219170039 G>A), RS1001784899 (2:219171194 T>C), RS1002056794 (2:219165544 C>G,T), RS1002111016 (2:219162708 A>G), RS1002415404 (2:219164047 G>C), RS1002655110 (2:219167268 TTAAA>T,TTAAATAAA), RS1003691376 (2:219165453 C>T), RS1003782567 (2:219162791 G>A), RS1003835007 (2:219162530 C>G), RS1004054723 (2:219167730 A>G), RS1004130531 (2:219165798 C>G,T)

Disease associations

OMIM: gene MIM:620339 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000175_19	Height	1.000000e-06
GCST002702_34	Height	1.000000e-11
GCST008163_280	Height	1.000000e-06
GCST011816_2	Vitamin C levels	2.000000e-30
GCST012226_195	Waist circumference adjusted for body mass index	5.000000e-08
GCST012226_197	Waist circumference adjusted for body mass index	2.000000e-10
GCST90002392_175	Mean corpuscular volume	2.000000e-09
GCST90020028_715	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0600003	vitamin C measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Arbutin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression, affects cotreatment	1
Hydralazine	affects cotreatment, increases expression	1
Rifampin	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
S-Nitrosoglutathione	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4EQ	1321N1-SLC23A3-KO-c6	Cancer cell line	Male
CVCL_D4ER	1321N1-SLC23A3-KO-c7	Cancer cell line	Male

Clinical trials (associated diseases)

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