SLC13A4

Summary

SLC13A4 (solute carrier family 13 member 4, HGNC:15827) is a protein-coding gene on chromosome 7q33, encoding Solute carrier family 13 member 4 (Q9UKG4). Sodium:sulfate symporter that mediates sulfate reabsorption in the high endothelial venules (HEV).

Enables sodium:sulfate symporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 26266 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001318192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15827
Approved symbol	SLC13A4
Name	solute carrier family 13 member 4
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	SUT-1, SUT1
Ensembl gene	ENSG00000164707
Ensembl biotype	protein_coding
OMIM	604309
Entrez	26266

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000354042, ENST00000378428, ENST00000422620, ENST00000471405, ENST00000478310, ENST00000480376, ENST00000491630, ENST00000682651, ENST00000713945, ENST00000713946

RefSeq mRNA: 2 — MANE Select: NM_001318192 NM_001318192, NM_012450

CCDS: CCDS5840, CCDS94210

Canonical transcript exons

ENST00000682651 — 16 exons

Exon	Start	End
ENSE00001198769	135727398	135728186
ENSE00003381826	135706128	135706300
ENSE00003403513	135705596	135705650
ENSE00003468058	135691548	135691645
ENSE00003483510	135694137	135694238
ENSE00003484468	135692323	135692424
ENSE00003533904	135691201	135691325
ENSE00003561500	135685522	135685683
ENSE00003568609	135701680	135701760
ENSE00003587813	135699364	135699548
ENSE00003632854	135695368	135695487
ENSE00003633589	135708114	135708250
ENSE00003667610	135684124	135684261
ENSE00003710560	135721395	135721523
ENSE00003920029	135681231	135681700
ENSE00003920537	135702845	135702884

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 97.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9110 / max 476.9988, expressed in 181 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86369	1.8147	181
86368	0.0963	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	97.02	gold quality
placenta	UBERON:0001987	92.26	gold quality
cerebellar vermis	UBERON:0004720	88.67	gold quality
buccal mucosa cell	CL:0002336	86.69	silver quality
trigeminal ganglion	UBERON:0001675	86.66	gold quality
lower esophagus mucosa	UBERON:0035834	83.37	gold quality
secondary oocyte	CL:0000655	79.31	gold quality
cranial nerve II	UBERON:0000941	77.32	gold quality
esophagus mucosa	UBERON:0002469	76.54	gold quality
left testis	UBERON:0004533	75.09	gold quality
corpus callosum	UBERON:0002336	74.61	gold quality
right testis	UBERON:0004534	74.47	gold quality
right uterine tube	UBERON:0001302	73.94	gold quality
pigmented layer of retina	UBERON:0001782	73.67	gold quality
oocyte	CL:0000023	73.39	gold quality
ascending aorta	UBERON:0001496	73.30	gold quality
stromal cell of endometrium	CL:0002255	72.99	gold quality
thoracic aorta	UBERON:0001515	72.87	gold quality
testis	UBERON:0000473	72.71	gold quality
right coronary artery	UBERON:0001625	72.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.94	gold quality
olfactory bulb	UBERON:0002264	71.76	gold quality
bronchial epithelial cell	CL:0002328	71.72	gold quality
vagina	UBERON:0000996	71.69	gold quality
apex of heart	UBERON:0002098	71.61	gold quality
epithelium of bronchus	UBERON:0002031	71.55	gold quality
esophagus	UBERON:0001043	71.19	gold quality
bronchus	UBERON:0002185	71.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.09	gold quality
descending thoracic aorta	UBERON:0002345	71.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF7, NFYA, NHLH1, SP1, ZIC2

miRNA regulators (miRDB)

19 targeting SLC13A4, 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-4775	99.98	75.00	6394
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-1287-5P	96.80	65.30	743

Literature-anchored findings (GeneRIF, showing 5)

• Here, we characterized the functional properties of the human Na(+)-sulfate cotransporter (hNaS2), determined its tissue distribution, and identified its gene (SLC13A4) structure. (PMID:15607730)
• SLC13A4 and SLC26A2 were the most abundant sulfate transporter mRNAs, which localized to syncytiotrophoblast and cytotrophoblast cells, respectively. (PMID:23453247)
• To investigate the regulation of SLC13A4 gene expression, we analysed the transcriptional activity of the SLC13A4 5’-flanking region in the JEG-3 placental cell line using luciferase reporter assays. (PMID:23485456)
• Study found that despite differential expression of the two SLC13A4 transcripts, no detectable functional difference in the cellular sorting or sulfate transporting was found. However, some variants can influence both mechanism in specific cell membranes. This is like to have clinical implications based on the consequences of impaired sulfate transport during pregnancy in rodent models. (PMID:28385533)
• SLC13A4 Might Serve as a Prognostic Biomarker and be Correlated with Immune Infiltration into Head and Neck Squamous Cell Carcinoma. (PMID:34840533)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc13a4	ENSDARG00000059053
mus_musculus	Slc13a4	ENSMUSG00000029843
rattus_norvegicus	Slc13a4	ENSRNOG00000011184
drosophila_melanogaster	CG7309	FBGN0032314
drosophila_melanogaster	Indy	FBGN0036816
drosophila_melanogaster	CG33934	FBGN0064119
drosophila_melanogaster	Indy-2	FBGN0260466
caenorhabditis_elegans		WBGENE00003517
caenorhabditis_elegans		WBGENE00003518
caenorhabditis_elegans		WBGENE00003519
caenorhabditis_elegans		WBGENE00007138

Paralogs (5): SLC13A2 (ENSG00000007216), SLC13A1 (ENSG00000081800), OCA2 (ENSG00000104044), SLC13A5 (ENSG00000141485), SLC13A3 (ENSG00000158296)

Protein

Protein identifiers

Solute carrier family 13 member 4 — Q9UKG4 (reviewed: Q9UKG4)

Alternative names: Na(+)/sulfate cotransporter SUT-1, NaS2

All UniProt accessions (4): A0A804HKQ4, A0AAQ5BH30, A0AAQ5BH36, Q9UKG4

UniProt curated annotations — full annotation on UniProt →

Function. Sodium:sulfate symporter that mediates sulfate reabsorption in the high endothelial venules (HEV).

Subcellular location. Membrane.

Tissue specificity. Highly expressed in placenta and testis with intermediate levels in brain and lower levels in heart, thymus and liver.

Activity regulation. Transport is inhibited by thiosulfate, phosphate, molybdate, selenate and tungstate. Not inhibited by oxalate, citrate, succinate, phenol red or 4,4’-diisothiocyanostilbene-2,2’-disulfonic acid (DIDS).

Similarity. Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.

RefSeq proteins (2): NP_001305121, NP_036582 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001898	SLC13A/DASS	Family

Pfam: PF00939

Catalyzed reactions (Rhea), 1 shown:

• sulfate(out) + 3 Na(+)(out) = sulfate(in) + 3 Na(+)(in) (RHEA:71951)

UniProt features (19 total): transmembrane region 12, sequence conflict 3, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKG4-F1	77.35	0.40

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-433137	Sodium-coupled sulphate, di- and tri-carboxylate transporters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 64 (showing top): GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, AACTTT_UNKNOWN, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, WGTTNNNNNAAA_UNKNOWN, GOMF_SULFUR_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SOLUTE_MONOATOMIC_CATION_SYMPORTER_ACTIVITY, GOMF_SECONDARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SYMPORTER_ACTIVITY

GO Biological Process (5): transmembrane transport (GO:0055085), sulfate transmembrane transport (GO:1902358), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), sodium ion transmembrane transport (GO:0035725)

GO Molecular Function (5): sodium:sulfate symporter activity (GO:0015382), transmembrane transporter activity (GO:0022857), protein binding (GO:0005515), symporter activity (GO:0015293), solute:sodium symporter activity (GO:0015370)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
transmembrane transport	2
cellular process	1
inorganic anion transport	1
sulfur compound transport	1
metal ion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
secondary active sulfate transmembrane transporter activity	1
solute:sodium symporter activity	1
transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
solute:monoatomic cation symporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC13A4	SLC26A2	P50443	879
SLC13A4	PSMD9	O00233	864
SLC13A4	PAAF1	Q9BRP4	848
SLC13A4	SLC26A3	P40879	753
SLC13A4	PSMC6	P49719	711
SLC13A4	PSMC4	P43686	674
SLC13A4	SLC26A4	O43511	647
SLC13A4	PSMC3	P17980	582
SLC13A4	POMP	Q9Y244	514
SLC13A4	ADRM1	Q16186	505
SLC13A4	PSMG4	Q5JS54	471
SLC13A4	PSMG3	Q9BT73	445
SLC13A4	NPM1	P06748	445
SLC13A4	PSMD4	P55036	435
SLC13A4	SLC5A11	Q8WWX8	433

IntAct

83 interactions, top by confidence:

A	B	Type	Score
SLC13A4	GJA5	psi-mi:“MI:0915”(physical association)	0.560
OPRD1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
GPR61	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC38A1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
ACKR2	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
TMEM60	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
DEFB108B	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
CBLIF	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
ERMP1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
CDS1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
GPR152	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
CD79A	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
TMEM147	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
IER3	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC35A4	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
DERL3	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
EOGT	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
CERS4	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
GJA5	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC13A4	POLR3A	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): SLC13A4 (Proximity Label-MS), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid), SLC13A4 (Two-hybrid)

ESM2 similar proteins: A0A494BA31, G3C7W6, O08812, O43246, O97704, P02730, P04919, P15575, P23562, P26430, P31639, P45380, P53792, P58735, P70423, P92946, Q06495, Q06496, Q28615, Q28728, Q58DD2, Q5EBI0, Q60825, Q63008, Q7LBE3, Q80SU6, Q80ZD3, Q86U10, Q86WA9, Q8BLQ7, Q8BU91, Q8CIW6, Q8K4R8, Q8K4V2, Q8N130, Q8NG04, Q8R2Z3, Q923I7, Q92911, Q96Q91

Diamond homologs: O59712, P25360, P32739, P46556, P70545, P72958, Q07782, Q13183, Q21339, Q28615, Q2FFH9, Q2FWY4, Q2YU56, Q49YW0, Q5HEK4, Q67BT3, Q6G816, Q6GFE0, Q7A4P8, Q86YT5, Q8CJ44, Q8LG88, Q8NVS5, Q8WWT9, Q91Y63, Q93655, Q99SX1, Q9BZW2, Q9ES88, Q9JHI4, Q9UKG4, Q9VDQ0, Q9VVT2, Q9Z0Z5, P27514, P0AFU2, P0AFU3, P86282

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2278 predictions. Top by Δscore:

Variant	Effect	Δscore
7:135684117:AAC:A	donor_loss	1.0000
7:135684118:ACT:A	donor_loss	1.0000
7:135684119:CT:C	donor_loss	1.0000
7:135684120:TCA:T	donor_loss	1.0000
7:135684121:CACC:C	donor_loss	1.0000
7:135684122:ACCAT:A	donor_loss	1.0000
7:135684195:C:CC	acceptor_gain	1.0000
7:135685513:ATTAC:A	donor_loss	1.0000
7:135685514:TTACT:T	donor_loss	1.0000
7:135685516:ACTC:A	donor_loss	1.0000
7:135685518:T:TA	donor_loss	1.0000
7:135685519:C:CC	donor_loss	1.0000
7:135685520:ACCAG:A	donor_loss	1.0000
7:135685521:CCAGG:C	donor_gain	1.0000
7:135691331:T:TC	acceptor_gain	1.0000
7:135691536:C:A	donor_gain	1.0000
7:135692320:TACTT:T	donor_loss	1.0000
7:135692321:A:AC	donor_gain	1.0000
7:135692322:C:CA	donor_gain	1.0000
7:135692322:CT:C	donor_gain	1.0000
7:135692322:CTT:C	donor_gain	1.0000
7:135692322:CTTT:C	donor_gain	1.0000
7:135692322:CTTTT:C	donor_gain	1.0000
7:135692420:GGTAG:G	acceptor_gain	1.0000
7:135692421:GTAG:G	acceptor_gain	1.0000
7:135692422:TAG:T	acceptor_gain	1.0000
7:135692423:AG:A	acceptor_gain	1.0000
7:135692424:GCTAT:G	acceptor_gain	1.0000
7:135692425:C:CC	acceptor_gain	1.0000
7:135692427:A:AC	acceptor_gain	1.0000

AlphaMissense

4112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:135691254:A:G	W464R	1.000
7:135691254:A:T	W464R	1.000
7:135692342:A:G	W401R	1.000
7:135692342:A:T	W401R	1.000
7:135699403:C:T	G286D	1.000
7:135699404:C:G	G286R	1.000
7:135699424:C:T	G279D	1.000
7:135708150:A:G	L110P	1.000
7:135708159:C:G	R107P	1.000
7:135708160:G:T	R107S	1.000
7:135708208:C:G	G91R	1.000
7:135708208:C:T	G91R	1.000
7:135681670:C:G	G592R	0.999
7:135681670:C:T	G592R	0.999
7:135681690:C:T	G585D	0.999
7:135681691:C:G	G585R	0.999
7:135684158:A:T	V570D	0.999
7:135684165:C:G	A568P	0.999
7:135684166:A:C	N567K	0.999
7:135684166:A:T	N567K	0.999
7:135684175:A:C	N564K	0.999
7:135684175:A:T	N564K	0.999
7:135684180:C:G	G563R	0.999
7:135684185:G:T	P561H	0.999
7:135685564:G:C	N521K	0.999
7:135685564:G:T	N521K	0.999
7:135685567:G:C	S520R	0.999
7:135685567:G:T	S520R	0.999
7:135685569:T:G	S520R	0.999
7:135691208:C:T	G479D	0.999

dbSNP variants (sampled 300 via entrez): RS1000093884 (7:135728099 G>C,T), RS1000250279 (7:135703719 CAGAG>C,CAG), RS1000304512 (7:135713802 C>A), RS1000357611 (7:135710274 A>C,T), RS1000399103 (7:135721697 A>C,G), RS1000544903 (7:135706029 G>C,T), RS1000561121 (7:135698978 T>G), RS1000613329 (7:135707295 G>A), RS1000641664 (7:135712335 A>G), RS1000714901 (7:135712036 C>G), RS1000825868 (7:135717850 G>T), RS1000830955 (7:135711286 G>T), RS1000887613 (7:135692688 A>T), RS1000897448 (7:135724445 C>T), RS1001096309 (7:135711530 G>A)

Disease associations

OMIM: gene MIM:604309 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004860_4	Alcoholic chronic pancreatitis	6.000000e-06
GCST006479_1	Diverticular disease	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

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 — SLC13 family of sodium-dependent sulphate/carboxylate transporters

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
exemestane	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
bisphenol S	decreases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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