SLC13A1

Summary

SLC13A1 (solute carrier family 13 member 1, HGNC:10916) is a protein-coding gene on chromosome 7q31.32, encoding Solute carrier family 13 member 1 (Q9BZW2). Sodium:sulfate symporter that mediates sulfate reabsorption in the kidney and small intestine.

The protein encoded by this gene is an apical membrane Na(+)-sulfate cotransporter involved in sulfate homeostasis in the kidney. Defects in this gene lead to many pathophysiologic problems.

Source: NCBI Gene 6561 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sulfation-related bone disorder (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_022444

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10916
Approved symbol	SLC13A1
Name	solute carrier family 13 member 1
Location	7q31.32
Locus type	gene with protein product
Status	Approved
Aliases	NaSi-1, NAS1
Ensembl gene	ENSG00000081800
Ensembl biotype	protein_coding
OMIM	606193
Entrez	6561

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

ENST00000194130, ENST00000427975, ENST00000439260, ENST00000539873, ENST00000907906, ENST00000954470, ENST00000954471

RefSeq mRNA: 2 — MANE Select: NM_022444 NM_001324400, NM_022444

CCDS: CCDS5786

Canonical transcript exons

ENST00000194130 — 15 exons

Exon	Start	End
ENSE00001011347	123113531	123115655
ENSE00001950179	123199848	123199969
ENSE00003494544	123168374	123168422
ENSE00003511005	123128845	123128946
ENSE00003531878	123147159	123147310
ENSE00003554571	123171768	123171904
ENSE00003579742	123134410	123134529
ENSE00003626368	123168504	123168561
ENSE00003642076	123125569	123125675
ENSE00003652786	123180973	123181101
ENSE00003661681	123117471	123117608
ENSE00003665717	123119081	123119242
ENSE00003668621	123129383	123129481
ENSE00003681356	123123126	123123235
ENSE00003692555	123169148	123169335

Expression profiles

Bgee: expression breadth broad, 34 present calls, max score 92.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1369 / max 118.1503, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85962	0.1369	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	92.78	gold quality
kidney epithelium	UBERON:0004819	91.47	gold quality
renal glomerulus	UBERON:0000074	88.19	gold quality
metanephric glomerulus	UBERON:0004736	87.49	gold quality
adult mammalian kidney	UBERON:0000082	85.33	gold quality
kidney	UBERON:0002113	84.23	gold quality
buccal mucosa cell	CL:0002336	81.96	silver quality
gall bladder	UBERON:0002110	78.93	gold quality
cortex of kidney	UBERON:0001225	78.78	gold quality
metanephros	UBERON:0000081	74.22	gold quality
ileal mucosa	UBERON:0000331	73.23	gold quality
ileum	UBERON:0002116	73.17	silver quality
renal medulla	UBERON:0000362	72.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.77	gold quality
small intestine	UBERON:0002108	64.48	gold quality
metanephros cortex	UBERON:0010533	61.49	gold quality
adult organism	UBERON:0007023	60.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.54	gold quality
decidua	UBERON:0002450	56.55	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
mucosa of transverse colon	UBERON:0004991	50.57	gold quality
cranial nerve II	UBERON:0000941	50.30	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
quadriceps femoris	UBERON:0001377	48.85	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	477.28
E-CURD-119	yes	61.42
E-ANND-3	yes	9.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting SLC13A1, 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-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4753-3P	99.90	71.03	3786

Literature-anchored findings (GeneRIF, showing 8)

• Serines 260 and 288 are involved in sulfate transport by hNaSi-1. (PMID:12857732)
• Amino acid residue Asn591, located in the carboxyl (COOH) terminus of NaSi-1, is used as the glycosylation site and is critical for transport activity in NaSi-1. (PMID:12867358)
• Consistent with sulfate’s role in xenobiotic detoxification and protection against acetaminophen-induced hepatotoxicity, SLC13A1 nonsense SNV carriers had higher aminotransferase levels compared to noncarriers. (PMID:27412988)
• Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology. (PMID:35110524)
• Biallelic variants in the SLC13A1 sulfate transporter gene cause hyposulfatemia with a mild spondylo-epi-metaphyseal dysplasia. (PMID:36175384)
• Serum sulfate level and Slc13a1 mRNA expression remain unaltered in a mouse model of moderate vitamin D deficiency. (PMID:36566486)
• Rare variant analyses in large-scale cohorts identified SLC13A1 associated with chronic pain. (PMID:36943258)
• Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism. (PMID:38552027)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc13a1	ENSDARG00000045638
mus_musculus	Slc13a1	ENSMUSG00000029700
rattus_norvegicus	Slc13a1	ENSRNOG00000008121
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), OCA2 (ENSG00000104044), SLC13A5 (ENSG00000141485), SLC13A3 (ENSG00000158296), SLC13A4 (ENSG00000164707)

Protein

Protein identifiers

Solute carrier family 13 member 1 — Q9BZW2 (reviewed: Q9BZW2)

Alternative names: Renal sodium/sulfate cotransporter

All UniProt accessions (5): Q9BZW2, A4D0X1, F5GYP1, F8WEH1, F8WEM4

UniProt curated annotations — full annotation on UniProt →

Function. Sodium:sulfate symporter that mediates sulfate reabsorption in the kidney and small intestine. Can also mediate the transport of selenate and thiosulfate.

Subcellular location. Apical cell membrane.

Tissue specificity. Highly expressed in kidney; not detectable in the other tissues tested.

Activity regulation. Inhibited by thiosulfate, selenate, molybdate, tungstate, citrate and succinate.

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

RefSeq proteins (2): NP_001311329, NP_071889* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001898	SLC13A/DASS	Family
IPR031312	Na/sul_symport_CS	Conserved_site

Pfam: PF00939

Catalyzed reactions (Rhea), 3 shown:

• sulfate(out) + 3 Na(+)(out) = sulfate(in) + 3 Na(+)(in) (RHEA:71951)
• selenate(out) + 3 Na(+)(out) = selenate(in) + 3 Na(+)(in) (RHEA:72079)
• thiosulfate(out) + 3 Na(+)(out) = thiosulfate(in) + 3 Na(+)(in) (RHEA:72323)

UniProt features (27 total): transmembrane region 13, sequence variant 9, glycosylation site 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8Y5W	ELECTRON MICROSCOPY	2.73
8W6O	ELECTRON MICROSCOPY	2.9
8W6T	ELECTRON MICROSCOPY	3
8Y5U	ELECTRON MICROSCOPY	3.04
8W6H	ELECTRON MICROSCOPY	3.1
8W6N	ELECTRON MICROSCOPY	3.2
8Y5X	ELECTRON MICROSCOPY	3.25
8Y5Y	ELECTRON MICROSCOPY	3.3
8Y5Z	ELECTRON MICROSCOPY	3.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZW2-F1	81.91	0.48

Functional residue map

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

Glycosylation sites (3): 174, 207, 591

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: 110 (showing top): GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_SULFUR_COMPOUND_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, DBP_Q6, SOX5_01, GOBP_TRANSMEMBRANE_TRANSPORT, PITX2_Q2, GOBP_SODIUM_ION_TRANSPORT, EVI1_04, TUOMISTO_TUMOR_SUPPRESSION_BY_COL13A1_DN, GOCC_APICAL_PART_OF_CELL, TAATTA_CHX10_01

GO Biological Process (6): sodium ion transport (GO:0006814), sulfate transmembrane transport (GO:1902358), monoatomic ion transport (GO:0006811), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (6): monoatomic anion:sodium symporter activity (GO:0015373), sodium:sulfate symporter activity (GO:0015382), secondary active sulfate transmembrane transporter activity (GO:0008271), symporter activity (GO:0015293), solute:sodium symporter activity (GO:0015370), transmembrane transporter activity (GO:0022857)

GO Cellular Component (3): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), 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
transmembrane transport	2
transport	2
solute:sodium symporter activity	2
secondary active transmembrane transporter activity	2
metal ion transport	1
inorganic anion transport	1
sulfur compound transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
cellular process	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
monoatomic anion:monoatomic cation symporter activity	1
secondary active sulfate transmembrane transporter activity	1
sulfate transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
solute:monoatomic cation symporter activity	1
transporter activity	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC13A1	SLC26A2	P50443	903
SLC13A1	SLC26A3	P40879	816
SLC13A1	PSMD2	Q13200	761
SLC13A1	SLC26A1	Q9H2B4	746
SLC13A1	SLC26A4	O43511	628
SLC13A1	SLC3A1	Q07837	527
SLC13A1	ASB15	Q8WXK1	491
SLC13A1	SLC26A6	Q9BXS9	442
SLC13A1	PSMD9	O00233	427
SLC13A1	PSMC6	P49719	424
SLC13A1	SLC28A2	O43868	410
SLC13A1	SLC26A7	Q8TE54	409
SLC13A1	SLC41A1	Q8IVJ1	394
SLC13A1	ABCC2	Q92887	391
SLC13A1	IQCF2	Q8IXL9	390

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC13A1	ACTBL2	psi-mi:“MI:0915”(physical association)	0.400
SLC13A1	UBXN8	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): FTL (PCA), OGDHL (PCA), CD59 (PCA), SERPINA1 (PCA), COQ9 (PCA), SDHD (PCA), PDZK1 (PCA), ACTR10 (PCA), MKRN1 (PCA), ACOT2 (PCA), HSPA1A (PCA), SEC61A1 (PCA), SLC9A3R1 (PCA), RHOA (PCA), TP53I11 (PCA)

ESM2 similar proteins: A0A6P3HVI0, A4IHB9, D3ZJ25, D7PC76, O00341, O16452, O35544, O35874, O35921, O57321, P24942, P31596, P31597, P35449, P40879, P43003, P43004, P43005, P43006, P46411, P48664, P51906, P51907, P51912, P55014, P55015, P55016, P56564, P58743, Q01345, Q07782, Q10901, Q13621, Q15758, Q21353, Q21751, Q22682, Q25605, Q4R7S2, Q4R8W8

Diamond homologs: P0AFU2, P0AFU3, P32739, P39535, P46556, P70545, Q07782, Q13183, Q21339, Q28615, Q67BT3, Q86YT5, Q8CJ44, Q8WWT9, Q91Y63, Q93655, Q9BZW2, Q9ES88, Q9JHI4, Q9VDQ0, Q9VVT2, Q9Z0Z5, O59712, P25360, P72958, Q2FFH9, Q2FWY4, Q2YU56, Q49YW0, Q5HEK4, Q6G816, Q6GFE0, Q7A4P8, Q8LG88, Q8NVS5, Q99SX1, Q9UKG4, P27514, P86282

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2618 predictions. Top by Δscore:

Variant	Effect	Δscore
7:123125566:AAC:A	donor_gain	1.0000
7:123128843:A:AC	donor_gain	1.0000
7:123128844:C:CC	donor_gain	1.0000
7:123128844:CT:C	donor_gain	1.0000
7:123168502:AC:A	donor_gain	1.0000
7:123168503:CC:C	donor_gain	1.0000
7:123168558:CTTT:C	acceptor_gain	1.0000
7:123169291:C:CT	acceptor_gain	1.0000
7:123171762:ACTT:A	donor_loss	1.0000
7:123171763:CTT:C	donor_loss	1.0000
7:123171764:TTA:T	donor_loss	1.0000
7:123171765:T:TG	donor_loss	1.0000
7:123171766:A:AC	donor_gain	1.0000
7:123171766:AC:A	donor_gain	1.0000
7:123171767:C:CG	donor_gain	1.0000
7:123171767:CC:C	donor_gain	1.0000
7:123171767:CCA:C	donor_gain	1.0000
7:123171767:CCAT:C	donor_gain	1.0000
7:123171767:CCATG:C	donor_gain	1.0000
7:123171901:CCAC:C	acceptor_gain	1.0000
7:123171902:CAC:C	acceptor_gain	1.0000
7:123171902:CACC:C	acceptor_gain	1.0000
7:123171903:ACCTG:A	acceptor_loss	1.0000
7:123171904:CCTGA:C	acceptor_loss	1.0000
7:123171905:C:CA	acceptor_loss	1.0000
7:123119128:TGGC:T	donor_gain	0.9900
7:123119153:C:CT	acceptor_gain	0.9900
7:123125566:A:AC	donor_gain	0.9900
7:123125567:A:C	donor_gain	0.9900
7:123125607:G:C	donor_gain	0.9900

AlphaMissense

3868 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:123169292:A:G	W137R	0.998
7:123169292:A:T	W137R	0.998
7:123123179:A:G	W433R	0.997
7:123123179:A:T	W433R	0.997
7:123128897:A:G	W361R	0.996
7:123128897:A:T	W361R	0.996
7:123134492:A:G	W284R	0.996
7:123134492:A:T	W284R	0.996
7:123171853:A:G	C94R	0.996
7:123128864:A:G	W372R	0.995
7:123128864:A:T	W372R	0.995
7:123119126:G:C	S489R	0.994
7:123119126:G:T	S489R	0.994
7:123119128:T:G	S489R	0.994
7:123123142:A:G	L445P	0.994
7:123147185:G:C	N262K	0.994
7:123147185:G:T	N262K	0.994
7:123147219:C:T	G251D	0.994
7:123169288:A:G	L138P	0.994
7:123123177:C:A	W433C	0.993
7:123123177:C:G	W433C	0.993
7:123169284:G:C	S139R	0.993
7:123169284:G:T	S139R	0.993
7:123169286:T:G	S139R	0.993
7:123115553:A:G	W585R	0.992
7:123115553:A:T	W585R	0.992
7:123123140:C:G	A446P	0.992
7:123123145:G:T	A444D	0.992
7:123147198:C:T	G258D	0.992
7:123169297:G:A	S135F	0.992

dbSNP variants (sampled 300 via entrez): RS1000047050 (7:123159412 G>C), RS1000079295 (7:123133060 T>G), RS1000086335 (7:123170929 A>T), RS1000102944 (7:123123094 A>C), RS1000129218 (7:123113232 G>A), RS1000155489 (7:123162665 A>C), RS1000225509 (7:123123423 A>G), RS1000234338 (7:123188085 G>A), RS1000244508 (7:123113619 A>T), RS1000255461 (7:123196482 G>C,T), RS1000263765 (7:123188297 A>G), RS1000280529 (7:123156535 C>T), RS1000286527 (7:123196730 G>T), RS1000338051 (7:123133810 G>A), RS1000428369 (7:123121477 C>T)

Disease associations

OMIM: gene MIM:606193 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
sulfation-related bone disorder	Moderate	Autosomal recessive

Mondo (1): (MONDO:0019688)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001995_3	Adverse response to chemotherapy (neutropenia/leucopenia) (docetaxel)	1.000000e-06
GCST007202_18	High density lipoprotein cholesterol levels	2.000000e-06
GCST007270_11	Systolic blood pressure	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	decreases methylation	1
sulforaphane	increases expression	1
CGP 52608	increases reaction, affects binding	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Sulfates	increases uptake	1
Zinc	increases expression	1

Clinical trials (associated diseases)

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