SLC5A9

Summary

SLC5A9 (solute carrier family 5 member 9, HGNC:22146) is a protein-coding gene on chromosome 1p33, encoding Sodium/glucose cotransporter 4 (Q2M3M2). Electrogenic Na(+)-coupled sugar symporter that may play a primary role in D-mannose and possibly D-fructose and D-glucose transport at the plasma membrane.

Predicted to enable D-glucose:sodium symporter activity. Predicted to be involved in hexose transmembrane transport. Located in extracellular exosome.

Source: NCBI Gene 200010 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_001011547

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22146
Approved symbol	SLC5A9
Name	solute carrier family 5 member 9
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	SGLT4
Ensembl gene	ENSG00000117834
Ensembl biotype	protein_coding
OMIM	620216
Entrez	200010

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000236495, ENST00000425816, ENST00000438567, ENST00000441260, ENST00000471020, ENST00000493837, ENST00000525901, ENST00000527929, ENST00000532322, ENST00000533824, ENST00000906153, ENST00000906154

RefSeq mRNA: 2 — MANE Select: NM_001011547 NM_001011547, NM_001135181

CCDS: CCDS30709, CCDS44136

Canonical transcript exons

ENST00000438567 — 14 exons

Exon	Start	End
ENSE00000771858	48228850	48228954
ENSE00000771859	48229295	48229459
ENSE00000771862	48231946	48232151
ENSE00001925970	48247335	48248638
ENSE00003514780	48235729	48235879
ENSE00003545034	48233655	48233762
ENSE00003589175	48231545	48231625
ENSE00003603520	48237679	48237847
ENSE00003625040	48224724	48224795
ENSE00003638422	48232367	48232502
ENSE00003668643	48230600	48230705
ENSE00003671769	48239322	48239537
ENSE00003679777	48242457	48242616
ENSE00003903693	48222716	48222898

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 96.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4096 / max 191.2281, expressed in 49 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2788	0.3825	44
2789	0.0271	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	96.89	gold quality
jejunal mucosa	UBERON:0000399	94.27	gold quality
duodenum	UBERON:0002114	91.29	gold quality
kidney epithelium	UBERON:0004819	90.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.09	gold quality
small intestine	UBERON:0002108	88.28	gold quality
sperm	CL:0000019	83.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.01	gold quality
right lung	UBERON:0002167	81.79	gold quality
right lobe of liver	UBERON:0001114	81.53	gold quality
epithelial cell of pancreas	CL:0000083	80.06	silver quality
sural nerve	UBERON:0015488	79.95	gold quality
tibial nerve	UBERON:0001323	78.41	gold quality
mucosa of stomach	UBERON:0001199	78.12	gold quality
body of pancreas	UBERON:0001150	77.84	gold quality
liver	UBERON:0002107	77.51	gold quality
adult mammalian kidney	UBERON:0000082	77.12	gold quality
metanephros cortex	UBERON:0010533	76.46	gold quality
endocervix	UBERON:0000458	76.27	gold quality
kidney	UBERON:0002113	76.13	gold quality
cortex of kidney	UBERON:0001225	75.77	gold quality
upper lobe of left lung	UBERON:0008952	75.55	gold quality
jejunum	UBERON:0002115	75.48	gold quality
upper arm skin	UBERON:0004263	75.30	gold quality
upper lobe of lung	UBERON:0008948	75.27	gold quality
pancreatic ductal cell	CL:0002079	75.25	silver quality
apex of heart	UBERON:0002098	74.56	gold quality
left ovary	UBERON:0002119	74.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.52	gold quality
right ovary	UBERON:0002118	74.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting SLC5A9, 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-4262	100.00	73.26	3931
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254

Literature-anchored findings (GeneRIF, showing 1)

• SGLT4 would have unique physiological functions (i.e., absorption and/or reabsorption of Man, 1,5AG, and Fru, in addition to Glc). (PMID:15607332)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc5a9	ENSDARG00000005518
mus_musculus	Slc5a9	ENSMUSG00000028544
rattus_norvegicus	Slc5a9	ENSRNOG00000042950
drosophila_melanogaster	CG2187	FBGN0017448
drosophila_melanogaster	rumpel	FBGN0029950
drosophila_melanogaster	SLC5A11	FBGN0031998
drosophila_melanogaster	bumpel	FBGN0037895
drosophila_melanogaster	ChT	FBGN0038641
drosophila_melanogaster	salt	FBGN0039872
drosophila_melanogaster	Smvt	FBGN0039873
drosophila_melanogaster	CG31262	FBGN0051262
drosophila_melanogaster	CG31668	FBGN0051668
drosophila_melanogaster	CG33124	FBGN0053124
drosophila_melanogaster	kumpel	FBGN0250757
caenorhabditis_elegans		WBGENE00000501

Paralogs (12): SLC5A1 (ENSG00000100170), SLC5A4 (ENSG00000100191), SLC5A5 (ENSG00000105641), SLC5A7 (ENSG00000115665), SLC5A6 (ENSG00000138074), SLC5A2 (ENSG00000140675), SLC5A12 (ENSG00000148942), SLC5A10 (ENSG00000154025), SLC5A11 (ENSG00000158865), SLC5A3 (ENSG00000198743), SLC5A8 (ENSG00000256870), (ENSG00000293606)

Protein

Protein identifiers

Sodium/glucose cotransporter 4 — Q2M3M2 (reviewed: Q2M3M2)

Alternative names: Solute carrier family 5 member 9

All UniProt accessions (4): Q2M3M2, F8WD86, H0Y5P9, H0YC92

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic Na(+)-coupled sugar symporter that may play a primary role in D-mannose and possibly D-fructose and D-glucose transport at the plasma membrane. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Exclusively recognizes sugar substrates having a pyranose ring with an axial hydroxyl group on carbon 2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the small intestine, kidney and liver.

Similarity. Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2M3M2-1	1	yes
Q2M3M2-2	2
Q2M3M2-3	3

RefSeq proteins (2): NP_001011547, NP_001128653 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001734	Na/solute_symporter	Family
IPR018212	Na/solute_symporter_CS	Conserved_site
IPR038377	Na/Glc_symporter_sf	Homologous_superfamily

Pfam: PF00474

Catalyzed reactions (Rhea), 1 shown:

• D-mannose(out) + n Na(+)(out) = D-mannose(in) + n Na(+)(in) (RHEA:75475)

UniProt features (40 total): topological domain 14, transmembrane region 14, sequence variant 4, modified residue 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M3M2-F1	83.54	0.54

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 (2): 604, 605

Glycosylation sites (1): 251

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-382551	Transport of small molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 93 (showing top): GOBP_CARBOHYDRATE_TRANSPORT, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SUGAR_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): hexose transmembrane transport (GO:0008645), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (7): low-affinity D-glucose:sodium symporter activity (GO:0005362), D-glucose:sodium symporter activity (GO:0005412), carbohydrate:monoatomic cation symporter activity (GO:0005402), hexose transmembrane transporter activity (GO:0015149), symporter activity (GO:0015293), solute:sodium symporter activity (GO:0015370), transmembrane transporter activity (GO:0022857)

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
solute:monoatomic cation symporter activity	2
monosaccharide transmembrane transport	1
metal ion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
cellular process	1
D-glucose:sodium symporter activity	1
carbohydrate:monoatomic cation symporter activity	1
solute:sodium symporter activity	1
D-glucose transmembrane transporter activity	1
carbohydrate transmembrane transporter activity	1
hexose transmembrane transport	1
monosaccharide transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

831 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC5A9	SLC2A2	P11168	554
SLC5A9	SLC2A5	P22732	551
SLC5A9	GARIN5A	Q6IPT2	533
SLC5A9	SLC2A7	Q6PXP3	507
SLC5A9	H7C1H1	H7C1H1	501
SLC5A9	SLC2A11	Q9BYW1	501
SLC5A9	WDR25	Q64LD2	493
SLC5A9	SLC2A8	Q9NY64	461
SLC5A9	TRABD2B	A6NFA1	460
SLC5A9	FAM8A1	Q9UBU6	460
SLC5A9	SLC25A45	Q8N413	452
SLC5A9	ANKRD50	Q9ULJ7	451
SLC5A9	SLC16A13	Q7RTY0	447
SLC5A9	TPRA1	Q86W33	445
SLC5A9	PDHA2	P29803	437

IntAct

7 interactions, top by confidence:

A	B	Type	Score
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
SLC5A9	CD63	psi-mi:“MI:0914”(association)	0.530
KLF8		psi-mi:“MI:0914”(association)	0.350
NTRK1	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC5A9	RER1	psi-mi:“MI:0914”(association)	0.350
SLC6A1	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): CD63 (Affinity Capture-MS), GIF (Affinity Capture-MS), SLC5A9 (Affinity Capture-MS), SLC5A9 (Affinity Capture-MS), SLC5A9 (Affinity Capture-MS), LPHN1 (Affinity Capture-MS), ATP5E (Affinity Capture-MS), USMG5 (Affinity Capture-MS), ATP5I (Affinity Capture-MS), ATP5H (Affinity Capture-MS), ATP5J (Affinity Capture-MS), CD63 (Affinity Capture-MS), CERS1 (Affinity Capture-MS), CHPT1 (Affinity Capture-MS), FZD8 (Affinity Capture-MS)

ESM2 similar proteins: A0PJK1, A8I1B9, A8WHP3, B9NAE4, D3ZIS0, O02228, O77741, P11170, P13866, P26429, P26430, P31636, P31637, P31639, P41251, P49279, P49280, P53790, P53791, P53792, P53793, P53794, P56436, P70553, P83740, Q27946, Q27981, Q28610, Q28728, Q2M3M2, Q3ZC26, Q5FY69, Q5SWY8, Q6R4Q5, Q7T384, Q8BGY9, Q8C3K6, Q8K0E3, Q8UWF0, Q8VDT1

Diamond homologs: A0PJK1, A8I1B9, A8WHP3, D3ZIS0, P11170, P13866, P26429, P26430, P31636, P31637, P31639, P53790, P53791, P53792, P53793, P53794, P96169, Q28610, Q28728, Q2M3M2, Q3ZC26, Q5FY69, Q5SWY8, Q6R4Q5, Q8C3K6, Q8K0E3, Q8VDT1, Q8WWX8, Q91ZP4, Q923I7, Q9ET37, Q9JKZ2, Q9NY91, Q9Z1F2, P31448

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	14
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

2094 predictions. Top by Δscore:

Variant	Effect	Δscore
1:48222897:GG:G	donor_gain	1.0000
1:48222897:GGGT:G	donor_loss	1.0000
1:48222898:GG:G	donor_gain	1.0000
1:48222898:GGTA:G	donor_loss	1.0000
1:48222899:G:GG	donor_gain	1.0000
1:48222900:T:G	donor_loss	1.0000
1:48224796:G:GG	donor_gain	1.0000
1:48227893:G:GT	donor_gain	1.0000
1:48227912:GACAT:G	donor_gain	1.0000
1:48227913:ACATA:A	donor_gain	1.0000
1:48228960:G:GT	donor_gain	1.0000
1:48231539:CCCCA:C	acceptor_loss	1.0000
1:48231540:CCCAG:C	acceptor_loss	1.0000
1:48231541:CCAG:C	acceptor_loss	1.0000
1:48231542:CA:C	acceptor_loss	1.0000
1:48231543:A:T	acceptor_loss	1.0000
1:48231624:GG:G	donor_gain	1.0000
1:48231625:GG:G	donor_gain	1.0000
1:48231625:GGTA:G	donor_loss	1.0000
1:48231626:G:GA	donor_loss	1.0000
1:48231627:T:A	donor_loss	1.0000
1:48231631:G:GT	donor_gain	1.0000
1:48232501:AGG:A	donor_loss	1.0000
1:48232503:G:GA	donor_loss	1.0000
1:48232503:G:GG	donor_gain	1.0000
1:48232504:T:A	donor_loss	1.0000
1:48233653:A:AG	acceptor_gain	1.0000
1:48233654:G:GG	acceptor_gain	1.0000
1:48233654:GAC:G	acceptor_gain	1.0000
1:48233654:GACGA:G	acceptor_gain	1.0000

AlphaMissense

4409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:48237707:A:C	S441R	0.999
1:48237709:C:A	S441R	0.999
1:48237709:C:G	S441R	0.999
1:48232484:A:C	S339R	0.998
1:48232486:C:A	S339R	0.998
1:48232486:C:G	S339R	0.998
1:48235773:A:C	S396R	0.998
1:48235775:C:A	S396R	0.998
1:48235775:C:G	S396R	0.998
1:48235797:A:C	S404R	0.997
1:48235799:C:A	S404R	0.997
1:48235799:C:G	S404R	0.997
1:48228871:A:C	S86R	0.996
1:48228873:C:A	S86R	0.996
1:48228873:C:G	S86R	0.996
1:48228883:A:C	S90R	0.996
1:48228885:T:A	S90R	0.996
1:48228885:T:G	S90R	0.996
1:48228913:G:T	G100W	0.996
1:48228943:T:C	F110L	0.996
1:48228945:C:A	F110L	0.996
1:48228945:C:G	F110L	0.996
1:48235800:A:C	S405R	0.996
1:48235802:C:A	S405R	0.996
1:48235802:C:G	S405R	0.996
1:48228863:T:C	L83P	0.995
1:48233729:T:G	Y370D	0.995
1:48237716:T:A	W444R	0.995
1:48237716:T:C	W444R	0.995
1:48237756:T:G	F457C	0.995

dbSNP variants (sampled 300 via entrez): RS1000013850 (1:48240702 A>C,T), RS1000139813 (1:48241128 T>C), RS1000223891 (1:48225553 C>T), RS1000256565 (1:48247646 C>G), RS1000339502 (1:48228657 C>T), RS1000447909 (1:48241716 C>T), RS1000895124 (1:48228420 G>A), RS1000925011 (1:48242026 C>G,T), RS1000953142 (1:48235045 G>A), RS1001017774 (1:48242282 T>C,G), RS1001067054 (1:48246904 C>T), RS1001179617 (1:48222293 CTT>C), RS1001285800 (1:48228765 C>T), RS1001297296 (1:48248872 T>TACA), RS1001474249 (1:48246046 T>C)

Disease associations

OMIM: gene MIM:620216 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1151	Metabolite levels	9.000000e-08
GCST009733_41	Urinary metabolite levels in chronic kidney disease	4.000000e-24
GCST010219_3	Attention deficit hyperactivity disorder (inattention symptoms)	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010459	aminoadipic acid measurement
EFO:0005116	urinary metabolite measurement

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 — Hexose transporter family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment	4
Cyclosporine	decreases expression	4
Aflatoxin B1	decreases expression, decreases methylation, affects expression	3
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Ethanol	affects cotreatment, increases expression	1
Aldehydes	decreases expression	1
Azathioprine	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Endosulfan	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Quercetin	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_D4U7	HuH7-SLC5A9-KO-c13	Cancer cell line	Male
CVCL_D4U8	HuH7-SLC5A9-KO-c7	Cancer cell line	Male

Clinical trials (associated diseases)

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