SLC5A8

Summary

SLC5A8 (solute carrier family 5 member 8, HGNC:19119) is a protein-coding gene on chromosome 12q23.1-q23.2, encoding Sodium-coupled monocarboxylate transporter 1 (Q8N695). Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), mocarboxylate drugs (nic….

SLC5A8 has been shown to transport iodide by a passive mechanism (Rodriguez et al., 2002 [PubMed 12107270]) and monocarboxylates and short-chain fatty acids by a sodium-coupled mechanism (Gopal et al., 2004 [PubMed 15322102]). In kidney, SLC5A8 functions as a high-affinity sodium-coupled lactate transporter involved in reabsorption of lactate and maintenance of blood lactate levels (Thangaraju et al., 2006 [PubMed 16873376]).

Source: NCBI Gene 160728 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_145913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19119
Approved symbol	SLC5A8
Name	solute carrier family 5 member 8
Location	12q23.1-q23.2
Locus type	gene with protein product
Status	Approved
Aliases	AIT
Ensembl gene	ENSG00000256870
Ensembl biotype	protein_coding
OMIM	608044
Entrez	160728

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000536262, ENST00000957672, ENST00000957673

RefSeq mRNA: 1 — MANE Select: NM_145913 NM_145913

CCDS: CCDS9080

Canonical transcript exons

ENST00000536262 — 15 exons

Exon	Start	End
ENSE00002209926	101193625	101193779
ENSE00002257512	101166494	101166699
ENSE00002264111	101204500	101204565
ENSE00002269171	101155493	101157401
ENSE00002276744	101209498	101210238
ENSE00002279833	101184134	101184222
ENSE00002279919	101168096	101168182
ENSE00002281886	101195095	101195162
ENSE00002282638	101202164	101202215
ENSE00002291220	101187386	101187515
ENSE00002300529	101180029	101180096
ENSE00002301205	101161974	101162077
ENSE00002306697	101182803	101182915
ENSE00002308017	101190468	101190608
ENSE00002308986	101158249	101158328

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 87.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1146 / max 19.3109, expressed in 37 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132896	0.0357	10
132895	0.0325	15
132894	0.0236	10
132893	0.0179	9
206860	0.0050	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	87.15	gold quality
left lobe of thyroid gland	UBERON:0001120	82.31	gold quality
thyroid gland	UBERON:0002046	82.31	gold quality
right lobe of thyroid gland	UBERON:0001119	81.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.86	gold quality
adult mammalian kidney	UBERON:0000082	68.09	gold quality
cortical plate	UBERON:0005343	67.44	gold quality
kidney	UBERON:0002113	65.58	gold quality
right adrenal gland	UBERON:0001233	64.07	gold quality
left adrenal gland cortex	UBERON:0035825	64.00	gold quality
left adrenal gland	UBERON:0001234	63.44	gold quality
right adrenal gland cortex	UBERON:0035827	63.13	gold quality
adrenal gland	UBERON:0002369	60.70	gold quality
cortex of kidney	UBERON:0001225	54.28	gold quality
metanephros cortex	UBERON:0010533	53.94	gold quality
endocervix	UBERON:0000458	53.35	gold quality
prostate gland	UBERON:0002367	52.39	gold quality
islet of Langerhans	UBERON:0000006	51.77	gold quality
tonsil	UBERON:0002372	51.62	gold quality
upper lobe of left lung	UBERON:0008952	51.50	gold quality
left ovary	UBERON:0002119	49.96	gold quality
lung	UBERON:0002048	49.22	gold quality
duodenum	UBERON:0002114	49.04	gold quality
ovary	UBERON:0000992	48.94	gold quality
primary visual cortex	UBERON:0002436	45.67	silver quality
colonic epithelium	UBERON:0000397	45.28	gold quality
superior frontal gyrus	UBERON:0002661	45.27	silver quality
vermiform appendix	UBERON:0001154	45.05	silver quality
hypothalamus	UBERON:0001898	44.41	gold quality
right ovary	UBERON:0002118	43.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CDX2, CEBPB, SMAD3, SP1

miRNA regulators (miRDB)

53 targeting SLC5A8, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-657	99.48	66.02	848
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-5582-5P	99.27	71.42	1879

Literature-anchored findings (GeneRIF, showing 40)

• Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes. (hAIT, human apical iodide transporter) (PMID:12107270)
• SLC5A8 exon 1 methylation is an early event, detectable in colon adenomas & microscopic aberrant crypt foci. SLC5A8 is a member of the family of sodium solute symporters, now added to the candidate colon cancer suppressor genes. (PMID:12829793)
• functional identity of SLC5A8 as a Na(+)-coupled transporter for short-chain fatty acids. (PMID:14966140)
• In thyroid carcinomas, the mean and median hAIT mRNA levels were significantly decreased (PMID:15001644)
• Data suggest that SLC5A8 functions as a growth suppressor gene in vitro and that it is silenced frequently by epigenetic mechanisms in primary gliomas. (PMID:15867356)
• the ability of SLC5A8 to deliver butyrate into colonic epithelial cells most likely underlies the tumor suppressive role of this transporter [review] (PMID:16375929)
• Na(+)/monocarboxylate transport expression may be a favorable indicator of colorectal cancer prognosis (PMID:16670197)
• Aberrant methylation and hence silencing of TIMP3, SLC5A8, DAPK and RARbeta2, in association with BRAF mutation, may be an important step in PTC tumorigenesis and progression. (PMID:16858683)
• SMCT1(SLC5A8) may participate in the intestinal absorption of monocarboxylate drugs. (PMID:17245649)
• biophysical analysis of the stoichiometry for the Na+/monocarboxylate cotransporter SMCT1 (PMID:17526579)
• low-affinity transporter SMCT2 initiates lactate absorption in the early parts of the proximal tubule followed by the participation of the high-affinity transporter SMCT1 in the latter parts of the proximal tubule. (PMID:17692818)
• DNA methylation in the SLC5A8 promoter region suppressed the expression of SLC5A8 in prostate tumor. (PMID:18037591)
• SLC5A8 may function as a tumor suppressor gene whose silencing may contribute to carcinogenesis and progression of pancreatic cancer. (PMID:18437076)
• Frequent methylation of SLC5A8 gene is associated with head and neck squamous cell carcinoma (PMID:18559491)
• In acute myeloid leukemia with mixed lineage leukemia partial tandem duplication, the SLC5A8 tumor suppressor gene promoter was more frequently hypermethylated. (PMID:18566324)
• SLC5A8 mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in the colon (PMID:18661192)
• SMCT1 possesses a anionic leak current that becomes significant whenever external Na(+) concentration is reduced (PMID:19864324)
• Results verify IRX1, EBF3, SLC5A8, SEPT9, and FUSSEL18 as valid methylation markers in two separate sets of HNSCC specimens; also preliminarily show a trend between HPV16 positivity and target gene hypermethylation of IRX1, EBF3, SLC5A8, and SEPT9. (PMID:20029986)
• results elucidate the mechanism underlying the regulation of SLC5A8 gene transcription and also define a novel regulatory sequence that may be used to increase expression of the SLC5A8 gene in cancer gene therapy (PMID:20082847)
• Sodium-coupled electrogenic transport of pyroglutamate (5-oxoproline) via SLC5A8, a monocarboxylate transporter. (PMID:20211600)
• Efficacy of LP or their secreted soluble factors to stimulate SMCT1 expression and function and to counteract the inhibitory effects of TNF-alpha on butyrate absorption could have potential therapeutic value. (PMID:20671196)
• SLC5A8 is highly methylated in African American colon adenomas (PMID:21687703)
• SLC5A8 has a role in prostate cancer risk and aggressiveness (PMID:21802122)
• SLC5A8 nuclear translocation and loss of expression are associated with poor outcome in pancreatic ductal adenocarcinoma. (PMID:22450368)
• SLC5A8 suppresses tumour progression through depletion of survivin without involving its transport function (PMID:23167260)
• These results suggest that DNA methylation in the SLC5A8 promoter region may suppress the expression of SLC5A8 in lung tumor. (PMID:23273563)
• Data indicate oncogenic HRAS (HRAS(G12V)) as a potent mediator of SLC5A8 silencing in human nontransformed normal mammary epithelial cell lines and in mouse mammary tumors through DNMT1. (PMID:23918800)
• Gene silencing of SLC5A8 by hypermethylation was associated with poor prognosis in cases of node-negative stage I and II lung adenocarcinoma. (PMID:25827678)
• Data suggest that SLC5A8, SLC5A5 (sodium-iodide symporter), and SLC26A4 (pendrin), the 3 known iodide transporters, are important in breast tissue metabolism in lactation and in breast neoplasms. [REVIEW] (PMID:26285906)
• Underexpression of SLC5A8 is associated with hepatocellular carcinoma. (PMID:27465549)
• Human SMCT1 is regulated by insulin and SGK1. (PMID:27488665)
• Data suggest positive correlation between BMI (body mass index)/waist circumference in morbidly obese or obese subjects and jejunal mucosa mRNA abundance of SMCT1; BMI was not significantly correlated with mRNA abundance for glucose transporters SGLT1 and GLUT2 or the low-affinity short-chain fatty acid/monocarboxylate transporter SMCT2. (PMID:27801863)
• The present work reveals much lower iodide affinity in the pocket of human SMCT1 analogous to the putative iodide-binding pocket of human NIS. (PMID:29131623)
• Pendrin residues which are mutated in Pendred’s syndrome are identical to those in the aligned position of sodium/iodide symporter (NIS) and apical iodide transporter (AIT). (PMID:29772533)
• Results indicate that the SMCT1-PDZK1 interaction thus plays an important role in both lactate handling as well as urate reabsorption in the human kidney. (PMID:30604288)
• SLC5A8 expression is repressed in human cervical cancer (CC) tumors and cell lines through epigenetic silencing. (PMID:30896789)
• PDZRN3 may regulate SMCT1 function by interfering with the interaction between SMCT1 and PDZK1. (PMID:31098988)
• Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAF(V600E) mutation as biomarkers for papillary thyroid carcinoma. (PMID:32017063)
• SLC5A8 regulates the biological behaviors of cervical cancer cells through mediating the Wnt signaling pathway. (PMID:32432731)
• miR-29a, b, and c regulate SLC5A8 expression in intestinal epithelial cells. (PMID:34231393)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc5a8	ENSDARG00000087120
mus_musculus	Slc5a8	ENSMUSG00000020062
rattus_norvegicus	Slc5a8	ENSRNOG00000006367
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), SLC5A9 (ENSG00000117834), SLC5A6 (ENSG00000138074), SLC5A2 (ENSG00000140675), SLC5A12 (ENSG00000148942), SLC5A10 (ENSG00000154025), SLC5A11 (ENSG00000158865), SLC5A3 (ENSG00000198743), (ENSG00000293606)

Protein

Protein identifiers

Sodium-coupled monocarboxylate transporter 1 — Q8N695 (reviewed: Q8N695)

Alternative names: Apical iodide transporter, Electrogenic sodium monocarboxylate cotransporter, Sodium iodide-related cotransporter, Solute carrier family 5 member 8

All UniProt accessions (1): Q8N695

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate, acetoacetate and alpha-ketoisocaproate), with a Na(+):substrate stoichiometry of between 4:1 and 2:1. Catalyzes passive carrier mediated diffusion of iodide. Mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane. May be responsible for the absorption of D-lactate and monocarboxylate drugs from the intestinal tract. Acts as a tumor suppressor, suppressing colony formation in colon cancer, prostate cancer and glioma cell lines. May play a critical role in the entry of L-lactate and ketone bodies into neurons by a process driven by an electrochemical Na(+) gradient and hence contribute to the maintenance of the energy status and function of neurons. Mediates sodium-coupled electrogenic transport of pyroglutamate (5-oxo-L-proline). Can mediate the transport of chloride, bromide, iodide and nitrate ions when the external concentration of sodium ions is reduced.

Subunit / interactions. Interacts (via PDZ-binding motif) with PDZK1 (via PDZ domains 1 and 3); interaction increases nicotinate transport activity of SLC5A8.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed in normal thyroid, localized at the apical pole of thyroid cells facing the colloid lumen, but expression profoundly decreased in thyroid carcinomas. Expressed in normal colon but absent in colon aberrant crypt foci and colon cancers. Present in normal kidney cortex, brain, prostate, gastric mucosa and breast tissue but was significantly down-regulated in primary gliomas, gastric cancer, prostate tumors and breast tumors.

Activity regulation. Increase of iodide influx inhibited by addition of perchlorate (NaClO(4)), a competitive inhibitor of iodide uptake catalyzed by sodium iodide symporter (NIS). Cotransport of monocarboxylates and nicotinate strongly inhibited by probenecid, nonsteroid anti-inflammatory drugs (ibuprofen, fenoprofen, ketprofen, naproxen) in a Na(+)-dependent manner or by prolonged exposure to external concentrations of monocarboxylates.

Induction. Down-regulated in some primary cancers; due to aberrant methylation in primary colon cancers, astrocytomas and oligodendrogliomas as well as in cancers of the colon, prostate and gastric regions, and glial cell lines. Expression reactivated on treatment with a demethylating drug, 5-azacytidine.

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

RefSeq proteins (1): NP_666018* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001734	Na/solute_symporter	Family
IPR038377	Na/Glc_symporter_sf	Homologous_superfamily
IPR041992	SLC5sbd_SMCT1	Domain
IPR051163	Sodium:Solute_Symporter_SSF	Family

Pfam: PF00474

Catalyzed reactions (Rhea), 12 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• nitrate(in) = nitrate(out) (RHEA:34923)
• iodide(out) = iodide(in) (RHEA:66324)
• (S)-lactate(out) + 2 Na(+)(out) = (S)-lactate(in) + 2 Na(+)(in) (RHEA:72935)
• propanoate(out) + 2 Na(+)(out) = propanoate(in) + 2 Na(+)(in) (RHEA:72939)
• pyruvate(out) + 2 Na(+)(out) = pyruvate(in) + 2 Na(+)(in) (RHEA:72943)
• acetate(out) + 2 Na(+)(out) = acetate(in) + 2 Na(+)(in) (RHEA:72947)
• butanoate(out) + 2 Na(+)(out) = butanoate(in) + 2 Na(+)(in) (RHEA:72951)
• nicotinate(out) + 2 Na(+)(out) = nicotinate(in) + 2 Na(+)(in) (RHEA:72955)
• (R)-3-hydroxybutanoate(out) + 2 Na(+)(out) = (R)-3-hydroxybutanoate(in) + 2 Na(+)(in) (RHEA:72959)
• acetoacetate(out) + 2 Na(+)(out) = acetoacetate(in) + 2 Na(+)(in) (RHEA:72963)
• 4-methyl-2-oxopentanoate(out) + 2 Na(+)(out) = 4-methyl-2-oxopentanoate(in) + 2 Na(+)(in) (RHEA:72967)

UniProt features (79 total): helix 29, topological domain 14, transmembrane region 13, strand 10, turn 3, sequence variant 2, mutagenesis site 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7SL9	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N695-F1	85.58	0.66

Antibody-complex structures (SAbDab): 1 — 7SL9

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 (1): 485

Mutagenesis-validated functional residues (2):

Position	Phenotype
608	loss of interaction with pdzk1.
610	loss of interaction with pdzk1.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-428643	Organic anion transport by SLC5/17/25 transporters
R-HSA-9958790	SLC-mediated transport of inorganic anions
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-197264
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 112 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, WTGAAAT_UNKNOWN, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_LIPID_LOCALIZATION, GOBP_FATTY_ACID_TRANSPORT

GO Biological Process (18): monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), chloride transport (GO:0006821), acetate transport (GO:0006846), pyruvate transport (GO:0006848), apoptotic process (GO:0006915), iodide transport (GO:0015705), nitrate transmembrane transport (GO:0015706), lactate transport (GO:0015727), propanoate transmembrane transport (GO:0015730), nicotinate metabolic process (GO:1901847), nicotinate transport (GO:2001142), monocarboxylic acid transport (GO:0015718), short-chain fatty acid transmembrane transport (GO:0015913), NAD+ biosynthetic process via the salvage pathway (GO:0034355), sodium ion transmembrane transport (GO:0035725), lactate transmembrane transport (GO:0035873), transmembrane transport (GO:0055085)

GO Molecular Function (12): organic acid:sodium symporter activity (GO:0005343), monocarboxylic acid transmembrane transporter activity (GO:0008028), lactate transmembrane transporter activity (GO:0015129), propionate transmembrane transporter activity (GO:0015552), nicotinate transmembrane transporter activity (GO:0090416), monocarboxylate:sodium symporter activity (GO:0140161), iodide channel activity (GO:0160081), protein binding (GO:0005515), symporter activity (GO:0015293), solute:sodium symporter activity (GO:0015370), short-chain fatty acid transmembrane transporter activity (GO:0015636), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): GINS complex (GO:0000811), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
SLC-mediated transport of organic anions	1
SLC-mediated transmembrane transport	1
Metabolism of vitamins and cofactors	1
Metabolism	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monocarboxylic acid transport	5
monocarboxylic acid transmembrane transporter activity	3
transport	2
monoatomic anion transport	2
inorganic anion transport	2
transmembrane transport	2
short-chain fatty acid transport	2
metal ion transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nitrate import	1
organic hydroxy compound transport	1
short-chain fatty acid transmembrane transport	1
alkaloid metabolic process	1
monocarboxylic acid metabolic process	1
pyridine-containing compound metabolic process	1
nitrogen compound transport	1
carboxylic acid transport	1
fatty acid transmembrane transport	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
lactate transport	1
carboxylic acid transmembrane transport	1
cellular process	1
solute:sodium symporter activity	1
carboxylic acid transmembrane transporter activity	1
lactate transmembrane transport	1
short-chain fatty acid transmembrane transporter activity	1
propanoate transmembrane transport	1
nicotinate transport	1
organic acid:sodium symporter activity	1
monoatomic anion channel activity	1
iodide transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1

Protein interactions and networks

STRING

1379 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC5A8	SLC22A12	Q96S37	971
SLC5A8	SLC26A4	O43511	812
SLC5A8	HCAR2	Q8TDS4	786
SLC5A8	CEBPD	P49716	777
SLC5A8	SLC2A9	Q9NRM0	741
SLC5A8	SLC16A1	P53985	733
SLC5A8	SLC22A11	Q9NSA0	709
SLC5A8	FFAR2	O15552	667
SLC5A8	FFAR3	O14843	645
SLC5A8	SLC22A13	Q9Y226	622
SLC5A8	SLC16A3	O15427	618
SLC5A8	SLC16A4	O15374	600
SLC5A8	SLC16A7	O60669	581
SLC5A8	BRAF	P15056	539
SLC5A8	SLC16A14	Q7RTX9	487

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLC5A8	AQP7	psi-mi:“MI:0915”(physical association)	0.370
SLC5A8	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC5A12	PLPP3	psi-mi:“MI:0914”(association)	0.350
SLC5A8	TM9SF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): SMAP2 (Affinity Capture-MS), TSPO (Affinity Capture-MS), RAB3B (Affinity Capture-MS), CAV1 (Affinity Capture-MS), GK (Affinity Capture-MS), MTX3 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), CORO2A (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), KIAA1715 (Affinity Capture-MS), TVP23C (Affinity Capture-MS), GPR89A (Affinity Capture-MS), SLC25A46 (Affinity Capture-MS), MCU (Affinity Capture-MS)

ESM2 similar proteins: A0FKN5, D7PC76, O00341, O04289, O35874, O43511, O57321, O70531, P24942, P31597, P40879, P43003, P43005, P46411, P50443, P51906, P51907, P53391, P53392, P56564, P58743, Q62273, Q65AC2, Q69DJ1, Q7SYH5, Q7T2C4, Q8BYF6, Q8CIW6, Q8GYH8, Q8JZR4, Q8N695, Q924C9, Q94LW6, Q95135, Q99NH7, Q9BEG8, Q9BXS9, Q9EPH0, Q9FEP7, Q9FY46

Diamond homologs: A7MBD8, O70247, P83740, Q1EHB4, Q3ZMH1, Q49B93, Q5BL81, Q5U4D8, Q63008, Q7SYH5, Q7T384, Q8BYF6, Q8N695, Q92911, Q99PN0, Q9XT77, Q9Y289, Q5E733

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CEBPB	“up-regulates quantity by expression”	SLC5A8	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	SLC5A8	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2331 predictions. Top by Δscore:

Variant	Effect	Δscore
12:101157402:C:CC	acceptor_gain	1.0000
12:101158248:CTTT:C	donor_gain	1.0000
12:101166580:ACAG:A	donor_gain	1.0000
12:101166581:CAGC:C	donor_gain	1.0000
12:101168094:A:AC	donor_gain	1.0000
12:101168095:C:CC	donor_gain	1.0000
12:101182801:A:AC	donor_gain	1.0000
12:101182802:C:CC	donor_gain	1.0000
12:101182805:ATT:A	donor_gain	1.0000
12:101182911:CTGTG:C	acceptor_gain	1.0000
12:101193623:A:AC	donor_gain	1.0000
12:101193623:ACTT:A	donor_gain	1.0000
12:101193624:C:CC	donor_gain	1.0000
12:101193624:CTT:C	donor_gain	1.0000
12:101193624:CTTC:C	donor_gain	1.0000
12:101193626:T:TA	donor_gain	1.0000
12:101193779:CCTT:C	acceptor_gain	1.0000
12:101209492:CCTTA:C	donor_loss	1.0000
12:101209493:CTTA:C	donor_loss	1.0000
12:101209494:TTA:T	donor_loss	1.0000
12:101209495:TAC:T	donor_loss	1.0000
12:101209496:ACC:A	donor_loss	1.0000
12:101158247:A:AC	donor_gain	0.9900
12:101158248:C:CC	donor_gain	0.9900
12:101168095:CA:C	donor_gain	0.9900
12:101168095:CAA:C	donor_gain	0.9900
12:101168095:CAAT:C	donor_gain	0.9900
12:101168095:CAATT:C	donor_gain	0.9900
12:101168179:CTGC:C	acceptor_gain	0.9900
12:101168183:C:CA	acceptor_loss	0.9900

AlphaMissense

3950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:101190491:A:C	C270W	0.999
12:101209657:G:C	S64R	0.999
12:101209657:G:T	S64R	0.999
12:101209659:T:G	S64R	0.999
12:101209667:A:G	L61P	0.999
12:101180084:C:T	G393E	0.998
12:101182900:A:C	S356R	0.998
12:101182900:A:T	S356R	0.998
12:101182902:T:G	S356R	0.998
12:101182915:G:C	S351R	0.998
12:101182915:G:T	S351R	0.998
12:101184135:T:G	S351R	0.998
12:101184143:C:T	G348E	0.998
12:101184144:C:A	G348W	0.998
12:101184145:A:C	S347R	0.998
12:101184145:A:T	S347R	0.998
12:101184147:T:G	S347R	0.998
12:101190492:C:T	C270Y	0.998
12:101190503:T:A	R266S	0.998
12:101190503:T:G	R266S	0.998
12:101190574:A:G	W243R	0.998
12:101190574:A:T	W243R	0.998
12:101202202:C:T	G144E	0.998
12:101202203:C:G	G144R	0.998
12:101202203:C:T	G144R	0.998
12:101209507:G:C	S114R	0.998
12:101209507:G:T	S114R	0.998
12:101209509:T:G	S114R	0.998
12:101209552:G:C	S99R	0.998
12:101209552:G:T	S99R	0.998

dbSNP variants (sampled 300 via entrez): RS1000060089 (12:101184889 A>G), RS1000183550 (12:101208080 T>C), RS1000186262 (12:101182640 A>G), RS1000267479 (12:101182153 T>C), RS1000271865 (12:101160764 A>G), RS1000330644 (12:101172167 A>G), RS1000501291 (12:101177931 T>C), RS1000652758 (12:101183277 C>A,T), RS1000708812 (12:101189769 A>G), RS1000722624 (12:101200931 C>T), RS1000793514 (12:101184313 G>A), RS1000946859 (12:101191092 A>T), RS1000963031 (12:101177995 A>G), RS1001020408 (12:101155720 A>C), RS1001068918 (12:101196609 A>G,T)

Disease associations

OMIM: gene MIM:608044 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002337_25	Amyotrophic lateral sclerosis (sporadic)	5.000000e-06
GCST009305_6	California verbal learning test score	5.000000e-06
GCST90020024_234	A body shape index	1.000000e-08
GCST90020027_1676	Waist-hip index	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

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 — Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
fenoprofen	Inhibition	4.57	pIC50
ibuprofen	Inhibition	4.2	pIC50
ketoprofen	Inhibition	3.92	pIC50

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Ibuprofen	decreases activity	2
terbufos	increases methylation	1
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	affects expression, affects methylation	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Butyrates	affects cotreatment, increases transport	1
Caffeine	increases phosphorylation	1
Carboxylic Acids	affects cotreatment, increases transport	1
Cisplatin	decreases response to substance, increases expression	1
Fonofos	increases methylation	1
Fatty Acids, Volatile	affects cotreatment, increases transport	1
Hydrogen Peroxide	affects expression	1
Nicotinic Acids	affects cotreatment, increases transport	1
Parathion	increases methylation	1
Probenecid	decreases activity	1
Propionates	affects cotreatment, increases transport	1
Smoke	increases abundance, increases expression	1
Sodium	affects cotreatment, increases transport	1
Tobacco Smoke Pollution	affects expression	1
Valerates	affects cotreatment, increases transport	1
Lactic Acid	affects cotreatment, increases transport	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4U5	HuH7-SLC5A8-KO-c2	Cancer cell line	Male
CVCL_D4U6	HuH7-SLC5A8-KO-c3	Cancer cell line	Male

Clinical trials (associated diseases)

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