SLC5A3 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 5 (sodium/myo-inositol cotransporter), member 3
Description	Enables myo-inositol:sodium symporter activity; potassium channel regulator activity; and transmembrane transporter binding activity. Predicted to be involved in several processes, including inositol metabolic process; monosaccharide transmembrane transport; and myo-inositol import across plasma membrane. Predicted to act upstream of or within several processes, including positive regulation of protein localization to membrane; positive regulation of reactive oxygen species biosynthetic process; and regulation of respiratory gaseous exchange. Located in perinuclear region of cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC5A3, the sodium/myo‐inositol co‐transporter (commonly known as SMIT1), is emerging as a multifunctional protein with roles that extend beyond conventional osmolyte transport. Genetic studies have implicated its chromosomal region (21q22, near MRPS6‐SLC5A3‐KCNE2) in increased susceptibility to myocardial infarction, suggesting that SLC5A3 may have broader clinical relevance in cardiovascular disease (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the cellular level, SLC5A3 is a key mediator of myo‐inositol uptake in response to osmotic stress. Under hypotonic conditions, its recruitment to the plasma membrane increases the myo‐inositol permeability of cells, thereby contributing to cellular volume regulation. Its activity is further regulated by signaling molecules such as JAK2 during hyperosmotic shock, positioning SLC5A3 as an important sensor and effector in osmotic adaptation (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]). In addition, by supplying myo‐inositol, SLC5A3 indirectly enlarges intracellular pools of phosphatidylinositol 4,5‐bisphosphate (PI[4,5]P2), thereby modulating the activity of PI(4,5)P2‐dependent ion channels and altering cellular excitability (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]). Moreover, physical interactions between SLC5A3 and voltage‐gated KCNQ potassium channels have been shown to modify channel ion selectivity, gating kinetics, and pharmacology independent of the transporter’s substrate translocation function (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant expression of SLC5A3 is also implicated in various pathological states. In skeletal muscle, SLC5A3 overexpression is observed in sporadic inclusion body myositis (IBM), where its abnormal localization to muscle membranes and proximity to protein inclusions correlate with inflammatory cell infiltration, hinting at a potential role in muscle degeneration and protein aggregation (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]). In the arena of oncology, elevated SLC5A3 expression in non‐small cell lung cancer and cervical cancer supports tumor progression by maintaining intracellular myo‐inositol levels that promote Akt–mTOR signaling, thereby enhancing cell proliferation, migration, and survival. Conversely, depletion of SLC5A3 reduces myo‐inositol content, dampens Akt–mTOR activity, and induces oxidative injury and cell death, underscoring its potential as a therapeutic target (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sekar Kathiresan, Benjamin F Voight, Shaun Purcell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.327"}], "href": "https://doi.org/10.1038/ng.327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19198609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19198609"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zohreh Hosseinzadeh, Shefalee K Bhavsar, Florian Lang "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of the myoinositol transporter SMIT by JAK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000343335"}], "href": "https://doi.org/10.1159/000343335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23207989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23207989"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Joseph Andronic, Ryo Shirakashi, Simone U Pickel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypotonic activation of the myo-inositol transporter SLC5A3 in HEK293 cells probed by cell volumetry, confocal and super-resolution microscopy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0119990"}], "href": "https://doi.org/10.1371/journal.pone.0119990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25756525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25756525"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gucan Dai, Haijie Yu, Martin Kruse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1606348113"}], "href": "https://doi.org/10.1073/pnas.1606348113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27217553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27217553"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rían W Manville, Daniel L Neverisky, Geoffrey W Abbott "}, {"type": "b", "children": [{"type": "t", "text": "SMIT1 Modifies KCNQ Channel Function and Pharmacology by Physical Interaction with the Pore."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biophys J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bpj.2017.06.055"}], "href": "https://doi.org/10.1016/j.bpj.2017.06.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28793216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28793216"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Boel De Paepe, Caroline Merckx, Jana Jarošová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myo-Inositol Transporter SLC5A3 Associates with Degenerative Changes and Inflammation in Sporadic Inclusion Body Myositis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom10040521"}], "href": "https://doi.org/10.3390/biom10040521"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32235474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32235474"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zihan Cui, Chuanyong Mu, Zhichao Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The sodium/myo-inositol co-transporter SLC5A3 promotes non-small cell lung cancer cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-022-05017-y"}], "href": "https://doi.org/10.1038/s41419-022-05017-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35760803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35760803"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Li Li, Fang-Rong Shen, Qunxian Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC5A3 is important for cervical cancer cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.84570"}], "href": "https://doi.org/10.7150/ijbs.84570"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37324953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37324953"}]}]}]}
Synonyms	SMIT, SMIT1, SMIT2, BCW2
Proteins	SC5A3_HUMAN
NCBI Gene ID	6526
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC5A3 has 9,994 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for SLC5A3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC5A3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SLC5A3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC5A3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC5A3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SLC5A3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SLC5A3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SLC5A3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC5A3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC5A3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC5A3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC5A3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SLC5A3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC5A3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC5A3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SLC5A3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SLC5A3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC5A3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC5A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SLC5A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SLC5A3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SLC5A3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC5A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC5A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SLC5A3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SLC5A3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SLC5A3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC5A3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC5A3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC5A3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SLC5A3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SLC5A3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SLC5A3 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SLC5A3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SLC5A3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SLC5A3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SLC5A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC5A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SLC5A3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC5A3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC5A3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SLC5A3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.