SLC25A22 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 25 (mitochondrial carrier: glutamate), member 22
Description	This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jul 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC25A22 encodes a mitochondrial glutamate transporter that plays a crucial role in cellular metabolism. In colorectal cancer cells, particularly those harboring KRAS mutations, SLC25A22 facilitates glutaminolysis by mediating the mitochondrial import of glutamate, thereby promoting the conversion of glutamine to α‐ketoglutarate and other metabolic intermediates. This metabolic reprogramming contributes to epigenetic alterations—via suppression of demethylase activity—that enhance cellular proliferation and stem cell–like features. In these contexts, SLC25A22 has been identified as a synthetic lethal gene, offering a potential target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cancer, mutations in SLC25A22 have been linked to severe neonatal epileptic encephalopathies and migrating partial seizures in infancy. Loss-of-function variants significantly impair the transporter’s ability to import glutamate into mitochondria, which is essential not only for normal neuronal function but also for processes such as deamination of amino acids in the liver. Affected patients exhibit profound developmental delays, refractory seizures (often with suppression burst patterns on electroencephalograms), hypotonia, microcephaly, and in some cases, metabolic disturbances such as hyperprolinaemia and intracellular lipid accumulation. These phenotypes illustrate the broad impact of SLC25A22 dysfunction on both neurodevelopment and systemic metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, SLC25A22 overexpression has been implicated in driving osteosarcoma progression. Elevated levels of this transporter correlate with increased cell proliferation, invasion, and metastatic potential, particularly to the lungs. Mechanistic investigations indicate that SLC25A22 promotes tumorigenesis by inhibiting the PTEN signaling pathway, which in turn leads to enhanced phosphorylation of AKT and FAK, accelerated cell cycle progression, and reduced apoptosis. This oncogenic activity underscores a critical role for SLC25A22 not only as a metabolic facilitator but also as a direct contributor to tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chi Chun Wong, Yun Qian, Xiaona Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC25A22 Promotes Proliferation and Survival of Colorectal Cancer Cells With KRAS Mutations and Xenograft Tumor Progression in Mice via Intracellular Synthesis of Aspartate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2016.07.011"}], "href": "https://doi.org/10.1053/j.gastro.2016.07.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27451147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27451147"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chi Chun Wong, Jiaying Xu, Xiqing Bian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In Colorectal Cancer Cells With Mutant KRAS, SLC25A22-Mediated Glutaminolysis Reduces DNA Demethylation to Increase WNT Signaling, Stemness, and Drug Resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2020.08.016"}], "href": "https://doi.org/10.1053/j.gastro.2020.08.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32814111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32814111"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "F Molinari, A Kaminska, G Fiermonte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2009.01236.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2009.01236.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19780765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19780765"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Annapurna Poduri, Erin L Heinzen, Vida Chitsazzadeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC25A22 is a novel gene for migrating partial seizures in infancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.23998"}], "href": "https://doi.org/10.1002/ana.23998"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24596948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24596948"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Emma S Reid, Hywel Williams, Glenn Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SLC25A22: hyperprolinaemia, vacuolated fibroblasts and presentation with developmental delay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-017-0025-7"}], "href": "https://doi.org/10.1007/s10545-017-0025-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28255779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28255779"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Camille Lemattre, Marion Imbert-Bouteille, Vincent Gatinois, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Report on three additional patients and genotype-phenotype correlation in SLC25A22-related disorders group."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-019-0433-2"}], "href": "https://doi.org/10.1038/s41431-019-0433-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31285529"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31285529"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ming-Wei Chen, Xue-Jian Wu "}, {"type": "b", "children": [{"type": "t", "text": "SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Technol Cancer Res Treat (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1533033818811143"}], "href": "https://doi.org/10.1177/1533033818811143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30482097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30482097"}]}]}]}
Synonyms	NET44, GC-1, EIEE3
Proteins	GHC1_HUMAN
NCBI Gene ID	79751
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC25A22 has 6,499 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 118 datasets.

Click the + buttons to view associations for SLC25A22 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving SLC25A22 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC25A22 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 SLC25A22 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 SLC25A22 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC25A22 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 SLC25A22 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SLC25A22 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SLC25A22 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 SLC25A22 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC25A22 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 SLC25A22 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SLC25A22 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SLC25A22 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SLC25A22 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC25A22 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC25A22 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SLC25A22 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC25A22 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC25A22 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SLC25A22 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 SLC25A22 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving SLC25A22 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SLC25A22 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SLC25A22 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 SLC25A22 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 SLC25A22 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 SLC25A22 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC25A22 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SLC25A22 protein from the curated DrugBank Drug Targets dataset.