SLC25A19 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19
Description	This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have redefined the biological function of SLC25A19. Although it was originally classified as a mitochondrial deoxyribonucleotide carrier, genetic studies on Amish families and knockout mouse models have established that SLC25A19 is in fact the mitochondrial thiamine pyrophosphate (TPP) transporter. Loss‐of‐function mutations are associated with severe developmental defects, including prenatal brain malformations, neural tube closure defects, and metabolic imbalances such as elevated alpha‑ketoglutarate levels—findings that underscore its essential role in CNS development and cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical investigations and structural modeling approaches have further elucidated key functional elements of the SLC25A19 protein. Critical amino acid residues required for substrate recognition and proper mitochondrial targeting have been identified, contesting its initial assignment as a deoxyribonucleotide carrier and firmly establishing its role in TPP transport."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": " In parallel, promoter characterization has revealed that basal transcription of SLC25A19 relies on NF‑Y binding to inverted CCAAT boxes, while its transcriptional output is adaptively modulated by nutritional (thiamine levels) and environmental factors (for example, chronic alcohol exposure) via epigenetic mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, pathogenic variants in SLC25A19 have been linked to a spectrum of neurological disorders ranging from congenital microcephaly and encephalopathy to progressive polyneuropathy; in some cases, thiamine replacement therapy has demonstrated clinical benefit."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Posttranscriptional regulation by miRNA—specifically miR‑122‑5p—adds an additional layer of control over SLC25A19 expression and function in pancreatic acinar and other cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, recent data indicate that SLC25A19 deficiency disrupts mitochondrial NADH supply, TCA cycle activity, and respiratory chain function, thereby compromising cellular bioenergetics, an insight that suggests novel therapeutic avenues such as coenzyme Q10 analog supplementation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marjorie J Rosenberg, Richa Agarwala, Gerard Bouffard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant deoxynucleotide carrier is associated with congenital microcephaly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng948"}], "href": "https://doi.org/10.1038/ng948"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12185364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12185364"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marjorie J Lindhurst, Giuseppe Fiermonte, Shiwei Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0607661103"}], "href": "https://doi.org/10.1073/pnas.0607661103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17035501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17035501"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jonghoon Kang, David C Samuels "}, {"type": "b", "children": [{"type": "t", "text": "The evidence that the DNC (SLC25A19) is not the mitochondrial deoxyribonucleotide carrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2008.01.001"}], "href": "https://doi.org/10.1016/j.mito.2008.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18280798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18280798"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ronen Spiegel, Avraham Shaag, Simon Edvardson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.21752"}], "href": "https://doi.org/10.1002/ana.21752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19798730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19798730"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jason A Zastre, Bradley S Hanberry, Rebecca L Sweet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of vitamin B1 homeostasis genes in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr Biochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jnutbio.2013.02.002"}], "href": "https://doi.org/10.1016/j.jnutbio.2013.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23642734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23642734"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Subrata Sabui, Veedamali S Subramanian, Rubina Kapadia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamem.2016.05.011"}], "href": "https://doi.org/10.1016/j.bbamem.2016.05.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27188525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27188525"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Subrata Sabui, Veedamali S Subramanian, Rubina Kapadia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptive regulation of pancreatic acinar mitochondrial thiamin pyrophosphate uptake process: possible involvement of epigenetic mechanism(s)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00192.2017"}], "href": "https://doi.org/10.1152/ajpgi.00192.2017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28729247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28729247"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yuanying Chen, Boliang Fang, Xuyun Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Orphanet J Rare Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13023-021-02028-4"}], "href": "https://doi.org/10.1186/s13023-021-02028-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34587972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34587972"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bahadir M Samur, Gülsüm Gümüş, Mehmet Canpolat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Dysmorphol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MCD.0000000000000411"}], "href": "https://doi.org/10.1097/MCD.0000000000000411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35102031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35102031"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kalidas Ramamoorthy, Subrata Sabui, Kameron I Manzon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-122-5p is involved in posttranscriptional regulation of the mitochondrial thiamin pyrophosphate transporter ("}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SLC25A19"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ") in pancreatic acinar cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00106.2023"}], "href": "https://doi.org/10.1152/ajpgi.00106.2023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37529835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37529835"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zongsheng Jiang "}, {"type": "b", "children": [{"type": "t", "text": "SLC25A19 is required for NADH homeostasis and mitochondrial respiration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2024.06.019"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2024.06.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38944213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38944213"}]}]}]}
Synonyms	MCPHA, MUP1, DNC, THMD4, THMD3
Proteins	TPC_HUMAN
NCBI Gene ID	60386
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC25A19 has 6,183 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for SLC25A19 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC25A19 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC25A19 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 SLC25A19 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 SLC25A19 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 SLC25A19 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 SLC25A19 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 SLC25A19 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC25A19 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 SLC25A19 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 SLC25A19 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SLC25A19 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC25A19 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC25A19 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 SLC25A19 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 SLC25A19 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SLC25A19 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC25A19 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC25A19 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SLC25A19 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 SLC25A19 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC25A19 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC25A19 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC25A19 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC25A19 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SLC25A19 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 SLC25A19 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving SLC25A19 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SLC25A19 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SLC25A19 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 SLC25A19 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 SLC25A19 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 SLC25A19 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC25A19 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 SLC25A19 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 SLC25A19 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC25A19 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 SLC25A19 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SLC25A19 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SLC25A19 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing SLC25A19 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SLC25A19 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.