NDUFC2 Gene

HGNC Family	Mitochondrial respiratory chain complexes
Name	NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa
Description	Predicted to enable NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial inner membrane and respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have shown that NDUFC2, a nuclear‐encoded subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase), is subject to dynamic gene regulatory mechanisms in both metabolic and oncologic settings. Differential DNA methylation of the NDUFC2 promoter in skeletal muscle has been observed in individuals with a family history of type 2 diabetes, with exercise intervention reducing methylation and thereby potentially enhancing gene expression. Other investigations have noted altered expression levels of NDUFC2 in tissues from thyroid and colorectal cancers, suggesting that its regulation may influence cellular metabolic states across diverse pathological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt its core, NDUFC2 plays an essential role in the proper assembly and function of mitochondrial complex I. Cellular models with reduced NDUFC2 levels, whether due to genetic variants or targeted knockdown, exhibit marked mitochondrial dysfunction characterized by impaired complex I activity, disrupted cristae structure, and excessive reactive oxygen species production. In addition, patients with pathogenic NDUFC2 mutations, as seen in cases of Leigh syndrome, manifest severe complex I deficiency, emphasizing the subunit’s critical contribution to the biogenesis of the membrane arm of the enzyme and overall mitochondrial integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeficient NDUFC2 expression has also been implicated in cardiovascular and cerebrovascular disorders. In circulating mononuclear cells from patients with acute coronary syndrome, reduced NDUFC2 expression was associated with compromised mitochondrial function and diminished antioxidant defenses. Similarly, in hypertensive patients, a specific NDUFC2 genetic variant correlates with left ventricular hypertrophy, while experimental ischemia-reperfusion models reveal that NDUFC2 downregulation triggers activation of the inflammatory NLRP3 pathway and endothelial-to-mesenchymal transition, further aggravating vascular injury. These observations collectively position NDUFC2 as a molecular nexus linking mitochondrial dysfunction to increased oxidative stress and inflammation in cardiovascular disease and stroke."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yusuf Ziya Igci, Ahmet Arslan, Ersin Akarsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Pathol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12022-011-9157-8"}], "href": "https://doi.org/10.1007/s12022-011-9157-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21509594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21509594"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marloes Dekker Nitert, Tasnim Dayeh, Peter Volkov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db11-1653"}], "href": "https://doi.org/10.2337/db11-1653"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23028138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23028138"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Y Z Igci, E Bozgeyik, E Borazan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression profiling of SCN8A and NDUFC2 genes in colorectal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Oncol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25804238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25804238"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Salvatore Raffa, Cristina Scrofani, Sabatino Valente, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vitro characterization of mitochondrial function and structure in rat and human cells with a deficiency of the NADH: ubiquinone oxidoreductase Ndufc2 subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddx333"}], "href": "https://doi.org/10.1093/hmg/ddx333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28973657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28973657"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ahmad Alahmad, Alessia Nasca, Juliana Heidler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome and stalled biogenesis of complex I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/emmm.202012619"}], "href": "https://doi.org/10.15252/emmm.202012619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32969598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32969598"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Salvatore Raffa, Xiao Lan Diana Chin, Rosita Stanzione, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The reduction of NDUFC2 expression is associated with mitochondrial impairment in circulating mononuclear cells of patients with acute coronary syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cardiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijcard.2019.02.027"}], "href": "https://doi.org/10.1016/j.ijcard.2019.02.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30808603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30808603"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jianwei Chen, Xiaoyu Liu, Ran Bi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDUFC2 deficiency exacerbates endothelial mesenchymal transformation during ischemia-reperfusion via NLRP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroreport (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/WNR.0000000000001940"}], "href": "https://doi.org/10.1097/WNR.0000000000001940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37506315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37506315"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Giovanna Gallo, Maurizio Forte, Maria Cotugno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphic variants at NDUFC2, encoding a mitochondrial complex I subunit, associate with cardiac hypertrophy in human hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s10020-023-00701-x"}], "href": "https://doi.org/10.1186/s10020-023-00701-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37558995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37558995"}]}]}]}
Synonyms	CI-B14.5B, B14.5B, HLC-1, NADHDH2
Proteins	NDUC2_HUMAN
NCBI Gene ID	4718
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NDUFC2 has 5,614 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for NDUFC2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 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 NDUFC2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NDUFC2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NDUFC2 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 NDUFC2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NDUFC2 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 NDUFC2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NDUFC2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NDUFC2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NDUFC2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NDUFC2 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 NDUFC2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing NDUFC2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NDUFC2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NDUFC2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NDUFC2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NDUFC2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NDUFC2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NDUFC2 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 NDUFC2 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 NDUFC2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DrugBank Drug Targets	interacting drugs for NDUFC2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NDUFC2 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 NDUFC2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NDUFC2 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 NDUFC2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NDUFC2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NDUFC2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NDUFC2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NDUFC2 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 NDUFC2 from the GeneSigDB Published Gene Signatures dataset.