TMEM70 Gene

Name	transmembrane protein 70
Description	This gene likely encodes a mitochondrial membrane protein. The encoded protein may play a role in biogenesis of mitochondrial ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM70 is a nuclear‐encoded, inner mitochondrial membrane protein that plays a critical role in the biogenesis of ATP synthase in higher eukaryotes. Its deficiency, caused by mutations identified through comprehensive genetic and functional studies, leads to an isolated complex V deficiency that manifests clinically as neonatal encephalomyopathy, lactic acidosis, hypertrophic cardiomyopathy, muscular hypotonia, facial dysmorphism, and metabolic crises. These findings, reported in multiple studies, have established TMEM70 mutations as one of the most common causes of nuclear‐encoded ATP synthase deficiency, with clinical cases often showing a distinctive phenotype and severe metabolic derangements."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations have revealed that TMEM70 functions as an ancillary assembly factor that facilitates the proper incorporation and stabilization of ATP synthase subunits, particularly by mediating the formation of the c‐ring in the Fo domain. Biochemical studies demonstrate that TMEM70 is initially synthesized as a 29 kDa precursor, processed to a mature 21 kDa protein, and localizes predominantly to the inner mitochondrial membrane—specifically at cristae—where it appears to form oligomeric structures. Its absence or mutation disrupts the normal assembly cascade of ATP synthase, resulting in the accumulation of assembly intermediates, abnormal cristae morphology, and compensatory increases in other respiratory chain complexes. These mechanistic insights underscore its pivotal role during the assembly process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther studies employing advanced imaging, immunoprecipitation, and complexome profiling techniques have expanded our understanding of TMEM70’s role in mitochondrial ATP synthase assembly. These investigations indicate that TMEM70 oligomers interact directly with unassembled subunit c, providing a scaffold for the gradual formation of the c‐ring, and may also interact with additional proteins involved in the assembly of other oxidative phosphorylation complexes. Evolutionary analyses have placed TMEM70 in a family that includes TMEM186 and TMEM223, with its presence correlating with the existence of functional OXPHOS systems—a finding that further corroborates its essential role in mitochondrial bioenergetics. Collectively, these mechanistic and structural insights not only elucidate the assembly process of ATP synthase but also explain the diverse mitochondrial abnormalities associated with TMEM70 deficiency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alena Cízková, Viktor Stránecký, Johannes A Mayr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.246"}], "href": "https://doi.org/10.1038/ng.246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18953340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18953340"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomás Honzík, Markéta Tesarová, Johannes A Mayr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Dis Child (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/adc.2009.168096"}], "href": "https://doi.org/10.1136/adc.2009.168096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20335238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20335238"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ronen Spiegel, Morad Khayat, Stavit A Shalev, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Compensatory upregulation of respiratory chain complexes III and IV in isolated deficiency of ATP synthase due to TMEM70 mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2012.03.004"}], "href": "https://doi.org/10.1016/j.bbabio.2012.03.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22433607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22433607"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Michela Catteruccia, Daniela Verrigni, Diego Martinelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2014.01.001"}], "href": "https://doi.org/10.1016/j.ymgme.2014.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24485043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24485043"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Alessandra Torraco, Daniela Verrigni, Teresa Rizza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM70: a mutational hot spot in nuclear ATP synthase deficiency with a pivotal role in complex V biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-012-0343-8"}], "href": "https://doi.org/10.1007/s10048-012-0343-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22986587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22986587"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Kateřina Hejzlarová, Markéta Tesařová, Alena Vrbacká-Čížková, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and processing of the TMEM70 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2010.10.005"}], "href": "https://doi.org/10.1016/j.bbabio.2010.10.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20937241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20937241"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Joe Carroll, Jiuya He, Shujing Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2100558118"}], "href": "https://doi.org/10.1073/pnas.2100558118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33753518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33753518"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Hana Kratochvílová, Kateřina Hejzlarová, Marek Vrbacký, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial membrane assembly of TMEM70 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2014.02.010"}], "href": "https://doi.org/10.1016/j.mito.2014.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24576557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24576557"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Lifeng Wang, Lei Zuo, Jing Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual LQT1 and HCM phenotypes associated with tetrad heterozygous mutations in KCNQ1, MYH7, MYLK2, and TMEM70 genes in a three-generation Chinese family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Europace (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/europace/euv043"}], "href": "https://doi.org/10.1093/europace/euv043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25825456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25825456"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Anne K Braczynski, Stefan Vlaho, Klaus Müller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/462592"}], "href": "https://doi.org/10.1155/2015/462592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26550569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26550569"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Hela Bahri, Jeremie Buratto, Manuel Rojo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM70 forms oligomeric scaffolds within mitochondrial cristae promoting in situ assembly of mammalian ATP synthase proton channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2020.118942"}], "href": "https://doi.org/10.1016/j.bbamcr.2020.118942"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33359711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33359711"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Orna Staretz-Chacham, Ohad Wormser, Esther Manor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM70 deficiency: Novel mutation and hypercitrullinemia during metabolic decompensation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61138"}], "href": "https://doi.org/10.1002/ajmg.a.61138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30950220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30950220"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Anwar Baban, Rachele Adorisio, Bernadette Corica, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: A potential pitfall for the diagnosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61383"}], "href": "https://doi.org/10.1002/ajmg.a.61383"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31729175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31729175"}]}]}]}
Synonyms	MC5DN2
Proteins	TMM70_HUMAN
NCBI Gene ID	54968
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TMEM70 has 5,953 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 114 datasets.

Click the + buttons to view associations for TMEM70 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TMEM70 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 TMEM70 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TMEM70 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 TMEM70 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TMEM70 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TMEM70 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 TMEM70 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TMEM70 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 TMEM70 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 TMEM70 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TMEM70 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of TMEM70 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing TMEM70 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TMEM70 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TMEM70 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TMEM70 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TMEM70 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TMEM70 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TMEM70 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 TMEM70 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TMEM70 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 TMEM70 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 TMEM70 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 TMEM70 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TMEM70 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 TMEM70 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 TMEM70 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TMEM70 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 TMEM70 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.