TMEM126A Gene

Name	transmembrane protein 126A
Description	The protein encoded by this gene is a mitochondrial membrane protein of unknown function. Defects in this gene are a cause of optic atrophy type 7 (OPA7). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM126A is an evolutionarily conserved mitochondrial transmembrane protein that has emerged as a crucial factor in nonsyndromic autosomal‐recessive optic neuropathies. Multiple studies in consanguineous families—including those from North Africa as well as unrelated populations—have identified pathogenic variants in TMEM126A associated with optic atrophy and, in some cases, auditory neuropathy. The high expression of TMEM126A in retinal compartments enriched in mitochondria underscores its importance in maintaining retinal ganglion cell function and preserving optic nerve integrity."}, {"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": "\nBeyond its role in neuro-ophthalmic disorders, TMEM126A plays a critical part in mitochondrial bioenergetics through its involvement in the assembly of complex I of the respiratory chain. Mechanistic studies have demonstrated that TMEM126A interacts with the newly synthesized ND4 subunit and remains associated with the ND4 distal membrane module during complex I disassembly, thereby ensuring proper complex assembly and function. Notably, its function in complex I biogenesis is distinct from that of the related protein TMEM126B, which targets a different module, underscoring a specific and nonredundant role for TMEM126A in mitochondrial maintenance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, TMEM126A has been implicated in cancer biology, where its reduced expression is associated with enhanced metastatic potential in breast cancer. Downregulation of TMEM126A leads to mitochondrial dysfunction marked by increased reactive oxygen species production and loss of mitochondrial membrane potential. These mitochondrial alterations contribute to extracellular matrix remodeling and the induction of an epithelial-to-mesenchymal transition, thereby promoting tumor metastasis. Thus, TMEM126A not only serves as a key factor in mitochondrial homeostasis but also emerges as a novel suppressor of metastasis and a potential prognostic indicator in oncology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sylvain Hanein, Isabelle Perrault, Olivier Roche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.03.003"}], "href": "https://doi.org/10.1016/j.ajhg.2009.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19327736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19327736"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Esther Meyer, Michel Michaelides, Louise J Tee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2010)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20405026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20405026"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Julie Désir, Frauke Coppieters, Nicole Van Regemorter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM126A mutation in a Moroccan family with autosomal recessive optic atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2012)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22815638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22815638"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sylvain Hanein, Mathilde Garcia, Lucas Fares-Taie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM126A is a mitochondrial located mRNA (MLR) protein of the mitochondrial inner membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2013.02.025"}], "href": "https://doi.org/10.1016/j.bbagen.2013.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23500070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23500070"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Katja Kloth, Matthis Synofzik, Christoph Kernstock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel likely pathogenic variants in TMEM126A identified in non-syndromic autosomal recessive optic atrophy: two case reports."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-019-0795-x"}], "href": "https://doi.org/10.1186/s12881-019-0795-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30961538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30961538"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Luigi D'Angelo, Elisa Astro, Monica De Luise, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109002"}], "href": "https://doi.org/10.1016/j.celrep.2021.109002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33882309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33882309"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Luke E Formosa, Boris Reljic, Alice J Sharpe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Optic atrophy-associated TMEM126A is an assembly factor for the ND4-module of mitochondrial 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.2019665118"}], "href": "https://doi.org/10.1073/pnas.2019665118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33879611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33879611"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "He-Fen Sun, Xue-Li Yang, Yang Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of TMEM126A promotes extracellular matrix remodeling, epithelial-to-mesenchymal transition, and breast cancer metastasis by regulating mitochondrial retrograde signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2018.10.018"}], "href": "https://doi.org/10.1016/j.canlet.2018.10.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30393159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30393159"}]}]}]}
Synonyms	OPA7
Proteins	T126A_HUMAN
NCBI Gene ID	84233
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TMEM126A has 4,890 functional associations with biological entities spanning 8 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) extracted from 104 datasets.

Click the + buttons to view associations for TMEM126A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TMEM126A 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 TMEM126A 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 TMEM126A 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 TMEM126A 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 TMEM126A 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 TMEM126A 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 TMEM126A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TMEM126A 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 TMEM126A 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 TMEM126A 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 TMEM126A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TMEM126A 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 TMEM126A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TMEM126A 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 TMEM126A 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 TMEM126A gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TMEM126A gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of TMEM126A gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TMEM126A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TMEM126A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TMEM126A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TMEM126A 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 TMEM126A 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 TMEM126A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TMEM126A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TMEM126A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TMEM126A 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 TMEM126A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TMEM126A 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 TMEM126A 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 TMEM126A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TMEM126A 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 TMEM126A 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 TMEM126A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TMEM126A 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 TMEM126A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TMEM126A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TMEM126A 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 TMEM126A from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TMEM126A gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of TMEM126A gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.