TMEM126B Gene

HGNC Family	Mitochondrial respiratory chain complex assembly factors
Name	transmembrane protein 126B
Description	This gene encodes a mitochondrial transmembrane protein which is a component of the mitochondrial complex I assembly complex. The encoded protein serves as an assembly factor that is required for formation of the membrane arm of the complex. It interacts with NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 13. Naturally occurring mutations in this gene are associated with isolated complex I deficiency. A pseudogene of this gene has been defined on chromosome 9. [provided by RefSeq, Apr 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM126B encodes a mitochondrial complex I assembly factor that plays a critical role in the proper formation of the enzyme’s membrane arm. Genetic studies have revealed that pathogenic variants in TMEM126B disrupt complex I assembly, leading to significant deficiencies in mitochondrial respiration. In patients carrying compound‐heterozygous or homozygous mutations, these defects manifest clinically as exercise‐induced myalgia, exercise intolerance, and myopathy, ultimately reflecting the broad phenotypic spectrum of mitochondrial disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nAdaptation to cellular stress also involves modulation of TMEM126B abundance. Under chronic hypoxic conditions, hypoxia‐inducible factor 1α (HIF‑1α) triggers a proteolytic cascade that selectively degrades TMEM126B via the action of the E3-ubiquitin ligase β-TrCP1. This HIF‑dependent reduction in TMEM126B contributes to impaired complex I assembly, suggesting that controlled attenuation of its function may be an adaptive response to sustained oxygen deprivation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n\nFurthermore, expanded mutation analyses have linked splicing and insertion mutations of TMEM126B to severe mitochondrial phenotypes, including Leigh and Leigh-like syndromes. Aberrant splicing events lead to exon skipping and premature translational termination, which in turn cause marked defects in complex I content and assembly; these findings broaden both the mutational and clinical spectra associated with TMEM126B‐related disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laura Sánchez-Caballero, Benedetta Ruzzenente, Lucas Bianchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.05.022"}], "href": "https://doi.org/10.1016/j.ajhg.2016.05.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27374773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27374773"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Charlotte L Alston, Alison G Compton, Luke E Formosa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.05.021"}], "href": "https://doi.org/10.1016/j.ajhg.2016.05.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27374774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27374774"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dominik C Fuhrmann, Ilka Wittig, Stefan Dröse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-018-2779-y"}], "href": "https://doi.org/10.1007/s00018-018-2779-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29464284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29464284"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiyue Zhou, Xiaoting Lou, Yuwei Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel biallelic mutations in TMEM126B cause splicing defects and lead to Leigh-like syndrome with severe complex I deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-022-01102-4"}], "href": "https://doi.org/10.1038/s10038-022-01102-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36482121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36482121"}]}]}]}
Synonyms	HT007
Proteins	T126B_HUMAN
NCBI Gene ID	55863
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TMEM126B has 5,815 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 104 datasets.

Click the + buttons to view associations for TMEM126B from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of TMEM126B gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TMEM126B 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 TMEM126B gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TMEM126B 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 TMEM126B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TMEM126B 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 TMEM126B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TMEM126B gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing TMEM126B protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TMEM126B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TMEM126B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B 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 TMEM126B gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TMEM126B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TMEM126B gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TMEM126B 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 TMEM126B gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TMEM126B gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with TMEM126B 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 TMEM126B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TMEM126B 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 TMEM126B 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 TMEM126B gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TMEM126B 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 TMEM126B from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TMEM126B gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TMEM126B gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing TMEM126B from the GeneSigDB Published Gene Signatures dataset.