TIMM50 Gene

HGNC Family	Phosphatases
Name	translocase of inner mitochondrial membrane 50 homolog (S. cerevisiae)
Description	This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex. The encoded protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This protein may also play a role in maintaining the membrane permeability barrier, and knockdown of this gene in human cells results in the release of cytochrome c and apoptosis. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTIMM50 is a key component of the mitochondrial inner membrane import machinery, acting as the major receptor of the TIM23 complex to mediate the translocation of presequence‐containing proteins into the mitochondrial matrix. In human cells, TIMM50 not only facilitates protein import but also possesses phosphatase activity that contributes to the maintenance of mitochondrial membrane potential, proper assembly of oxidative phosphorylation complexes, and overall mitochondrial structural integrity. Defects or mutations in TIMM50 have been shown to lead to mitochondrial dysfunction, including aberrant cristae organization, reduced respiratory capacity, and increased reactive oxygen species production, which are associated with severe neurological deficits and complex V deficiencies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classic role in mitochondrial protein import, TIMM50 transiently interacts with key steroidogenic enzymes at the inner membrane, thereby regulating steroid hormone biosynthesis. Its association with 3β‐hydroxysteroid dehydrogenase type 2 and with the cytochrome P450 side‐chain cleavage enzyme is critical for inducing the necessary conformational changes that facilitate their enzymatic activities, underscoring a novel regulatory role for TIMM50 in steroidogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTIMM50 is also emerging as an important factor in pathological conditions, including cancer and cardiac hypertrophy. In several cancers such as breast cancer and non‐small cell lung carcinoma, TIMM50 expression is upregulated—either via mutant forms of p53 that transcriptionally activate its promoter or through other oncogenic mechanisms—thereby promoting cell proliferation, invasion, and chemoresistance by modulating downstream signaling pathways like ERK/P90RSK. In addition, alterations in its expression have been linked to impaired mitochondrial membrane potential, increased apoptosis, and changes in oxidative stress responses in cardiac tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yin Guo, NaEun Cheong, ZhiJia Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M402049200"}], "href": "https://doi.org/10.1074/jbc.M402049200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15044455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15044455"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M A Shahrour, O Staretz-Chacham, D Dayan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.12855"}], "href": "https://doi.org/10.1111/cge.12855"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27573165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27573165"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Aurelio Reyes, Laura Melchionda, Alberto Burlina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/emmm.201708698"}], "href": "https://doi.org/10.15252/emmm.201708698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30190335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30190335"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Frederic Tort, Olatz Ugarteburu, Laura Texidó, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23779"}], "href": "https://doi.org/10.1002/humu.23779"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31058414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31058414"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yongqiang Zhang, Yun Xu, Qing Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and structural characterization of human translocase of inner membrane of mitochondria Tim50."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Expr Purif (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pep.2011.06.012"}], "href": "https://doi.org/10.1016/j.pep.2011.06.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21742040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21742040"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yongqiang Zhang, Honghua Deng, Xinzheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of divalent metal ions with human translocase of inner membrane of mitochondria Tim50."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.10.060"}], "href": "https://doi.org/10.1016/j.bbrc.2012.10.060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23098911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23098911"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kevin J Pawlak, Manoj Prasad, James L Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.290031"}], "href": "https://doi.org/10.1074/jbc.M111.290031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21930695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21930695"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Himangshu S Bose, Fadi Gebrail, Brendan Marshall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00484-18"}], "href": "https://doi.org/10.1128/MCB.00484-18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30348838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30348838"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Heidi Sankala, Catherine Vaughan, Jing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of the mitochondrial transport protein, Tim50, by mutant p53 contributes to cell growth and chemoresistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2011.05.005"}], "href": "https://doi.org/10.1016/j.abb.2011.05.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21621504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21621504"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shui-Ping Gao, He-Fen Sun, Hong-Lin Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of TIM50 suppresses proliferation and induces apoptosis in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3878-0"}], "href": "https://doi.org/10.1007/s13277-015-3878-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26289846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26289846"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kai Tang, Yifan Zhao, Hailing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of Pathological Cardiac Hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Heart Assoc (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/JAHA.116.004346"}], "href": "https://doi.org/10.1161/JAHA.116.004346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28432072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28432072"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xiupeng Zhang, Shuai Han, Haijing Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non-small cell lung cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22969"}], "href": "https://doi.org/10.1002/mc.22969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30604908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30604908"}]}]}]}
Synonyms	TIM50, TIM50L, MGCA9
Proteins	TIM50_HUMAN
NCBI Gene ID	92609
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TIMM50 has 8,093 functional associations with biological entities spanning 9 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, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for TIMM50 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TIMM50 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 TIMM50 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TIMM50 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 TIMM50 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TIMM50 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 TIMM50 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 TIMM50 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing TIMM50 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 TIMM50 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TIMM50 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TIMM50 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TIMM50 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 TIMM50 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 TIMM50 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 TIMM50 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing TIMM50 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of TIMM50 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TIMM50 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TIMM50 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TIMM50 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TIMM50 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TIMM50 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 TIMM50 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 TIMM50 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TIMM50 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 TIMM50 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 TIMM50 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TIMM50 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 TIMM50 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.