TIMM44 Gene

Name	translocase of inner mitochondrial membrane 44 homolog (yeast)
Description	This gene encodes a peripheral membrane protein associated with the mitochondrial inner membrane translocase, which functions in the import of proteins across the mitochondrial inner membrane and into the mitochondrial matrix. The encoded protein mediates binding of mitochondrial heat shock protein 70 to the translocase of inner mitochondrial membrane 23 (TIM23) complex. Expression of this gene is upregulated in kidney in a mouse model of diabetes. A mutation in this gene is associated with familial oncocytic thyroid carcinoma. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTIMM44 is a critical component of the mitochondrial protein import machinery. Predominantly located in the inner mitochondrial membrane, TIMM44 anchors mitochondrial heat‐shock protein 70 (mtHsp70) to the TIM23 complex, thereby facilitating the import of nucleus-encoded preproteins into the mitochondrial matrix. This essential function is tightly linked to the maintenance of mitochondrial integrity and ATP production, as evidenced by its upregulation in diabetic kidneys where proper protein import is vital for cellular metabolism and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its housekeeping role, TIMM44 has emerged as an important factor in cancer biology. In ovarian cancer, the RNA-binding protein HuR stabilizes TIMM44 mRNA via its 3′UTR, promoting enhanced cellular proliferation; conversely, TIMM44 depletion in ovarian cancer cells hinders cell growth, underscoring its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In glioma, elevated levels of TIMM44, driven in part by transcriptional activation via GATA3 in a YME1L-dependent manner, correlate with increased cell viability, proliferation, migration, and resistance to mitochondrial dysfunction, all of which contribute to poor overall patient survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in bladder cancer, TIMM44 overexpression is associated with hyperactivation of the Akt-mTOR pathway, and pharmacological blockade of TIMM44 using agents like MB-10 disrupts mitochondrial membrane potential, reduces ATP production, induces oxidative stress, and ultimately promotes apoptosis and cell cycle arrest."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in tumor cell survival, TIMM44 is essential for angiogenesis. In endothelial cells, proper function of TIMM44 supports mitochondrial protein import, thereby ensuring adequate ATP production and the mitigation of oxidative stress. Experimental silencing or pharmacological inhibition of TIMM44 in various endothelial cell models leads to mitochondrial depolarization, increased reactive oxygen species generation, apoptosis, and impaired capillary tube formation. These findings highlight TIMM44 as a promising target for therapeutic intervention in diseases characterized by abnormal angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yu Wang, Akihiro Katayama, Takahiro Terami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2015.02.004"}], "href": "https://doi.org/10.1016/j.metabol.2015.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25749183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25749183"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaohui Yu, Yujiao Li, Yumei Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biochem Biophys (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12013-020-00939-w"}], "href": "https://doi.org/10.1007/s12013-020-00939-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32901414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32901414"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yi-Zhuo Guo, Gang Chen, Man Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMM44 is a potential therapeutic target of human glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.78616"}], "href": "https://doi.org/10.7150/thno.78616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36438483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36438483"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lifeng Zhang, Xiaokai Shi, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A first-in-class TIMM44 blocker inhibits bladder cancer cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-024-06585-x"}], "href": "https://doi.org/10.1038/s41419-024-06585-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38467612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38467612"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhou-Rui Ma, Hong-Peng Li, Shi-Zhong Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mitochondrial protein TIMM44 is required for angiogenesis in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-05826-9"}], "href": "https://doi.org/10.1038/s41419-023-05826-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37147302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37147302"}]}]}]}
Synonyms	TIM44
Proteins	TIM44_HUMAN
NCBI Gene ID	10469
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TIMM44 has 6,654 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 115 datasets.

Click the + buttons to view associations for TIMM44 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TIMM44 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 TIMM44 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TIMM44 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 TIMM44 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TIMM44 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 TIMM44 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 TIMM44 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TIMM44 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TIMM44 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TIMM44 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 TIMM44 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 TIMM44 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 TIMM44 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing TIMM44 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TIMM44 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TIMM44 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TIMM44 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TIMM44 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 TIMM44 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 TIMM44 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TIMM44 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 TIMM44 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 TIMM44 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TIMM44 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 TIMM44 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TIMM44 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 TIMM44 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TIMM44 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 TIMM44 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TIMM44 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.