TMEM127 Gene

Name	transmembrane protein 127
Description	This gene encodes a transmembrane protein with four predicted transmembrane domains. The protein is associated with a subpopulation of vesicular organelles corresponding to early endosomal structures, with the Golgi, and with lysosomes, and may participate in protein trafficking between these structures. Mutations in this gene and several other genes cause pheochromocytomas. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2022]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM127 was first identified as a novel tumor suppressor gene implicated in pheochromocytoma and paraganglioma. Germline mutations in TMEM127 are found in both familial and apparently sporadic cases, where loss of the wild‐type allele leads to enhanced signaling through key cellular pathways such as mTOR. These initial studies established TMEM127’s role in controlling cell growth and proliferation, with mutant tumors showing hyperphosphorylation of mTOR effector proteins and a transcriptional profile overlapping that of NF1 mutations. Such associations have been observed across diverse cohorts, supporting its participation in adrenal tumorigenesis as well as a broader spectrum of neoplasms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations have revealed that TMEM127 localizes dynamically to components of the endomembrane system and lysosomes, where it interacts with the Rag GTPases, the ragulator (LAMTOR) complex, and the vATPase—key elements in amino acid–mediated mTORC1 activation. Under nutrient-rich conditions, TMEM127 reduces mTORC1 recruitment to Rags, thereby restraining mTOR signaling. In addition, TMEM127 has been shown to influence receptor tyrosine kinase regulation, notably by binding to RET and recruiting the NEDD4 E3 ubiquitin ligase via its C-terminal PxxY motifs to promote RET ubiquitination and lysosome-mediated degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical tumor suppressor functions and regulation of mTOR signaling, TMEM127 also contributes to the modulation of immune processes and cancer predisposition beyond the adrenal gland. In an infection model involving the Salmonella effector SteD, TMEM127 cooperates with the HECT E3 ubiquitin ligase WWP2 to promote the ubiquitination of mature MHC class II molecules, thereby diminishing antigen presentation. Moreover, germline TMEM127 mutations have been detected in cases of renal cell carcinoma accompanied by pheochromocytoma, and rare instances of homozygous mutations have been described, further expanding the phenotypic spectrum associated with TMEM127 dysfunction. These findings underscore its multifaceted roles in cellular homeostasis, tumor suppression, and clinical diagnosis of hereditary neoplasms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuejuan Qin, Li Yao, Elizabeth E King, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutations in TMEM127 confer susceptibility to pheochromocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.533"}], "href": "https://doi.org/10.1038/ng.533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20154675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20154675"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Li Yao, Francesca Schiavi, Alberto Cascon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jama.2010.1830"}], "href": "https://doi.org/10.1001/jama.2010.1830"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21156949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21156949"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shoulei Jiang, Patricia L M Dahia "}, {"type": "b", "children": [{"type": "t", "text": "Minireview: the busy road to pheochromocytomas and paragangliomas has a new member, TMEM127."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2011-0052"}], "href": "https://doi.org/10.1210/en.2011-0052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21447639"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21447639"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hartmut P H Neumann, Maren Sullivan, Aurelia Winter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutations of the TMEM127 gene in patients with paraganglioma of head and neck and extraadrenal abdominal sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2011-0114"}], "href": "https://doi.org/10.1210/jc.2011-0114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21613359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21613359"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "M S Elston, G Y Meyer-Rochow, D Prosser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutation in the TMEM127 gene associated with phaeochromocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Intern Med J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/imj.12088"}], "href": "https://doi.org/10.1111/imj.12088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23551308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23551308"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M Yu Yukina, E A Troshina, D G Beltsevich "}, {"type": "b", "children": [{"type": "t", "text": "[Hereditary pheochromocytoma-associated syndromes. Part 1]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ter Arkh (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.17116/terarkh2015879102-105"}], "href": "https://doi.org/10.17116/terarkh2015879102-105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26591561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26591561"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Attila Patócs, Nikoletta K Lendvai, Henriett Butz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12253-016-0050-0"}], "href": "https://doi.org/10.1007/s12253-016-0050-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26960314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26960314"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Birke Bausch, Francesca Schiavi, Ying Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaoncol.2017.0223"}], "href": "https://doi.org/10.1001/jamaoncol.2017.0223"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28384794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28384794"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yilun Deng, Yuejuan Qin, Subramanya Srikantan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddy095"}], "href": "https://doi.org/10.1093/hmg/ddy095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29547888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29547888"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Qianjin Guo, Zi-Ming Cheng, Hector Gonzalez-Cantú, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2023.113070"}], "href": "https://doi.org/10.1016/j.celrep.2023.113070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37659079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37659079"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Karen Gomez Hernandez, Shereen Ezzat, Chantal F Morel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virchows Arch (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00428-015-1755-2"}], "href": "https://doi.org/10.1007/s00428-015-1755-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25800244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25800244"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "K Eijkelenkamp, M J W Olderode-Berends, R B van der Luijt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous TMEM127 mutations in 2 patients with bilateral pheochromocytomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13202"}], "href": "https://doi.org/10.1111/cge.13202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29282712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29282712"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Eric Alix, Camilla Godlee, Ondrej Cerny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2020.04.024"}], "href": "https://doi.org/10.1016/j.chom.2020.04.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32526160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32526160"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Shahida K Flores, Yilun Deng, Ziming Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/clinem/dgaa396"}], "href": "https://doi.org/10.1210/clinem/dgaa396"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32575117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32575117"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Gustavo Armaiz-Pena, Shahida K Flores, Zi-Ming Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/clinem/dgaa741"}], "href": "https://doi.org/10.1210/clinem/dgaa741"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33051659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33051659"}]}]}]}
Proteins	TM127_HUMAN
NCBI Gene ID	55654
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TMEM127 has 6,858 functional associations with biological entities spanning 7 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA) extracted from 112 datasets.

Click the + buttons to view associations for TMEM127 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 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 TMEM127 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TMEM127 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 TMEM127 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TMEM127 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 TMEM127 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TMEM127 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 TMEM127 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 TMEM127 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TMEM127 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of TMEM127 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TMEM127 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TMEM127 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TMEM127 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TMEM127 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 TMEM127 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 TMEM127 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TMEM127 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TMEM127 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TMEM127 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TMEM127 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TMEM127 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TMEM127 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 TMEM127 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 TMEM127 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TMEM127 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 TMEM127 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 TMEM127 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TMEM127 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 TMEM127 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TMEM127 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 TMEM127 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.