TMEM165 Gene

Name	transmembrane protein 165
Description	This gene encodes a predicted transmembrane protein with a perinuclear Golgi-like distribution in fibroblasts. Mutations in this gene are associated with the autosomal recessive disorder congenital disorder of glycosylation, type IIk. Knockdown of this gene's expression causes decreased sialylation in HEK cells and suggests this gene plays a role in terminal Golgi glycosylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM165 is a highly conserved, Golgi‐localized transmembrane protein belonging to the UPF0016 family that plays a critical role in protein glycosylation. Mutations in TMEM165 cause a form of congenital disorder of glycosylation (CDG) characterized by abnormal serum glycosylation profiles, skeletal dysplasia, and multisystem defects. A number of studies in both mammalian cells and yeast models have demonstrated that TMEM165 is essential for maintaining Golgi ion homeostasis—particularly the balance of manganese (Mn²⁺) and calcium (Ca²⁺) ions—which serve as key cofactors for numerous glycosyltransferases. Disruption of TMEM165 function leads to impaired Golgi manganese handling and subsequent glycosylation defects that can be rescued by Mn²⁺ supplementation. In addition, pathogenic missense and splice mutations in TMEM165 have been shown to affect its subcellular localization, stability, and ion transport activity, thereby supporting its proposed function as a Golgi‐resident Ca²⁺/Mn²⁺ antiporter."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established role in glycosylation, TMEM165 overexpression has been linked to enhanced invasive activity in hepatocellular carcinoma. Elevated TMEM165 expression in tumor tissues correlates with increased levels of matrix metalloproteinase‐12 (MMP‑12), suggesting that dysregulation of TMEM165 may contribute to cancer progression by modulating the cellular proteolytic environment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, detailed analyses of serum biomarkers—such as the characterization of bikunin isoforms—have provided additional insights into the molecular pathogenesis of TMEM165‐related CDG, opening promising avenues for noninvasive diagnosis and targeted therapeutic strategies including antisense oligonucleotide–mediated splicing rescue. Investigations in related UPF0016 family members, exemplified by studies on Samd3 expression in immune cell subsets, emphasize the broader importance of this protein family in regulating diverse aspects of cellular ion homeostasis and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "François Foulquier, Mustapha Amyere, Jaak Jaeken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM165 deficiency causes a congenital disorder of glycosylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.05.002"}], "href": "https://doi.org/10.1016/j.ajhg.2012.05.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22683087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22683087"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Didier Demaegd, François Foulquier, Anne-Sophie Colinet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Newly characterized Golgi-localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1219871110"}], "href": "https://doi.org/10.1073/pnas.1219871110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23569283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23569283"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Claire Rosnoblet, Dominique Legrand, Didier Demaegd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of disease-causing mutations on TMEM165 subcellular localization, a recently identified protein involved in CDG-II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt146"}], "href": "https://doi.org/10.1093/hmg/ddt146"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23575229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23575229"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "P Yuste-Checa, C Medrano, A Gámez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antisense-mediated therapeutic pseudoexon skipping in TMEM165-CDG."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.12402"}], "href": "https://doi.org/10.1111/cge.12402"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24720419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24720419"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sven Potelle, Willy Morelle, Eudoxie Dulary, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw026"}], "href": "https://doi.org/10.1093/hmg/ddw026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27008884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27008884"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Eudoxie Dulary, Sven Potelle, Dominique Legrand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM165 deficiencies in Congenital Disorders of Glycosylation type II (CDG-II): Clues and evidences for roles of the protein in Golgi functions and ion homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tice.2016.06.006"}], "href": "https://doi.org/10.1016/j.tice.2016.06.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27401145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27401145"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marie-Ange Krzewinski-Recchi, Sven Potelle, Anne-Marie Mir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for splice transcript variants of TMEM165, a gene involved in CDG."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gen Subj (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2017.01.011"}], "href": "https://doi.org/10.1016/j.bbagen.2017.01.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28088503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28088503"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sven Potelle, Eudoxie Dulary, Leslie Climer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Manganese-induced turnover of TMEM165."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20160910"}], "href": "https://doi.org/10.1042/BCJ20160910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28270545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28270545"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Elodie Lebredonchel, Marine Houdou, Sven Potelle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dissection of TMEM165 function in Golgi glycosylation and its Mn"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " sensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochimie (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biochi.2019.07.016"}], "href": "https://doi.org/10.1016/j.biochi.2019.07.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31351090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31351090"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dorothée Vicogne, Marine Houdou, Anne Garat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jimd.12161"}], "href": "https://doi.org/10.1002/jimd.12161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31415112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31415112"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Elodie Lebredonchel, Marine Houdou, Hans-Heinrich Hoffmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigating the functional link between TMEM165 and SPCA1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20190488"}], "href": "https://doi.org/10.1042/BCJ20190488"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31652305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31652305"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jiri Stribny, Louise Thines, Antoine Deschamps, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human Golgi protein TMEM165 transports calcium and manganese in yeast and bacterial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.012249"}], "href": "https://doi.org/10.1074/jbc.RA119.012249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32047108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32047108"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Dorothée Vicogne, Nicolas Beauval, Zoé Durin, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "TMEM165, a Golgi transmembrane protein, is a novel marker for hepatocellular carcinoma and its depletion impairs invasion activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6565"}], "href": "https://doi.org/10.3892/or.2018.6565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30015898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30015898"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Walid Haouari, Johanne Dubail, Samra Lounis-Ouaras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum bikunin isoforms in congenital disorders of glycosylation and linkeropathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jimd.12291"}], "href": "https://doi.org/10.1002/jimd.12291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32700771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32700771"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Annika E Peters, Konrad Knöpper, Anika Grafen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A multifunctional mouse model to study the role of Samd3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.202149469"}], "href": "https://doi.org/10.1002/eji.202149469"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34626120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34626120"}]}]}]}
Synonyms	TPARL, FT27, TMPT27, GDT1, CDG2K
Proteins	TM165_HUMAN
NCBI Gene ID	55858
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TMEM165 has 5,851 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for TMEM165 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TMEM165 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 TMEM165 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 TMEM165 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TMEM165 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 TMEM165 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TMEM165 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 TMEM165 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 TMEM165 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TMEM165 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TMEM165 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TMEM165 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 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 TMEM165 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TMEM165 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TMEM165 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TMEM165 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 TMEM165 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving TMEM165 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TMEM165 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TMEM165 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TMEM165 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 TMEM165 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 TMEM165 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TMEM165 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 TMEM165 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 TMEM165 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TMEM165 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 TMEM165 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TMEM165 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TMEM165 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.