COMMD9 Gene

Name	COMM domain containing 9
Description	Predicted to be involved in sodium ion transport. Predicted to act upstream of or within cholesterol homeostasis. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COMMD9 is a member of the evolutionarily conserved COMMD protein family that contributes to multiple aspects of endosomal trafficking by operating as a component of the COMMD/CCDC22/CCDC93 (CCC) complex. In the liver, COMMD9 participates in the recycling of key transmembrane proteins—as exemplified by its role in ensuring proper localization of the low‐density lipoprotein receptor (LDLR) and the copper transporter ATP7B—thereby influencing cholesterol and copper homeostasis; indeed, hepatic deficiency of COMMD9 perturbs LDLR recycling and leads to increased plasma LDL cholesterol, while loss of COMMD9 (along with other COMMD proteins) destabilizes the CCC complex and results in hepatic copper accumulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In renal collecting duct cells, COMMD9, together with COMMD3, regulates sodium reabsorption by reducing epithelial sodium channel (ENaC) cell surface expression, thereby acting as an endogenous modulator of Na⁺ transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, COMMD9 has emerged as a cargo‐specific regulator in endosomal sorting, as it, in conjunction with COMMD5, modulates Notch receptor recycling; loss of COMMD9 leads to Notch accumulation in intracellular compartments, and its deletion causes embryonic lethality along with complex cardiovascular defects that mimic Notch insufficiency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition to these homeostatic roles, COMMD9 is implicated in human disease states; it is up‐regulated in non‐small cell lung cancer where it interacts with TFDP1 to promote activation of the TFDP1/E2F1 pathway, enhancing cell proliferation and migration, and its gene amplification is observed in subsets of head and neck squamous cell carcinomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Structural studies further indicate that COMMD9, like other COMMD proteins, forms obligatory dimers through its conserved C-terminal COMM domain, which is critical for interactions within the CCC complex and for non-specific membrane association."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted roles of COMMD9 in governing receptor recycling, ion homeostasis, and cell signaling, and they highlight its potential as a therapeutic target in metabolic and proliferative diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paulina Bartuzi, Daniel D Billadeau, Robert Favier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10961"}], "href": "https://doi.org/10.1038/ncomms10961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26965651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26965651"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amika Singla, Qing Chen, Kohei Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of murine copper homeostasis by members of the COMMD protein family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Model Mech (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dmm.045963"}], "href": "https://doi.org/10.1242/dmm.045963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33262129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33262129"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Adam W Ware, Tanya T Cheung, Sahib Rasulov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epithelial Na"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Channel: Reciprocal Control by COMMD10 and Nedd4-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fphys.2018.00793"}], "href": "https://doi.org/10.3389/fphys.2018.00793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29997525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29997525"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong Feng Liu, Marianne Swart, Ying Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00158.2013"}], "href": "https://doi.org/10.1152/ajprenal.00158.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23637203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23637203"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haiying Li, Yeon Koo, Xicheng Mao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201505108"}], "href": "https://doi.org/10.1083/jcb.201505108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26553930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26553930"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Weihua Zhan, Wenjuan Wang, Tianyu Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2016.11.016"}], "href": "https://doi.org/10.1016/j.cellsig.2016.11.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27871936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27871936"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anna-Kaarina Järvinen, Reija Autio, Sami Kilpinen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20551"}], "href": "https://doi.org/10.1002/gcc.20551"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18314910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18314910"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Michael D Healy, Manuela K Hospenthal, Ryan J Hall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into the architecture and membrane interactions of the conserved COMMD proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.35898"}], "href": "https://doi.org/10.7554/eLife.35898"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30067224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30067224"}]}]}]}
Synonyms	HSPC166, LINC00610
Proteins	COMD9_HUMAN
NCBI Gene ID	29099
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

COMMD9 has 5,425 functional associations with biological entities spanning 8 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) extracted from 109 datasets.

Click the + buttons to view associations for COMMD9 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of COMMD9 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 COMMD9 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with COMMD9 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with COMMD9 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of COMMD9 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of COMMD9 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 COMMD9 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of COMMD9 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing COMMD9 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 COMMD9 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing COMMD9 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing COMMD9 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 COMMD9 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 2025	cellular components co-occuring with COMMD9 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 COMMD9 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with COMMD9 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with COMMD9 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with COMMD9 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of COMMD9 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 COMMD9 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at COMMD9 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 COMMD9 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of COMMD9 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 COMMD9 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 COMMD9 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 COMMD9 from the GeneSigDB Published Gene Signatures dataset.