CCDC22 Gene

Name	coiled-coil domain containing 22
Description	This gene encodes a protein containing a coiled-coil domain. The encoded protein functions in the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) by interacting with COMMD (copper metabolism Murr1 domain-containing) proteins. The mouse orthologous protein has been shown to bind copines, which are calcium-dependent, membrane-binding proteins that may function in calcium signaling. This human gene has been identified as a novel candidate gene for syndromic X-linked intellectual disability. [provided by RefSeq, Aug 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCDC22 is emerging as a critical component of a conserved multiprotein “commander” or CCC complex that orchestrates endosomal cargo sorting and recycling. As part of the CCC complex—which also includes CCDC93 and COMMD family proteins—CCDC22 helps facilitate the retrieval of membrane proteins from endosomes, thereby preventing their lysosomal degradation and ensuring proper recycling to the cell surface."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " \n In support of this role, disruption of CCDC22 within the complex leads to defects in the endosomal trafficking of critical cargoes including the copper transporter ATP7A and the low‐density lipoprotein receptor, resulting in disturbances in copper and cholesterol homeostasis.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond trafficking, CCDC22 has been implicated in the regulation of NF‐κB signaling. Binding of various COMMD proteins to CCDC22 appears to be essential for directing the ubiquitination and turnover of IκB proteins, a process critical for appropriate NF‐κB activation. Mutations or reduced expression of CCDC22 lead to impaired IκB degradation and attenuated NF‐κB signaling, which may contribute to developmental anomalies and immunologic dysregulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic studies further underscore the physiological importance of CCDC22. Hypomorphic and missense variants in CCDC22 are associated with an X‐linked syndrome that overlaps with Ritscher–Schinzel syndrome, characterized by intellectual disability, craniofacial, and cardiac malformations, as well as with predisposition to certain autoimmune conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " These findings indicate that proper CCDC22 function is essential not only for endosomal sorting but also for the regulation of signaling pathways that impact development and immune homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kerrie E McNally, Rebecca Faulkner, Florian Steinberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3610"}], "href": "https://doi.org/10.1038/ncb3610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28892079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28892079"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christine A Phillips-Krawczak, Amika Singla, Petro Starokadomskyy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E14-06-1073"}], "href": "https://doi.org/10.1091/mbc.E14-06-1073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25355947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25355947"}]}, {"type": "r", "ref": 3, "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": 4, "children": [{"type": "t", "text": "Benjamin J Liebeskind, Richard W Aldrich, Edward M Marcotte "}, {"type": "b", "children": [{"type": "t", "text": "Ancestral reconstruction of protein interaction networks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Comput Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pcbi.1007396"}], "href": "https://doi.org/10.1371/journal.pcbi.1007396"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31658251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31658251"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Petro Starokadomskyy, Nathan Gluck, Haiying Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI66466"}], "href": "https://doi.org/10.1172/JCI66466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23563313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23563313"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mateusz Kolanczyk, Peter Krawitz, Jochen Hecht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2014.109"}], "href": "https://doi.org/10.1038/ejhg.2014.109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24916641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24916641"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Cathrine E Gjerulfsen, Rikke S Møller, Christina D Fenger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expansion of the CCDC22 associated Ritscher-Schinzel/3C syndrome and review of the literature: Should the minimal diagnostic criteria be revised?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2021.104246"}], "href": "https://doi.org/10.1016/j.ejmg.2021.104246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34020006"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34020006"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Fabio D'Amico, Evangelia Skarmoutsou, Lauren J Lo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases with focus on systemic lupus erythematosus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.imlet.2016.11.011"}], "href": "https://doi.org/10.1016/j.imlet.2016.11.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27888057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27888057"}]}]}]}
Synonyms	JM1, RTSC2, CXORF37
Proteins	CCD22_HUMAN
NCBI Gene ID	28952
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CCDC22 has 5,492 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 107 datasets.

Click the + buttons to view associations for CCDC22 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 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 CCDC22 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CCDC22 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 CCDC22 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CCDC22 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CCDC22 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 CCDC22 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CCDC22 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 CCDC22 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 CCDC22 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CCDC22 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CCDC22 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 CCDC22 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CCDC22 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CCDC22 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CCDC22 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 CCDC22 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 CCDC22 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CCDC22 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CCDC22 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CCDC22 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CCDC22 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CCDC22 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 CCDC22 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 CCDC22 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CCDC22 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 CCDC22 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 CCDC22 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CCDC22 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GAD Gene-Disease Associations	diseases associated with CCDC22 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 CCDC22 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CCDC22 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.