ERCC6 Gene

Name	excision repair cross-complementation group 6
Description	This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ERCC6, also known as Cockayne syndrome B (CSB), is a multifunctional protein that plays a central role in transcription‐coupled nucleotide excision repair (TC‐NER) as well as in the regulation of transcription and chromatin dynamics. In its canonical role, ERCC6 monitors RNA polymerase II and is rapidly recruited to sites of DNA damage—especially UV‐induced lesions—to facilitate repair of transcription‐blocking adducts. This function is tightly regulated by post‐translational modifications and protein–protein interactions. For example, ERCC6 is stabilized at damaged sites through the action of UVSSA, which recruits the deubiquitinating enzyme USP7, thereby securing its assembly into active TC‐NER complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " The ATPase activity of ERCC6 is essential to overcome autoinhibition and drive chromatin remodeling at lesion‐stalled transcription complexes, ensuring efficient repair and resumption of transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, its intrinsic ubiquitin‐binding domain is required for triggering the damage incision step during TC‐NER."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond TC‐NER, ERCC6 is pivotal for maintaining genomic stability. Mutations in ERCC6 are causative for Cockayne syndrome, a multisystem disorder characterized by neurological defects, growth failure, photosensitivity, and features of premature aging."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Recent work has also implicated ERCC6 in additional pathways such as double‐strand break repair—where it interacts with factors like RIF1 to mediate chromatin remodeling at damage sites"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "—and in mitochondrial transcription, highlighting its broader role in safeguarding cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ERCC6/CSB is a master regulator in the repair of transcription‐blocking DNA lesions, functioning by coordinating the assembly and activity of TC‐NER complexes through ATP‐driven chromatin remodeling and ubiquitin‐regulated stabilization. Its diverse roles in DNA repair, transcription regulation, and even mitochondrial gene expression underscore its critical importance in the maintenance of genome integrity and cellular function.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Petra Schwertman, Anna Lagarou, Dick H W Dekkers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2230"}], "href": "https://doi.org/10.1038/ng.2230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22466611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22466611"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xue Zhang, Katsuyoshi Horibata, Masafumi Saijo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2228"}], "href": "https://doi.org/10.1038/ng.2228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22466612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22466612"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Luca Proietti-De-Santis, Pascal Drané, Jean-Marc Egly "}, {"type": "b", "children": [{"type": "t", "text": "Cockayne syndrome B protein regulates the transcriptional program after UV irradiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601071"}], "href": "https://doi.org/10.1038/sj.emboj.7601071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16601682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16601682"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Vincent van den Boom, Elisabetta Citterio, Deborah Hoogstraten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA damage stabilizes interaction of CSB with the transcription elongation machinery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200401056"}], "href": "https://doi.org/10.1083/jcb.200401056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15226310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15226310"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Roy Anindya, Pierre-Olivier Mari, Ulrik Kristensen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.04.017"}], "href": "https://doi.org/10.1016/j.molcel.2010.04.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20541997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20541997"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "V Laugel, C Dalloz, M Durand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21154"}], "href": "https://doi.org/10.1002/humu.21154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19894250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19894250"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nicole L Batenburg, John R Walker, Sylvie M Noordermeer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-02114-x"}], "href": "https://doi.org/10.1038/s41467-017-02114-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29203878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29203878"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Brian R Berquist, Chandrika Canugovi, Peter Sykora, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gks565"}], "href": "https://doi.org/10.1093/nar/gks565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22743267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22743267"}]}]}]}
Synonyms	UVSS1, CKN2, RAD26, COFS, COFS1, ARMD5, POF11
Proteins	ERCC6_HUMAN
NCBI Gene ID	2074
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ERCC6 has 7,261 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 124 datasets.

Click the + buttons to view associations for ERCC6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ERCC6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ERCC6 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ERCC6 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 ERCC6 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 ERCC6 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 ERCC6 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 ERCC6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ERCC6 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 ERCC6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ERCC6 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 ERCC6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ERCC6 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ERCC6 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 ERCC6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ERCC6 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 ERCC6 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 ERCC6 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with ERCC6 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing ERCC6 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 ERCC6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ERCC6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ERCC6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ERCC6 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 ERCC6 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 ERCC6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ERCC6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ERCC6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ERCC6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ERCC6 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 ERCC6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ERCC6 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ERCC6 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ERCC6 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 ERCC6 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 ERCC6 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 ERCC6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ERCC6 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 ERCC6 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 ERCC6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ERCC6 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 ERCC6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.