XPC Gene

Name	xeroderma pigmentosum, complementation group C
Description	The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXPC is a pivotal sensor in global genome nucleotide excision repair (NER). It recognizes a broad spectrum of bulky, helix‐distorting DNA lesions—such as the (6–4) photoproducts generated by ultraviolet light—and is central to the initial damage‐recognition step. Recruitment of XPC is facilitated by accessory factors like UV‐damaged DNA binding protein (UV-DDB), which triggers reversible ubiquitylation of XPC and thereby modulates its DNA binding affinity and promotes the transfer of the lesion to the core repair machinery. Structural analyses have mapped critical domains within XPC, including an α-helical region that binds centrin 2, and have shown that its association with HR23B stabilizes XPC against proteasomal degradation and ensures proper damage recognition."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nXPC’s expression and activity are tightly regulated in response to DNA damage. Its transcription is induced in a p53-dependent manner—ensuring that the cell swiftly mobilizes repair capacity—and is further modulated by regulators such as SIRT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, post-translational modifications play critical roles in XPC function. For example, reversible ubiquitylation—mediated first by UV-DDB and further refined by the SUMO-targeted ubiquitin ligase RNF111—facilitates the timely release of XPC from damaged chromatin so that downstream factors can act, while deubiquitinating enzymes such as USP7 protect XPC from premature proteolysis. Moreover, the regulated nuclear-cytoplasmic shuttling of XPC further contributes to its optimal function during the DNA damage response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in NER, XPC also contributes to the repair of oxidative DNA damage. As part of the XPC–HR23B complex, it functions as a cofactor that stimulates base excision repair enzymes—enhancing activities of glycosylases such as OGG1 and thymine DNA glycosylase—to promote the removal of oxidative lesions and G/T mismatches."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " Structural insights, including crystallographic studies of centrin-2 bound to an XPC peptide, reveal the molecular interactions essential for this multifaceted activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In clinical contexts, mutations and aberrant splicing events in XPC—notably found in xeroderma pigmentosum patients—compromise its function and are associated with increased genomic instability and cancer susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kaoru Sugasawa, Yuki Okuda, Masafumi Saijo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.02.035"}], "href": "https://doi.org/10.1016/j.cell.2005.02.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15882621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15882621"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maureen E Fitch, Satoshi Nakajima, Akira Yasui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307254200"}], "href": "https://doi.org/10.1074/jbc.M307254200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12944386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12944386"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryotaro Nishi, Yuki Okuda, Eriko Watanabe, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-specific protease 7 regulates nucleotide excision repair through deubiquitinating XPC protein and preventing XPC protein from undergoing ultraviolet light-induced and VCP/p97 protein-regulated proteolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.589812"}], "href": "https://doi.org/10.1074/jbc.M114.589812"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25118285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25118285"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Karin Broberg, Jonas Björk, Karin Paulsson, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgi204"}], "href": "https://doi.org/10.1093/carcin/bgi204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16081512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16081512"}]}]}]}
Synonyms	XP3, XPCC, RAD4, p125
Proteins	XPC_HUMAN
NCBI Gene ID	7508
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

XPC has 8,885 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 136 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

XPC 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 XPC 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 XPC 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 XPC 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 XPC 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 XPC 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 XPC 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 XPC 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 XPC gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of XPC gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of XPC 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 XPC gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with XPC gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with XPC protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with XPC 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 XPC gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of XPC 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 XPC 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 XPC gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with XPC gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of XPC gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing XPC 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 XPC gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing XPC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing XPC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing XPC 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 XPC 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 XPC 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 XPC 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 XPC gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with XPC gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with XPC gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with XPC gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of XPC 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 XPC gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for XPC protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving XPC gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving XPC gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with XPC 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 XPC 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 XPC gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.