XPC Gene: Xeroderma Pigmentosum Complementation Group C
Key player in global genome nucleotide excision repair (GG-NER) and UV-induced DNA damage recognition
Gene Information Card
| Symbol | XPC |
|---|---|
| Full Name | XPC complex subunit, DNA damage recognition and repair factor |
| Gene Type | Protein coding |
| Chromosomal Location | 3p25.1 |
| NCBI Gene ID | 7508 ncbi.nlm.nih.gov/gene/7508 |
| Ensembl ID | ENSG00000154767 |
| UniProt ID | Q01831 |
| OMIM ID | 613208 |
| HGNC ID | 12816 |
| Aliases | XPCC, RAD4, p125 |
Description
The XPC gene encodes a component of the XPC-RAD23B-CETN2 complex, which is essential for global genome nucleotide excision repair (GG-NER). This complex recognizes bulky DNA adducts, such as those induced by ultraviolet (UV) light, and initiates the repair process. Mutations in XPC cause xeroderma pigmentosum complementation group C (XP-C), a disorder characterized by extreme UV sensitivity, high risk of skin cancers, and neurological abnormalities in some cases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Xeroderma Pigmentosum, Group C (XP-C) | Loss-of-function mutations in XPC impair GG-NER, leading to accumulation of UV-induced DNA photoproducts and increased mutagenesis. | OMIM #278720; ClinVar pathogenic variants |
| Cutaneous Malignant Melanoma | Defective XPC-mediated repair increases UV-induced mutation burden, predisposing to melanoma. | COSMIC; NCBI GeneRIF |
| Basal Cell Carcinoma | Impaired DNA damage recognition in XPC-deficient cells promotes UV-driven skin carcinogenesis. | OMIM; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 6.8 | Medium |
| Lung | 5.2 | Medium |
| Testis | 4.1 | Low |
| Brain | 2.3 | Low |
| Liver | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 7.1 | UV-responsive; used in NER studies |
| HeLa | 6.5 | Cervical cancer; moderate expression |
| A549 | 5.8 | Lung carcinoma |
| HEK293 | 4.9 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1643_1644delTG (p.Val548Alafs*25) | Frameshift | Common in XP-C patients | Loss of function |
| c.2251C>T (p.Arg751*) | Nonsense | Reported in XP-C | Loss of function |
| c.1243C>T (p.Arg415*) | Nonsense | Found in European XP-C | Loss of function |
| c.1735C>T (p.Arg579*) | Nonsense | Associated with severe XP-C | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most XPC mutations are loss-of-function, leading to truncated or unstable protein that cannot form the XPC-RAD23B complex, abolishing GG-NER.
Gain of Function (GOF)
Not reported for XPC.
Dominant Negative (DN)
Not reported; XP-C is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • damaged DNA binding (GO:0003684) | • mismatch repair (GO:0006298) |
| • nucleotide-excision repair (GO:0006289) | • protein binding (GO:0005515) |
| • nucleus (GO:0005634) |
Pathways
• Nucleotide excision repair (hsa03420)
• Global genome nucleotide excision repair (GG-NER)
• p53 signaling pathway (hsa04115) – indirect via DNA damage response
Protein Summary
The XPC protein (125 kDa) is a key sensor of helix-distorting DNA lesions. It forms a stable complex with RAD23B and CETN2, which recognizes UV-induced cyclobutane pyrimidine dimers and 6-4 photoproducts. XPC recruits TFIIH and other NER factors to initiate repair. The protein contains a transglutaminase-like domain and a beta-hairpin domain critical for DNA binding. Loss of XPC function leads to the cancer-prone disorder xeroderma pigmentosum group C.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| XPC Knockout HEK293 Cell Line | EDJ-KQ16162 | Human | 7508 | Details Get a Quote |
| XPC Knockout A-549 Cell Line | EDJ-KQ47354 | Human | 7508 | Details Get a Quote |
| XPC Knockout HCT 116 Cell Line | EDJ-KQ47355 | Human | 7508 | Details Get a Quote |
| XPC Knockout HeLa Cell Line | EDJ-KQ47356 | Human | 7508 | Details Get a Quote |
| XPC (p.Q939K) Point Mutation in HAP1 Cell Line | EDC03387 | Human | 7508 | Details Get a Quote |
| XPC (p.A627=) Point Mutation in HAP1 Cell Line | EDC03392 | Human | 7508 | Details Get a Quote |
| XPC (p.A499V) Point Mutation in HAP1 Cell Line | EDC03393 | Human | 7508 | Details Get a Quote |
| XPC (c.2604+90G>T )Point Mutation in HAP1 Cell Line | EDC03388 | Human | 7508 | Details Get a Quote |
| XPC (c.2604+28C>G )Point Mutation in HAP1 Cell Line | EDC03389 | Human | 7508 | Details Get a Quote |
| XPC (c.2514+68T>C )Point Mutation in HAP1 Cell Line | EDC03390 | Human | 7508 | Details Get a Quote |
| XPC (c.2251-6A>C )Point Mutation in HAP1 Cell Line | EDC03391 | Human | 7508 | Details Get a Quote |
| XPC (c.-27G>C )Point Mutation in HAP1 Cell Line | EDC03394 | Human | 7508 | Details Get a Quote |
