XPC

Chr 3AR

XPC complex subunit, DNA damage recognition and repair factor

Also known as: RAD4, XP3, XPCC, p125

NCBI Gene: 7508ENSG00000154767UniProt: Q01831

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]

Primary Disease Associations & Inheritance

Xeroderma pigmentosum, group CMIM #278720
AR
Xeroderma pigmentosum, group CMIM #278720
AR
1191
ClinVar variants
68
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— XPC
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 61 VUS of 1191 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.000
Z-score 2.70
OE 0.56 (0.40–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.91 (0.85–0.99)
483 obs / 527.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.40–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.85–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 24 / 43.2Missense obs/exp: 483 / 527.9Syn Z: 0.13

ClinVar Variant Classifications

1191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic31
VUS61
Likely Benign250
Benign5
Conflicting1
37
Pathogenic
31
Likely Pathogenic
61
VUS
250
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
0
17
0
37
Likely Pathogenic
25
0
6
0
31
VUS
0
59
2
0
61
Likely Benign
0
6
134
110
250
Benign
0
0
5
0
5
Conflicting
—1
Total4565164110385

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XPC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

XPC-related xeroderma pigmentosum

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinCancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Xeroderma pigmentosum, group C

MIM #278720

Molecular basis of disorder known

Autosomal recessive

Xeroderma pigmentosum, group C

MIM #278720

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.
Kobaisi F et al.·Cell Death Dis
2024
Generation and characterization of CRISPR-Cas9-mediated XPC gene knockout in human skin cells.
Nasrallah A et al.·Sci Rep
2024
New pathogenic germline variants identified in mesothelioma.
Belcaid L et al.·Lung Cancer
2023Review
Germline variants in CDKN2A wild-type melanoma prone families.
Iversen GT et al.·Mol Oncol
2025
XPC Polymorphism and Risk for Lung Cancer in North Indian Patients Treated with Platinum Based Chemotherapy and Its Association with Clinical Outcomes.
Lawania S et al.·Pathol Oncol Res
2018Cohort
DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.
Kuricova M et al.·Toxicol Appl Pharmacol
2005Review
Xeroderma Pigmentosum: A Genetic Condition Skin Cancer Correlated-A Systematic Review.
Brambullo T et al.·Biomed Res Int
2022Review
XPC as breast cancer susceptibility gene: evidence from genetic profiling, statistical inferences and protein structural analysis.
Malik SS et al.·Breast Cancer
2020
Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms.
Riechelmann RP et al.·Endocr Relat Cancer
2023Cohort
Systematic Review and Meta-Analysis of the Influence of Genetic Variation on Ototoxicity in Platinum-Based Chemotherapy.
Hong DZ et al.·Otolaryngol Head Neck Surg
2023Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Xeroderma pigmentosum with multiple skin carcinoma and a homogenous XPC mutation: A case report from China and literature review.
Gao F et al.·J Int Med Res
2026🔓 Open AccessReview
A retrospective Case-Control study investigating the association of XPC Lys939Gln (rs2228001), XPD Lys751Gln (rs13181), and TP53 Arg72Pro (rs1042522) with papillary thyroid carcinoma susceptibility in the Bangladeshi population.
Jahan Bristy N et al.·Mol Biol Rep
2025
The deubiquitinase OTUD1 orchestrates cisplatin chemosensitivity of non-small cell lung cancer through destabilizing RAD23B/XPC.
Wu Z et al.·Oncogene
2025
XPC Deficiency Activate Cisplatin-Mediated Autophagy in Bladder Cancer by Limiting Novel PHRF1-Mediated Ubiquitination of the p53 Protein.
Zhao B et al.·Adv Sci (Weinh)
2026🔓 Open Access
[Clinical characterization and genetic analysis of a patient with Xeroderma pigmentosum in conjunct with basal cell carcinoma and melanoma due to variants of XPC gene].
Chang Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
UVB Phototherapy BurnInsulin-like Growth Factor 1Aging

Gene Expression Changes In Young and Geriatric Skin

RECRUITING
NCT03932162Phase EARLY_PHASE1Wright State UniversityStarted 2019-09-06
Insulin-Like Growth Factor 1No Insulin-Lie Growth Factor 1

External Resources

Links to major genomics databases and tools