XPC

Chr 3AR

XPC complex subunit, DNA damage recognition and repair factor

Also known as: RAD4, XP3, XPCC, p125

The XPC protein functions as a damage-sensing and DNA-binding component of the XPC complex, which initiates global genome nucleotide excision repair by recognizing DNA helix distortions and recruiting downstream repair machinery. Mutations cause xeroderma pigmentosum group C, an autosomal recessive disorder characterized by extreme UV sensitivity and early-onset skin cancers due to impaired DNA repair. The gene is highly constrained against loss-of-function variants (LOEUF 0.78), reflecting the critical importance of DNA repair mechanisms.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.782 OMIM phenotypes
Clinical SummaryXPC
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Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group C · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 48 VUS of 200 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — XPC
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.70
OE 0.56 (0.400.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.69Z-score
OE missense 0.91 (0.850.99)
483 obs / 527.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.400.78)
00.351.4
Missense OE0.91 (0.850.99)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 24 / 43.2Missense obs/exp: 483 / 527.9Syn Z: 0.13

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic7
VUS48
Likely Benign103
Benign4
23
Pathogenic
7
Likely Pathogenic
48
VUS
103
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
0
3
0
23
Likely Pathogenic
7
0
0
0
7
VUS
0
47
1
0
48
Likely Benign
0
4
53
46
103
Benign
0
0
4
0
4
Total27516146185

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.

3D Protein StructureAlphaFold
Clinical Literature
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