XPA

Chr 9AR

XPA, DNA damage recognition and repair factor

Also known as: XP1, XPAC

NCBI Gene: 7507ENSG00000136936UniProt: P23025

This gene encodes a zinc finger protein plays a central role in nucleotide excision repair (NER), a specialized type of DNA repair. NER is responsible for repair of UV radiation-induced photoproducts and DNA adducts induced by chemical carcinogens and chemotherapeutic drugs. The encoded protein interacts with DNA and several NER proteins, acting as a scaffold to assemble the NER incision complex at sites of DNA damage. Mutations in this gene cause Xeroderma pigmentosum complementation group A (XP-A), an autosomal recessive skin disorder featuring hypersensitivity to sunlight and increased risk for skin cancer. [provided by RefSeq, Aug 2017]

Primary Disease Associations & Inheritance

Xeroderma pigmentosum, group AMIM #278700
AR
Xeroderma pigmentosum, group AMIM #278700
AR
505
ClinVar variants
74
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— XPA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 Pathogenic / Likely Pathogenic· 116 VUS of 505 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.
0.97LOEUF
pLI 0.000
Z-score 1.65
OE 0.56 (0.34–0.97)
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.
0.35Z-score
OE missense 0.92 (0.80–1.06)
139 obs / 151.0 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 (0.34–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.80–1.06)
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.1.08
0≤1.21.6
LoF obs/exp: 9 / 16.2Missense obs/exp: 139 / 151.0Syn Z: -0.44

ClinVar Variant Classifications

505 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic26
VUS116
Likely Benign172
Benign9
Conflicting5
48
Pathogenic
26
Likely Pathogenic
116
VUS
172
Likely Benign
9
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
1
26
0
48
Likely Pathogenic
16
3
7
0
26
VUS
1
98
15
2
116
Likely Benign
0
2
61
109
172
Benign
0
0
9
0
9
Conflicting
—5
Total38104118111376

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

View in ClinVar →

Protein Context — Lollipop Plot

XPA · protein map & ClinVar variants

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

Gene2Phenotype Curations

XPA-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 A

MIM #278700

Molecular basis of disorder known

Autosomal recessive

Xeroderma pigmentosum, group A

MIM #278700

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP10/XAB2/ANXA2 axis promotes DNA damage repair to enhance chemoresistance to oxaliplatin in colorectal cancer.
Liu X et al.·J Exp Clin Cancer Res
2025
Xeroderma pigmentosum.
Lehmann AR et al.·Orphanet J Rare Dis
2011Review
DNA repair-deficient Xpa and Xpa/p53+/- knock-out mice: nature of the models.
van Steeg H et al.·Toxicol Pathol
2001Review
Xpa knockout mice.
de Vries A et al.·Semin Cancer Biol
1996Review
XPA: DNA Repair Protein of Significant Clinical Importance.
Borszéková Pulzová L et al.·Int J Mol Sci
2020Review
Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure.
Muniesa-Vargas A et al.·Nat Commun
2024
[Xeroderma pigmentosum].
Takeuchi S·Nihon Rinsho
2000Review
A diagnostic model for Parkinson's disease based on circadian rhythm-related genes.
Wang L et al.·J Transl Med
2024Functional
The RASSF1A tumor suppressor regulates XPA-mediated DNA repair.
Donninger H et al.·Mol Cell Biol
2015
[Xeroderma Pigmentosum].
Nishigori C·Brain Nerve
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Skin Cancer

DNA Repair Activity in the Skin of Day and Night Shift Workers

RECRUITING
NCT04122456Phase NAWright State UniversityStarted 2022-12-07
Ultraviolet B RadiationNo Ultraviolet B Radiation

External Resources

Links to major genomics databases and tools