XPA

Chr 9AR

XPA, DNA damage recognition and repair factor

Also known as: XP1, XPAC

This gene encodes a zinc finger protein that initiates DNA nucleotide excision repair by binding to damaged sites and serving as a scaffold to assemble the repair complex, particularly for UV-induced DNA damage. Mutations cause xeroderma pigmentosum group A, an autosomal recessive disorder characterized by extreme UV hypersensitivity and markedly increased skin cancer risk. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.97), reflecting its essential role in DNA repair.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.972 OMIM phenotypes
Clinical SummaryXPA
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Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group A · 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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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.65
OE 0.56 (0.340.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.35Z-score
OE missense 0.92 (0.801.06)
139 obs / 151.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.340.97)
00.351.4
Missense OE0.92 (0.801.06)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 9 / 16.2Missense obs/exp: 139 / 151.0Syn Z: -0.44
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveXPA-related xeroderma pigmentosumLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.6051th %ile
LOF
0.2871th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗