DDB2

Chr 11AR

damage specific DNA binding protein 2

Also known as: DDBB, UV-DDB2, XPE

NCBI Gene: 1643ENSG00000134574UniProt: Q92466

This gene encodes a protein that is necessary for the repair of ultraviolet light-damaged DNA. This protein is the smaller subunit of a heterodimeric protein complex that participates in nucleotide excision repair, and this complex mediates the ubiquitylation of histones H3 and H4, which facilitates the cellular response to DNA damage. This subunit appears to be required for DNA binding. Mutations in this gene cause xeroderma pigmentosum complementation group E, a recessive disease that is characterized by an increased sensitivity to UV light and a high predisposition for skin cancer development, in some cases accompanied by neurological abnormalities. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Xeroderma pigmentosum, group E, DDB-negative subtypeMIM #278740
AR
185
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DDB2
🧬
Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group E · 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.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 73 VUS of 185 total submissions

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.
0.85LOEUF
pLI 0.000
Z-score 2.11
OE 0.52 (0.33–0.85)
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.
1.22Z-score
OE missense 0.78 (0.69–0.88)
187 obs / 240.1 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.0.52 (0.33–0.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.69–0.88)
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.0.94
0≤1.21.6
LoF obs/exp: 12 / 22.9Missense obs/exp: 187 / 240.1Syn Z: 0.50

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic8
VUS73
Likely Benign45
Benign26
Conflicting11
22
Pathogenic
8
Likely Pathogenic
73
VUS
45
Likely Benign
26
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
19
0
22
Likely Pathogenic
5
1
2
0
8
VUS
1
50
18
4
73
Likely Benign
0
5
19
21
45
Benign
0
0
25
1
26
Conflicting
—11
Total7588326185

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

View in ClinVar →

Protein Context — Lollipop Plot

DDB2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DDB2-related xeroderma pigmentosum, group E, ddb-negative subtype

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinCancer
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Xeroderma pigmentosum, group E, DDB-negative subtype

MIM #278740

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DDB2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Emerging Roles of DDB2 in Cancer.
Gilson P et al.·Int J Mol Sci
2019Review
Xeroderma pigmentosum group E and DDB2, a smaller subunit of damage-specific DNA binding protein: proposed classification of xeroderma pigmentosum, Cockayne syndrome, and ultraviolet-sensitive syndrome.
Itoh T·J Dermatol Sci
2006Review
Systematic identification of pathogenic variants of non-small cell lung cancer in the promoters of DNA-damage repair genes.
An M et al.·EBioMedicine
2024
Identification of a novel DDB2 mutation in a Chinese Han family with Xeroderma pigmentosum group E:a case report and literature review.
Yang R et al.·BMC Med Genet
2020Review
LINC01320 facilitates cell proliferation and migration of ovarian cancer via regulating PURB/DDB2/NEDD4L/TGF-β axis.
Wang G et al.·Sci Rep
2024
EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair.
Koyen AE et al.·Oncogene
2020
Hypoxia-inducible CircPFKFB4 Promotes Breast Cancer Progression by Facilitating the CRL4(DDB2) E3 Ubiquitin Ligase-mediated p27 Degradation.
Chen H et al.·Int J Biol Sci
2022
Single-molecule analysis of DNA-binding proteins from nuclear extracts (SMADNE).
Schaich MA et al.·Nucleic Acids Res
2023
DDB2 suppresses epithelial-to-mesenchymal transition in colon cancer.
Roy N et al.·Cancer Res
2013
Brazilian XP-E siblings carrying a novel DDB2 variant developed early-onset melanoma: a case report.
de Souza Timoteo AR et al.·BMC Med Genomics
2023Case report
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools