ERCC2

Chr 19AR

ERCC excision repair 2, TFIIH core complex helicase subunit

Also known as: COFS2, CXPD, EM9, TFIIH, TTD, TTD1, XPD

The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Primary Disease Associations & Inheritance

?Cerebrooculofacioskeletal syndrome 2MIM #610756
AR
Trichothiodystrophy 1, photosensitiveMIM #601675
AR
Xeroderma pigmentosum, group DMIM #278730
AR
UniProtCerebro-oculo-facio-skeletal syndrome 2
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical SummaryERCC2
🧬
Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group D · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

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.
1.09LOEUF
pLI 0.000
Z-score 1.10
OE 0.82 (0.621.09)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.38Z-score
OE missense 0.95 (0.881.03)
454 obs / 477.4 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.0.82 (0.621.09)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.881.03)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
01.21.6
LoF obs/exp: 34 / 41.7Missense obs/exp: 454 / 477.4Syn Z: -2.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ERCC2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ERCC2-related cerebrooculofacioskeletal syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

ERCC2-related trichothiodystrophy photosensitive

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

ERCC2-related xeroderma pigmentosum, group D

definitive
ARLoss Of FunctionAbsent Gene Product
Cancer
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

?Cerebrooculofacioskeletal syndrome 2

MIM #610756

Molecular basis of disorder known

Autosomal recessive

Trichothiodystrophy 1, photosensitive

MIM #601675

Molecular basis of disorder known

Autosomal recessive

Xeroderma pigmentosum, group D

MIM #278730

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ERCC2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association Studies of ERCC2 rs13181 Polymorphism with Pancreatic Cancer Susceptibility.
Shao T et al.·Crit Rev Eukaryot Gene Expr
2021Meta-analysis
Top 10 resultsSearch PubMed ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →