ERCC3

Chr 2AR

ERCC excision repair 3, TFIIH core complex helicase subunit

Also known as: BTF2, GTF2H, RAD25, Ssl2, TFIIH, TTD2, XPB

This gene encodes an ATP-dependent DNA helicase that is essential for both nucleotide excision repair and RNA polymerase II transcription as a core component of the TFIIH complex. Mutations cause autosomal recessive disorders including xeroderma pigmentosum group B and photosensitive trichothiodystrophy, both characterized by extreme photosensitivity, developmental abnormalities, and increased cancer risk. The gene is highly intolerant to loss-of-function variants (pLI near 0, LOEUF 0.79), reflecting its essential cellular functions.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.792 OMIM phenotypes
Clinical SummaryERCC3
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Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group B · 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
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GeneReview available — ERCC3
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
0.79LOEUF
pLI 0.000
Z-score 2.68
OE 0.56 (0.400.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.93Z-score
OE missense 0.87 (0.800.95)
379 obs / 433.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.400.79)
00.351.4
Missense OE0.87 (0.800.95)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 24 / 43.0Missense obs/exp: 379 / 433.6Syn Z: 0.33
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveERCC3-related xeroderma pigmentosum, group BLOFAR
definitiveERCC3-related trichothiodystrophy photosensitiveLOFAR

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

DN
0.7036th %ile
GOF
0.4282th %ile
LOF
0.3940th %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

ERCC3 · 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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