ERCC4

Chr 16AR

ERCC excision repair 4, endonuclease catalytic subunit

Also known as: ERCC11, FANCQ, RAD1, XFEPS, XPF

The protein functions as a catalytic component of a structure-specific DNA repair endonuclease that makes 5-prime incisions essential for nucleotide excision repair and interstrand cross-link repair. Mutations cause autosomal recessive conditions including xeroderma pigmentosum group F, Fanconi anemia complementation group Q, Cockayne syndrome overlap disorders, and XFE progeroid syndrome, affecting DNA repair mechanisms that protect against UV damage and other genotoxic stresses. The gene shows very low constraint against loss-of-function variants, which is consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.904 OMIM phenotypes
Clinical SummaryERCC4
🧬
Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group F · 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.
📖
GeneReview available — ERCC4
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
0.90LOEUF
pLI 0.000
Z-score 2.07
OE 0.64 (0.470.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.76Z-score
OE missense 1.10 (1.021.18)
557 obs / 508.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.64 (0.470.90)
00.351.4
Missense OE1.10 (1.021.18)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 25 / 39.0Missense obs/exp: 557 / 508.6Syn Z: -1.58
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongERCC4-related Fanconi anemiaLOFAR
definitiveERCC4-related xeroderma pigmentosum, group FLOFAR

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

DN
0.6356th %ile
GOF
0.3689th %ile
LOF
0.3259th %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

ERCC4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →