ERCC6

Chr 10ARADSomatic

ERCC excision repair 6, chromatin remodeling factor

Also known as: ARMD5, CKN2, COFS, COFS1, CSB, CSB-PGBD3, POF11, RAD26

This gene encodes a DNA-binding protein essential for transcription-coupled nucleotide excision repair and chromatin remodeling, with DNA-dependent ATPase activity that removes DNA lesions and regulates double-strand break repair. Mutations cause autosomal recessive Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1, both early-onset multisystem disorders with neurodegeneration, growth failure, and photosensitivity. The protein is critical for neuronal differentiation and has very low tolerance for loss-of-function mutations (LOEUF 0.802).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/AD/SomaticLOEUF 0.807 OMIM phenotypes
Clinical SummaryERCC6
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Gene-Disease Validity (ClinGen)
Cockayne spectrum with or without cerebrooculofacioskeletal syndrome · 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
0.80LOEUF
pLI 0.000
Z-score 2.96
OE 0.63 (0.490.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.10Z-score
OE missense 0.99 (0.931.05)
772 obs / 779.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.490.80)
00.351.4
Missense OE0.99 (0.931.05)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 46 / 73.3Missense obs/exp: 772 / 779.7Syn Z: -0.85
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveERCC6-related Cockayne syndromeLOFAR

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

DN
0.6550th %ile
GOF
0.4085th %ile
LOF
0.3744th %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

ERCC6 · 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.

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Clinical Literature
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