Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

ERCC6

ERCC excision repair 6, chromatin remodeling factor

The ERCC6 gene provides instructions for producing the Cockayne syndrome B (CSB) protein, crucial for DNA repair and accurate gene transcription. The ERCC6 gene is vital for cellular health, encoding a protein that helps fix damaged DNA, particularly within active genes.

Chromosome 10q11.23 Autosomal recessive HGNC:3438 Tier C
ERCC6 10q11.23 p arm q arm 10

ERCC6 is located on the long (q) arm of chromosome 10, at band 10q11.23. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 10 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
ERCC6 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ERCC6 gene, also known as ERCC excision repair 6, chromatin remodelling factor, plays a key role in maintaining genomic integrity. It produces a protein called Cockayne syndrome B (CSB), which is essential for DNA repair, particularly in actively transcribed genes. Dysfunctions in ERCC6 are associated with inherited conditions that affect various bodily systems.

What the gene does

The ERCC6 gene directs the synthesis of the Cockayne syndrome B (CSB) protein, which participates in repairing damaged DNA and facilitating gene transcription, the initial step in protein synthesis. DNA damage can arise from various sources, including UV radiation, toxic chemicals, and free radicals. While cells typically repair DNA damage effectively, the CSB protein is specifically involved in repairing damaged DNA within genes that are actively undergoing transcription. When damage occurs in these active genes, the RNA polymerase enzyme, which performs transcription, can become stalled. Research indicates that the CSB protein aids in dislodging RNA polymerase from these damaged sites, allowing the DNA to be repaired. Following repair, the CSB protein may also help restart the transcription process.

Video: Genetics 101

Chromosome location

The ERCC6 gene is located on chromosome 10, specifically at position 10q11.23. This chromosomal address indicates its precise position on the long arm of chromosome 10.

Protein structure

The ERCC6 protein consists of 1061 amino acids. It contains several disordered regions, including one at amino acids 1-39, another from 287-323, a third spanning 344-466, a fourth from 494-521, and a fifth from 537-573. These disordered regions may contribute to the protein's flexibility and its ability to interact with various molecular partners.

Key variants

Variations within the ERCC6 gene can alter the function of the Cockayne syndrome B (CSB) protein, potentially affecting its role in DNA repair and gene transcription. These genetic changes can range from single base alterations to larger deletions or duplications. The nature and location of the variant often dictate its impact on protein function and the resulting clinical presentation.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for ERCC6.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1033A>T
single nucleotide variant
 p.Lys345Ter Pathogenic ★★☆☆ Cockayne spectrum with or without cerebrooculofacioskeletal syndrome
c.1040del
Deletion
 p.Gly347fs Pathogenic/Likely pathogenic ★★☆☆ Cockayne syndrome type 2
c.1066G>T
single nucleotide variant
 p.Glu356Ter Pathogenic/Likely pathogenic ★★☆☆ ERCC6-related disorder
c.1100_1101del
Microsatellite
 p.Asp366_Ser367insTer Pathogenic ★★☆☆ DE SANCTIS-CACCHIONE SYNDROME
c.1431_1432del
Microsatellite
 p.Lys478fs Pathogenic ★★☆☆ Cockayne syndrome
c.145del
Deletion
 p.Ser49fs Pathogenic ★★☆☆ Cockayne spectrum with or without cerebrooculofacioskeletal syndrome
c.1717_1720del
Microsatellite
 p.Cys573fs Pathogenic/Likely pathogenic ★★☆☆ Cerebrooculofacioskeletal syndrome 1
c.1738C>T
single nucleotide variant
 p.Gln580Ter Pathogenic/Likely pathogenic ★★☆☆ Cerebrooculofacioskeletal syndrome 1
c.1894C>T
single nucleotide variant
 p.Gln632Ter Pathogenic ★★☆☆ Cockayne spectrum with or without cerebrooculofacioskeletal syndrome
c.255del
Deletion
 p.Ser86fs Pathogenic ★★☆☆ Cockayne spectrum with or without cerebrooculofacioskeletal syndrome

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ERCC6 gene are primarily associated with Cockayne syndrome, an inherited condition typically passed down in an autosomal recessive manner. Cockayne syndrome can manifest with symptoms such as abnormally small head size (microcephaly), very slow growth, developmental delays, and heightened sensitivity to sunlight. Over 60 different ERCC6 gene variants have been identified as causes of Cockayne syndrome.

Inheritance pattern

Conditions caused by pathogenic ERCC6 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous ERCC6 carrier status across ancestry groups?

UK clinical status

The ERCC6 gene is recognised within the NHS Genomic Medicine Service, featuring on several UK national genomic testing panels. These include panels for Arthrogryposis (R83), Bilateral congenital or childhood onset cataracts (R31), Foetal anomalies (R21), Hereditary neuropathy or pain disorder (R78), Retinal disorders (R32), Severe microcephaly (R88), and Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome (R227). It is also listed on the DDG2P panel, for conditions like Inherited white matter disorders, Intellectual disability, and IUGR and IGF abnormalities.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Arthrogryposis · R83 NHS GMS → Bilateral congenital or childhood onset cataracts · R31 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Retinal disorders · R32 NHS GMS → Severe microcephaly · R88 NHS GMS → Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome · R227 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the ERCC6 gene?

The ERCC6 gene provides instructions for the Cockayne syndrome B (CSB) protein, which is crucial for repairing damaged DNA, particularly within active genes, and assisting in the process of gene transcription.

What conditions are associated with ERCC6 gene variants?

Variants in the ERCC6 gene are primarily linked to Cockayne syndrome. This is an inherited condition characterised by symptoms such as microcephaly, slow growth, developmental delay, and increased sensitivity to sunlight.

How is Cockayne syndrome inherited?

Cockayne syndrome, caused by ERCC6 gene variants, is typically inherited in an autosomal recessive pattern. This means an individual must inherit two altered copies of the gene, one from each parent, to develop the condition.

References

  1. Wilson BT, Lochan A, Stark Z. Novel missense mutations in a conserved loop between ERCC6 (CSB) helicase motifs V and VI: Insights into Cockayne syndrome. American journal of medical genetics. Part A. 2016. PMID: 26749132
  2. Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. Mechanisms of ageing and development. 2013. PMID: 23428416
  3. Vélez-Cruz R, Egly JM. Cockayne syndrome group B (CSB) protein: at the crossroads of transcriptional networks. Mechanisms of ageing and development. 2013. PMID: 23562425
  4. Laugel V, Dalloz C, Durand M. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Human mutation. 2010. PMID: 19894250
  5. Spivak G, Hanawalt PC. Host cell reactivation of plasmids containing oxidative DNA lesions is defective in Cockayne syndrome but normal in UV-sensitive syndrome fibroblasts. DNA repair. 2006. PMID: 16129663
  6. Newman JC, Bailey AD, Weiner AM. Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling. Proceedings of the National Academy of Sciences of the United States of America. 2006. PMID: 16772382
  7. Horibata K, Iwamoto Y, Kuraoka I. Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome. Proceedings of the National Academy of Sciences of the United States of America. 2004. PMID: 15486090
  8. Licht CL, Stevnsner T, Bohr VA. Cockayne syndrome group B cellular and biochemical functions. American journal of human genetics. 2003. PMID: 14639525
  9. Adam MP, Bick S, Mirzaa GM. Cockayne Syndrome. 1993. PMID: 20301516
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .