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ERCC3

ERCC excision repair 3, TFIIH core complex helicase subunit

The ERCC3 gene encodes the XPB protein, a key component of the TFIIH complex involved in gene transcription and essential DNA repair processes. ERCC3 plays a vital role in maintaining genomic integrity by participating in nucleotide excision repair (NER), a critical mechanism for fixing damaged DNA.

Chromosome 2q14.3 Autosomal recessive HGNC:3435 Tier C
ERCC3 2q14.3 p arm q arm 2

ERCC3 is located on the long (q) arm of chromosome 2, at band 2q14.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 2 in the library →

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Clinical tests that include this

Carrier Screening panel
ERCC3 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ERCC3 gene, also known as XPB, provides instructions for producing a protein that is an integral subunit of the general transcription factor IIH (TFIIH) complex. This complex has two main functions: regulating gene transcription and repairing damaged DNA. By contributing to these processes, ERCC3 is crucial for normal cellular function and protection against DNA damage from environmental factors.

What the gene does

The XPB protein, encoded by ERCC3, is an essential part of the TFIIH complex, which is involved in two critical cellular activities. Firstly, it participates in gene transcription, the initial step in protein production, thereby helping to regulate the activity of many genes. Secondly, the TFIIH complex, with the help of XPB, plays a significant role in DNA repair, particularly through the nucleotide excision repair (NER) pathway. In NER, the TFIIH complex unwinds sections of double-stranded DNA surrounding damage, with XPB thought to act as a wedge to hold the DNA strands apart, allowing other proteins to remove and replace the damaged segment.

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Chromosome location

The ERCC3 gene is located on chromosome 2 at position 2q14.3. This region of the human genome contains the genetic instructions for the ERCC3 protein, which comprises 782 amino acids.

Protein structure

The ERCC3 protein exhibits a complex domain architecture essential for its function. An N-terminal disordered region spans amino acids 1-51, followed by a nuclear localization signal motif from amino acids 6-18. Another disordered region is found between amino acids 218-241. Key functional components include the Helicase ATP-binding domain (amino acids 327-488) and the Helicase C-terminal domain (amino acids 542-702), which are crucial for its helicase activity. Within the ATP-binding domain, a DEVH box motif is located from amino acids 441-444.

Domain map · 782 amino acids
Nuclear localization signal (6–18)Helicase ATP-binding (327–488)DEVH box (441–444)Helicase C-terminal (542–702)Nuclear localization s6–18Helicase ATP-binding327–488Helicase C-terminal542–7021~391782
Motif - short conserved sequence
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:P19447Length:782 aaStructure:AlphaFold

Key variants

Variants within the ERCC3 gene can impact the function of the XPB protein, potentially affecting its role in DNA repair and gene transcription. These genetic changes can lead to altered protein activity, contributing to various inherited conditions.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for ERCC3.
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.1115_1120dup
Duplication
 p.Trp374Ter Pathogenic/Likely pathogenic ★★☆☆ Trichothiodystrophy 2, photosensitive
c.1162C>T
single nucleotide variant
 p.Gln388Ter Pathogenic/Likely pathogenic ★★☆☆ Trichothiodystrophy 2, photosensitive
c.1300G>T
single nucleotide variant
 p.Glu434Ter Pathogenic/Likely pathogenic ★★☆☆ Xeroderma pigmentosum group B
c.1354C>T
single nucleotide variant
 p.Arg452Ter Pathogenic/Likely pathogenic ★★☆☆ Xeroderma pigmentosum group B
c.1588C>T
single nucleotide variant
 p.Arg530Ter Pathogenic/Likely pathogenic ★★☆☆ Trichothiodystrophy 2, photosensitive
c.1720C>T
single nucleotide variant
 p.Arg574Ter Pathogenic/Likely pathogenic ★★☆☆ Trichothiodystrophy 2, photosensitive
c.1735del
Deletion
 p.Tyr579fs Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1757del
Deletion
 p.Gln586fs Pathogenic/Likely pathogenic ★★☆☆ Inborn genetic diseases
c.2131C>T
single nucleotide variant
 p.Gln711Ter Pathogenic/Likely pathogenic ★★☆☆ Inborn genetic diseases
c.760C>T
single nucleotide variant
 p.Gln254Ter Pathogenic ★★☆☆ Xeroderma pigmentosum group B

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

Variants in the ERCC3 gene are associated with conditions primarily characterised by defective DNA repair. These include trichothiodystrophy, which affects multiple body systems and causes brittle hair, and xeroderma pigmentosum, characterised by extreme sensitivity to ultraviolet light and increased skin cancer risk. Some individuals may present with features of both conditions, known as xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex.

No disease links recorded for this gene in our reference set.

Inheritance pattern

Conditions caused by pathogenic ERCC3 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 ERCC3 carrier status across ancestry groups?

UK clinical status

ERCC3 is included in several UK NHS national genomic testing panels. It is part of the 'Adult solid tumours cancer susceptibility', 'Childhood solid tumours cancer susceptibility', and 'Childhood solid tumours' panels. The gene is also relevant for 'Bilateral congenital or childhood onset cataracts (R31)', 'DDG2P', 'Foetal anomalies (R21)', 'Intellectual disability', and 'Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome (R227)' panels, indicating its recognised clinical significance within the NHS.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Bilateral congenital or childhood onset cataracts · R31 NHS GMS → Fetal anomalies · R21 NHS GMS → Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome · R227 NHS GMS → Adult solid tumours cancer susceptibility NHS GMS → Childhood solid tumours NHS GMS → DDG2P NHS GMS → Intellectual disability 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 main role of the ERCC3 gene?

The ERCC3 gene provides instructions for the XPB protein, which is a vital part of the TFIIH complex. This complex is crucial for both initiating gene transcription and carrying out nucleotide excision repair (NER) of damaged DNA.

Which conditions are associated with ERCC3 gene variants?

Variants in the ERCC3 gene are linked to conditions such as trichothiodystrophy, characterised by brittle hair and other symptoms, and xeroderma pigmentosum, which involves extreme sensitivity to UV light and an increased risk of skin cancer. Some individuals may present with features of both conditions, known as xeroderma pigmentosum/Cockayne syndrome complex.

How does ERCC3 contribute to DNA repair?

The ERCC3 gene's protein, XPB, is part of the TFIIH complex that participates in nucleotide excision repair (NER). This complex helps unwind the damaged section of DNA, allowing XPB to hold the strands open while other proteins remove and replace the faulty segment, thus maintaining genomic stability.

References

  1. Oksenych V, Coin F. The long unwinding road: XPB and XPD helicases in damaged DNA opening. Cell cycle (Georgetown, Tex.). 2010. PMID: 20016270
  2. Lambert WC, Gagna CE, Lambert MW. Xeroderma pigmentosum: its overlap with trichothiodystrophy, Cockayne syndrome and other progeroid syndromes. Advances in experimental medicine and biology. 2008. PMID: 19181118
  3. Coin F, Oksenych V, Egly JM. Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair. Molecular cell. 2007. PMID: 17466626
  4. Oh KS, Imoto K, Boyle J. Influence of XPB helicase on recruitment and redistribution of nucleotide excision repair proteins at sites of UV-induced DNA damage. DNA repair. 2007. PMID: 17509950
  5. Oh KS, Khan SG, Jaspers NG. Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome. Human mutation. 2006. PMID: 16947863
  6. Riou L, Zeng L, Chevallier-Lagente O. The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes. Human molecular genetics. 1999. PMID: 10332046
  7. Weeda G, Eveno E, Donker I. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. American journal of human genetics. 1997. PMID: 9012405
  8. Weeda G, van Ham RC, Vermeulen W. A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome. Cell. 1990. PMID: 2167179
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 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .