GENE REFERENCE / HGNC:3434

ERCC2

ERCC excision repair 2, TFIIH core complex helicase subunit

protein-coding gene19q13.32Gene information

What does this gene do?

The ERCC2 gene provides instructions for making a protein called XPD. This protein is an essential part (subunit) of a group of proteins known as the general transcription factor 2 H (TFIIH) complex. The TFIIH complex has two major functions: it is involved in a process called gene transcription, and it helps repair damaged DNA.

Gene transcription is the first step in protein production. By controlling gene transcription, the TFIIH complex helps regulate the activity of many different genes. The XPD protein appears to stabilize the TFIIH complex. Studies suggest that the XPD protein works together with XPB, another protein in the TFIIH complex that is produced from the ERCC3 gene, to start (initiate) gene transcription.

The TFIIH complex also plays an important role in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from sunlight and by toxic chemicals, such as those found in cigarette smoke. DNA damage occurs frequently, but normal cells are usually able to fix it before it can cause problems.

One of the major mechanisms that cells use to fix DNA is known as nucleotide excision repair (NER). The TFIIH complex is part of this repair mechanism. The XPD protein acts as a helicase, which is an enzyme that attaches (binds) to particular regions of DNA and temporarily unwinds the two spiral strands. Once the damaged region has been exposed, other proteins snip out (excise) the abnormal section and replace the damaged area with the correct DNA.

Source: MedlinePlus, National Library of Medicine. Source publication: 2023-04-06. Source review: 2023-04.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
xeroderma pigmentosum group DMONDO:0010212 · Evaluated 2019-04-19	Autosomal recessive	DefinitiveHereditary Cancer Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 2,466
Submissions for variants in or overlapping this gene: 3,877
Submissions explicitly reporting this gene: 3,773
Alleles reported pathogenic / likely pathogenic: 280
VariationIDs with uncertain significance: 1,002
VariationIDs with conflicting classifications: 74

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about ERCC2?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 280 alleles in ERCC2 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in ERCC2.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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