What symptoms might indicate a problem with the ERCC2 gene’s DNA repair function?

Early signs include sunburns that heal slowly, freckling or pigmentation changes on sun‑exposed skin, and a higher frequency of skin cancers such as basal cell carcinoma or squamous cell carcinoma. Neurological symptoms—such as speech delays, hearing loss, or balance issues—may appear if the mutation affects the nervous system.

What disorders are associated with mutations in the ERCC2 gene?

Mutations in ERCC2 can cause xeroderma pigmentosum group D (XP‑D), a condition marked by extreme sensitivity to sunlight, early skin cancers, and, in some cases, neurological or developmental abnormalities. Some variants also predispose to Cockayne syndrome, characterized by growth failure and neurodegeneration.

How are ERCC2 mutations detected, and what should I do before the test?

genetic counselor will order a targeted gene panel or whole‑exome sequencing. No special fasting is required, but avoid taking medications that might interfere with blood tests (e.g., high‑dose steroids) unless advised otherwise. Bring a detailed family history, as ERCC2 mutations are inherited in an autosomal recessive pattern.

What precautions can I take to protect my skin and overall health if I have an ERCC2 mutation?

Use broad‑spectrum sunscreen (SPF 50+) every day, wear protective clothing, and avoid peak UV hours (10 am–4 pm). Schedule regular dermatologic exams every 3–6 months for early cancer detection. If you have neurological symptoms, follow up with a neurologist for monitoring and supportive care.===

ERCC2 gene

The ERCC2 gene provides instructions for making the XPD protein, which is essential for DNA repair and gene transcription within the TFIIH complex.

Normal Function

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.

Health Conditions Related to Genetic Changes

Trichothiodystrophy

Many variants (also called mutations) in the ERCC2 gene have been found to cause trichothiodystrophy. This condition affects many parts of the body. The hallmark of trichothiodystrophy is hair that is sparse and easily broken. Affected children may develop severe hip degeneration.

Variants in this gene are the most common cause of the photosensitive form of the condition, which is characterized by an extreme sensitivity to UV rays from sunlight.
Studies suggest that the ERCC2 gene variants responsible for trichothiodystrophy reduce the amount of functional TFIIH complex in cells.
Unlike xeroderma pigmentosum, trichothiodystrophy is not associated with an increased risk of skin cancer.

Xeroderma pigmentosum

More than two dozen variants in the ERCC2 gene have been identified in people with xeroderma pigmentosum. This condition is characterized by an extreme sensitivity to UV rays from sunlight, mostly affecting the eyes and areas of skin exposed to the sun.

Variants in the ERCC2 gene are the second most common cause of xeroderma pigmentosum in the United States.
These variants prevent the TFIIH complex from repairing damaged DNA effectively, leading to a greatly increased risk of developing cancer in sun-exposed areas.
When caused by ERCC2 gene variants, it is often associated with progressive neurological abnormalities, including hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures.

Other disorders

Rarely, variants in the ERCC2 gene can cause features of both xeroderma pigmentosum and trichothiodystrophy in the same individual, known as xeroderma pigmentosum/trichothiodystrophy (XP/TTD) complex. ERCC2 gene variants have also been identified in a few individuals with signs and symptoms of both xeroderma pigmentosum and Cockayne syndrome, known as xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex.

Other Names for This Gene

basic transcription factor 2 80 kDa subunit
BTF2 p80
COFS2
CXPD
DNA excision repair protein ERCC-2
DNA repair protein complementing XP-D cells
EM9
ERCC2_HUMAN
excision repair cross-complementation group 2
excision repair cross-complementing rodent repair deficiency, complementation group 2
MAG
MGC102762
MGC126218
MGC126219
TFIIH
TFIIH 80 kDa subunit
TFIIH basal transcription factor complex 80 kDa subunit
TFIIH basal transcription factor complex helicase subunit
TFIIH p80
TTD
xeroderma pigmentosum complementary group D
xeroderma pigmentosum group D-complementing protein