|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “xeroderma pigmentosum, complementation group A.”
XPA is the gene's official symbol. The XPA gene is also known by other names, listed below.
The XPA gene provides instructions for making a protein that is involved in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals.
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). As part of this repair mechanism, the XPA protein helps verify DNA damage and stabilize the DNA as it is repaired. The XPA protein attaches (binds) to areas of damaged DNA, where it interacts with many other proteins as part of a large complex. Proteins in this complex unwind the section of DNA where the damage has occurred, snip out (excise) the abnormal section, and replace the damaged area with the correct DNA.
At least 25 mutations in the XPA gene have been found to cause xeroderma pigmentosum. Mutations in this gene are responsible for a very severe form of the disorder that is more common in the Japanese population than in other populations. Most Japanese people with xeroderma pigmentosum have the same XPA gene mutation, which is written as IVS3AS, G>C. This mutation prevents cells from producing any functional XPA protein. Other XPA gene mutations, which have been reported in Japan and elsewhere, result in the production of a defective version of the XPA protein or greatly reduce the amount of this protein that is made in cells.
A partial or total loss of the XPA protein prevents cells from repairing DNA damage normally. As a result, abnormalities accumulate in DNA, causing cells to malfunction and eventually to become cancerous or die. These problems with DNA repair cause people with xeroderma pigmentosum to be extremely sensitive to UV rays from sunlight. When UV rays damage genes that control cell growth and division, cells can grow too fast and in an uncontrolled way. As a result, people with xeroderma pigmentosum have a greatly increased risk of developing cancer. These cancers occur most frequently in areas of the body that are exposed to the sun, such as the skin and eyes.
When xeroderma pigmentosum is caused by XPA gene mutations, it is often associated with progressive neurological abnormalities. These nervous system problems include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. The neurological abnormalities are thought to result from a buildup of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.
Cytogenetic Location: 9q22.3
Molecular Location on chromosome 9: base pairs 97,634,450 to 97,697,408
The XPA gene is located on the long (q) arm of chromosome 9 at position 22.3.
More precisely, the XPA gene is located from base pair 97,634,450 to base pair 97,697,408 on chromosome 9.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about XPA helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
cancer ; cell ; difficulty swallowing ; dimer ; DNA ; DNA damage ; DNA repair ; free radicals ; gene ; genome ; mutation ; NER ; nervous system ; neurological ; nucleotide ; nucleotide excision repair ; population ; protein ; radiation ; toxic ; transcription ; UV rays
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.