Reviewed May 2010
What is the official name of the GTF2H5 gene?
The official name of this gene is “general transcription factor IIH, polypeptide 5.”
GTF2H5 is the gene's official symbol. The GTF2H5 gene is also known by other names, listed below.
What is the normal function of the GTF2H5 gene?
The GTF2H5 gene provides instructions for making a protein called p8 or TTDA. This protein is one part (subunit) of a group of related proteins known as the general transcription factor IIH (TFIIH) complex. The TFIIH complex has two major functions: it is involved in the process of gene transcription, which is the first step in protein production, and it helps repair 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 TFIIH complex opens up the section of double-stranded DNA that surrounds the damage. The TTDA protein helps with this process by stabilizing the TFIIH complex and maintaining its structure. Once the damaged region has been exposed, other proteins snip out (excise) the abnormal section and replace the damaged area with the correct DNA.
How are changes in the GTF2H5 gene related to health conditions?
- trichothiodystrophy - caused by mutations in the GTF2H5 gene
At least three mutations in the GTF2H5 gene have been found to cause trichothiodystrophy. Mutations in this gene cause the photosensitive form of the condition, which is characterized by an extreme sensitivity to UV rays from sunlight.
Each of the known GTF2H5 gene mutations results in the production of a nonfunctional version of the TTDA protein. A loss of this protein probably causes the TFIIH complex to become unstable, which greatly reduces the amount of this complex within cells. Without enough of the TFIIH complex, cells cannot effectively repair DNA damage caused by UV radiation. These problems with DNA repair cause people with the photosensitive form of trichothiodystrophy to be extremely sensitive to sunlight. It is unclear how a loss of the TTDA protein leads to the other features of the condition, such as slow growth, intellectual disability, and brittle hair.
Where is the GTF2H5 gene located?
Cytogenetic Location: 6q25.3
Molecular Location on chromosome 6: base pairs 158,168,346 to 158,199,343
The GTF2H5 gene is located on the long (q) arm of chromosome 6 at position 25.3.
More precisely, the GTF2H5 gene is located from base pair 158,168,346 to base pair 158,199,343 on chromosome 6.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about GTF2H5?
You and your healthcare professional may find the following resources about GTF2H5 helpful.
Educational resources - Information pages
- Cancer Medicine (sixth edition, 2003): Steps in Nucleotide Excision Repair (image) (http://www.ncbi.nlm.nih.gov/books/NBK13017/?rendertype=figure&id=A5537)
- Madame Curie Bioscience Database: Trichothiodystrophy: A Disorder Highlighting the Crosstalk between DNA Repair and Transcription (http://www.ncbi.nlm.nih.gov/books/NBK6285/)
- The Cell: A Molecular Approach (second edition, 2000): DNA Repair (http://www.ncbi.nlm.nih.gov/books/NBK9900/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for GTF2H5 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=404672%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(GTF2H5%5BTIAB%5D)%20OR%20((TFB5%5BTIAB%5D)%20OR%20(TTD-A%5BTIAB%5D)%20OR%20(TTDA%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/608780)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_GTF2H5.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=404672)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=21157)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/404672)
What other names do people use for the GTF2H5 gene or gene products?
- general transcription factor IIH subunit 5
- TFB5 ortholog
- TFIIH basal transcription factor complex TTDA subunit
- TFIIH basal transcription factor complex TTD-A subunit
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding GTF2H5?
DNA damage ;
DNA repair ;
free radicals ;
gene transcription ;
nucleotide excision repair ;
transcription factor ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Coin F, Proietti De Santis L, Nardo T, Zlobinskaya O, Stefanini M, Egly JM. p8/TTD-A as a repair-specific TFIIH subunit. Mol Cell. 2006 Jan 20;21(2):215-26. (http://www.ncbi.nlm.nih.gov/pubmed/16427011?dopt=Abstract)
- Faghri S, Tamura D, Kraemer KH, Digiovanna JJ. Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations. J Med Genet. 2008 Oct;45(10):609-21. doi: 10.1136/jmg.2008.058743. Epub 2008 Jun 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18603627?dopt=Abstract)
- Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W. A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A. Nat Genet. 2004 Jul;36(7):714-9. Epub 2004 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/15220921?dopt=Abstract)
- Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, Ng JM, Dinant C, Hoeijmakers JH, Vermeulen W. Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells. PLoS Biol. 2006 Jun;4(6):e156. Epub 2006 May 9. (http://www.ncbi.nlm.nih.gov/pubmed/16669699?dopt=Abstract)
- Hashimoto S, Egly JM. Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH. Hum Mol Genet. 2009 Oct 15;18(R2):R224-30. doi: 10.1093/hmg/ddp390. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19808800?dopt=Abstract)
- Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience. 2007 Apr 14;145(4):1388-96. Epub 2007 Feb 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17276014?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/404672)
- Ranish JA, Hahn S, Lu Y, Yi EC, Li XJ, Eng J, Aebersold R. Identification of TFB5, a new component of general transcription and DNA repair factor IIH. Nat Genet. 2004 Jul;36(7):707-13. Epub 2004 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/15220919?dopt=Abstract)
- Vermeulen W, Bergmann E, Auriol J, Rademakers S, Frit P, Appeldoorn E, Hoeijmakers JH, Egly JM. Sublimiting concentration of TFIIH transcription/DNA repair factor causes TTD-A trichothiodystrophy disorder. Nat Genet. 2000 Nov;26(3):307-13. (http://www.ncbi.nlm.nih.gov/pubmed/11062469?dopt=Abstract)
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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.