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Genetics Home Reference: your guide to understanding genetic conditions
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RECQL4

Reviewed August 2013

What is the official name of the RECQL4 gene?

The official name of this gene is “RecQ protein-like 4.”

RECQL4 is the gene's official symbol. The RECQL4 gene is also known by other names, listed below.

What is the normal function of the RECQL4 gene?

The RECQL4 gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. Because RecQ helicases maintain the structure and integrity of DNA, they are known as the "caretakers of the genome."

The RECQL4 protein is active in several types of cells before and after birth. Researchers believe that this protein is particularly important in cells of the developing bones and skin. It has also been found in enterocytes, which are cells that line the intestine and absorb nutrients.

How are changes in the RECQL4 gene related to health conditions?

Baller-Gerold syndrome - caused by mutations in the RECQL4 gene

Several mutations in the RECQL4 gene have been identified in people with Baller-Gerold syndrome. Most of these mutations prevent the production of any RECQL4 protein or change the way the protein is pieced together, which disrupts its usual function. A shortage of this protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how these changes result in the varied signs and symptoms of Baller-Gerold syndrome, including the abnormal fusion of certain skull bones (craniosynostosis), small stature, missing thumbs or bones in the forearm (radial ray malformations), and a skin rash.

RAPADILINO syndrome - caused by mutations in the RECQL4 gene

At least 10 mutations in the RECQL4 gene have been identified in people with RAPADILINO syndrome. This condition has many features, including radial ray malformations, malformed or missing kneecaps, diarrhea, and short stature. The condition was first identified in Finland, and the most common mutation in RAPADILINO syndrome is found in all affected individuals of Finnish descent as well as some people from other populations. This mutation, which is written as IVS7+2delT, is known as a splice-site mutation, and it causes the RECQL4 protein to be pieced together incorrectly. This genetic change results in the production of a protein that is missing a region called exon 7. The altered protein does not have helicase activity, which may prevent normal DNA replication and repair. These changes may result in the accumulation of DNA errors and cell death, although it is unclear exactly how RECQL4 gene mutations lead to the specific features of RAPADILINO syndrome.

Rothmund-Thomson syndrome - caused by mutations in the RECQL4 gene

More than 40 mutations in the RECQL4 gene have been found in people with Rothmund-Thomson syndrome. These mutations likely prevent the production of any RECQL4 protein or lead to the production of an abnormally short, nonfunctional version of the protein. A shortage of this protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. Further study is needed to determine how these changes result in the characteristic features of Rothmund-Thomson syndrome, which include a skin rash, sparse hair, small stature, skeletal abnormalities, and an increased risk of certain cancers.

Because Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO syndrome have overlapping features and can be caused by mutations in the same gene, researchers are investigating whether they are separate disorders or part of a single syndrome with overlapping signs and symptoms.

Where is the RECQL4 gene located?

Cytogenetic Location: 8q24.3

Molecular Location on chromosome 8: base pairs 144,511,283 to 144,517,826

The RECQL4 gene is located on the long (q) arm of chromosome 8 at position 24.3.

The RECQL4 gene is located on the long (q) arm of chromosome 8 at position 24.3.

More precisely, the RECQL4 gene is located from base pair 144,511,283 to base pair 144,517,826 on chromosome 8.

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 RECQL4?

You and your healthcare professional may find the following resources about RECQL4 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the RECQL4 gene or gene products?

  • ATP-Dependent DNA Helicase Q4
  • RECQ4
  • RECQ4_HUMAN
  • RecQ protein 4
  • RecQ Protein Like 4
  • RTS

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 RECQL4?

ATP ; cell ; cell division ; craniosynostosis ; DNA ; DNA replication ; double helix ; exon ; gene ; genome ; helicase ; intestine ; molecule ; mutation ; protein ; short stature ; splice-site mutation ; stature ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Croteau DL, Rossi ML, Ross J, Dawut L, Dunn C, Kulikowicz T, Bohr VA. RAPADILINO RECQL4 mutant protein lacks helicase and ATPase activity. Biochim Biophys Acta. 2012 Nov;1822(11):1727-34. doi: 10.1016/j.bbadis.2012.07.014. Epub 2012 Jul 31. (http://www.ncbi.nlm.nih.gov/pubmed/22885111?dopt=Abstract)
  • Croteau DL, Singh DK, Hoh Ferrarelli L, Lu H, Bohr VA. RECQL4 in genomic instability and aging. Trends Genet. 2012 Dec;28(12):624-31. doi: 10.1016/j.tig.2012.08.003. Epub 2012 Aug 30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22940096?dopt=Abstract)
  • Dietschy T, Shevelev I, Stagljar I. The molecular role of the Rothmund-Thomson-, RAPADILINO- and Baller-Gerold-gene product, RECQL4: recent progress. Cell Mol Life Sci. 2007 Apr;64(7-8):796-802. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17364146?dopt=Abstract)
  • Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet. 1999 May;22(1):82-4. (http://www.ncbi.nlm.nih.gov/pubmed/10319867?dopt=Abstract)
  • Larizza L, Magnani I, Roversi G. Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping. Cancer Lett. 2006 Jan 28;232(1):107-20. Epub 2005 Nov 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16271439?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9401)
  • Petkovic M, Dietschy T, Freire R, Jiao R, Stagljar I. The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J Cell Sci. 2005 Sep 15;118(Pt 18):4261-9. Epub 2005 Sep 1. Erratum in: J Cell Sci. 2005 Oct 1;118(Pt 19):4587. (http://www.ncbi.nlm.nih.gov/pubmed/16141230?dopt=Abstract)
  • Siitonen HA, Kopra O, Kääriäinen H, Haravuori H, Winter RM, Säämänen AM, Peltonen L, Kestilä M. Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum Mol Genet. 2003 Nov 1;12(21):2837-44. Epub 2003 Sep 2. (http://www.ncbi.nlm.nih.gov/pubmed/12952869?dopt=Abstract)
  • Suzuki T, Kohno T, Ishimi Y. DNA helicase activity in purified human RECQL4 protein. J Biochem. 2009 Sep;146(3):327-35. doi: 10.1093/jb/mvp074. Epub 2009 May 18. (http://www.ncbi.nlm.nih.gov/pubmed/19451148?dopt=Abstract)
  • Van Maldergem L, Siitonen HA, Jalkh N, Chouery E, De Roy M, Delague V, Muenke M, Jabs EW, Cai J, Wang LL, Plon SE, Fourneau C, Kestilä M, Gillerot Y, Mégarbané A, Verloes A. Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene. J Med Genet. 2006 Feb;43(2):148-52. Epub 2005 Jun 17. (http://www.ncbi.nlm.nih.gov/pubmed/15964893?dopt=Abstract)
  • Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, Ruiz-Maldanado R, Contreras-Ruiz J, Cunniff C, Erickson RP, Lev D, Rogers M, Zackai EH, Plon SE. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. 2003 May 7;95(9):669-74. (http://www.ncbi.nlm.nih.gov/pubmed/12734318?dopt=Abstract)
  • Werner SR, Prahalad AK, Yang J, Hock JM. RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome. Biochem Biophys Res Commun. 2006 Jun 23;345(1):403-9. Epub 2006 Apr 27. (http://www.ncbi.nlm.nih.gov/pubmed/16678792?dopt=Abstract)
  • Yin J, Kwon YT, Varshavsky A, Wang W. RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. Hum Mol Genet. 2004 Oct 15;13(20):2421-30. Epub 2004 Aug 18. (http://www.ncbi.nlm.nih.gov/pubmed/15317757?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2013
Published: March 23, 2015