Reviewed February 2010
What is the official name of the OFD1 gene?
The official name of this gene is “oral-facial-digital syndrome 1.”
OFD1 is the gene's official symbol. The OFD1 gene is also known by other names, listed below.
What is the normal function of the OFD1 gene?
The OFD1 gene provides instructions for making a protein whose function is not fully understood. It appears to play a critical role in the early development of many parts of the body, including the brain, face, limbs, and kidneys.
The OFD1 protein is located at the base of cilia, which are finger-like projections that stick out from the surface of cells. Cilia are involved in cell movement and in many different chemical signaling pathways. They play important roles in the development and function of many parts of the body. Researchers suspect that the OFD1 protein is essential for the normal formation of cilia.
Studies suggest that the OFD1 protein may have additional functions. In the earliest stages of development, it appears to be involved in determining the left-right axis (the imaginary line that separates the left and right sides of the body). The OFD1 protein is also found in the nucleus, although its function in this cell structure is unknown.
How are changes in the OFD1 gene related to health conditions?
- oral-facial-digital syndrome - caused by mutations in the OFD1 gene
About 100 mutations in the OFD1 gene have been found in people with oral-facial-digital syndrome type I, which is the most common form of the disorder. These mutations include changes in single DNA building blocks (base pairs) and larger deletions of genetic material from the OFD1 gene. Most of these genetic changes lead to the production of an abnormally short, nonfunctional version of the OFD1 protein. It is unclear how a shortage of functional OFD1 protein leads to the specific features of oral-facial-digital syndrome type I. However, studies suggest that a lack of this protein prevents the normal formation of cilia, which affects the development of many tissues and organs.
- other disorders - caused by mutations in the OFD1 gene
Mutations in the OFD1 gene can also cause several other disorders with features that overlap with those of oral-facial-digital syndrome. At least two mutations have been identified in people with Joubert syndrome. This disorder is characterized by particular brain abnormalities, weak muscle tone (hypotonia), delayed development, unusual eye movements, and breathing problems. Another OFD1 gene mutation has been found in a family with a form of X-linked intellectual disability. Affected individuals have had severe intellectual disability, an unusually large head size (macrocephaly), and breathing problems.
The OFD1 mutations responsible for Joubert syndrome and X-linked intellectual disability lead to the production of an abnormally short version of the OFD1 protein. However, studies suggest that these mutations result in a somewhat longer protein than the mutations that cause oral-facial-digital syndrome. This protein may retain some of its usual function in cilia. The abnormal protein probably disrupts the development or function of cilia in some way, although it is unclear how these changes result in the signs and symptoms of Joubert syndrome or X-linked intellectual disability.
Where is the OFD1 gene located?
Cytogenetic Location: Xp22
Molecular Location on the X chromosome: base pairs 13,715,429 to 13,769,360
The OFD1 gene is located on the short (p) arm of the X chromosome at position 22.
More precisely, the OFD1 gene is located from base pair 13,715,429 to base pair 13,769,360 on the X chromosome.
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 OFD1?
You and your healthcare professional may find the following resources about OFD1 helpful.
Educational resources - Information pages
- Kennedy Krieger Institute: X-linked Mental Retardation (http://gcbcenter.kennedykrieger.org/xmr.jsp)
- Molecular Biology of the Cell (fourth edition, 2002): Cilia and Flagella Are Motile Structures Built from Microtubules and Dyneins (http://www.ncbi.nlm.nih.gov/books/NBK26888/)
- Molecular Cell Biology (first edition, 2000): Cilia and Flagella: Structure and Movement (http://www.ncbi.nlm.nih.gov/books/NBK21698/)
Gene Reviews - Clinical summary
- Gene Review: Joubert Syndrome and Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1325/)
- Gene Review: Oral-Facial-Digital Syndrome Type I (http://www.ncbi.nlm.nih.gov/books/NBK1188/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for OFD1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=8481%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=(OFD1%5BTIAB%5D)%20OR%20((SGBS2%5BTIAB%5D)%20OR%20(CXorf5%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- JOUBERT SYNDROME 10 (http://omim.org/entry/300804)
- OFD1 GENE (http://omim.org/entry/300170)
Research Resources - Tools for researchers
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=8481)
- HGNC Gene Symbol Report (http://www.genenames.org/data/hgnc_data.php?hgnc_id=2567)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8481)
What other names do people use for the OFD1 gene or gene products?
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 OFD1?
mental retardation ;
muscle tone ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Budny B, Chen W, Omran H, Fliegauf M, Tzschach A, Wisniewska M, Jensen LR, Raynaud M, Shoichet SA, Badura M, Lenzner S, Latos-Bielenska A, Ropers HH. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet. 2006 Sep;120(2):171-8. Epub 2006 Jun 17. (http://www.ncbi.nlm.nih.gov/pubmed/16783569?dopt=Abstract)
- Coene KL, Roepman R, Doherty D, Afroze B, Kroes HY, Letteboer SJ, Ngu LH, Budny B, van Wijk E, Gorden NT, Azhimi M, Thauvin-Robinet C, Veltman JA, Boink M, Kleefstra T, Cremers FP, van Bokhoven H, de Brouwer AP. OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin. Am J Hum Genet. 2009 Oct;85(4):465-81. doi: 10.1016/j.ajhg.2009.09.002. (http://www.ncbi.nlm.nih.gov/pubmed/19800048?dopt=Abstract)
- Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B. Identification of the gene for oral-facial-digital type I syndrome. Am J Hum Genet. 2001 Mar;68(3):569-76. Epub 2001 Feb 13. (http://www.ncbi.nlm.nih.gov/pubmed/11179005?dopt=Abstract)
- Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dollé P, Franco B. Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet. 2006 Jan;38(1):112-7. Epub 2005 Nov 27. (http://www.ncbi.nlm.nih.gov/pubmed/16311594?dopt=Abstract)
- Giorgio G, Alfieri M, Prattichizzo C, Zullo A, Cairo S, Franco B. Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with subunits of a chromatin remodeling complex. Mol Biol Cell. 2007 Nov;18(11):4397-404. Epub 2007 Aug 29. (http://www.ncbi.nlm.nih.gov/pubmed/17761535?dopt=Abstract)
- Macca M, Franco B. The molecular basis of oral-facial-digital syndrome, type 1. Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):318-25. doi: 10.1002/ajmg.c.30224. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19876934?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8481)
- Prattichizzo C, Macca M, Novelli V, Giorgio G, Barra A, Franco B; Oral-Facial-Digital Type I (OFDI) Collaborative Group. Mutational spectrum of the oral-facial-digital type I syndrome: a study on a large collection of patients. Hum Mutat. 2008 Oct;29(10):1237-46. doi: 10.1002/humu.20792. (http://www.ncbi.nlm.nih.gov/pubmed/18546297?dopt=Abstract)
- Romio L, Fry AM, Winyard PJ, Malcolm S, Woolf AS, Feather SA. OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelial transition in human nephrogenesis. J Am Soc Nephrol. 2004 Oct;15(10):2556-68. (http://www.ncbi.nlm.nih.gov/pubmed/15466260?dopt=Abstract)
- Thauvin-Robinet C, Cossée M, Cormier-Daire V, Van Maldergem L, Toutain A, Alembik Y, Bieth E, Layet V, Parent P, David A, Goldenberg A, Mortier G, Héron D, Sagot P, Bouvier AM, Huet F, Cusin V, Donzel A, Devys D, Teyssier JR, Faivre L. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study. J Med Genet. 2006 Jan;43(1):54-61. (http://www.ncbi.nlm.nih.gov/pubmed/16397067?dopt=Abstract)
- Thauvin-Robinet C, Franco B, Saugier-Veber P, Aral B, Gigot N, Donzel A, Van Maldergem L, Bieth E, Layet V, Mathieu M, Teebi A, Lespinasse J, Callier P, Mugneret F, Masurel-Paulet A, Gautier E, Huet F, Teyssier JR, Tosi M, Frébourg T, Faivre L. Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing. Hum Mutat. 2009 Feb;30(2):E320-9. doi: 10.1002/humu.20888. (http://www.ncbi.nlm.nih.gov/pubmed/19023858?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.