Reviewed February 2014
What is the official name of the ORC1 gene?
The official name of this gene is “origin recognition complex subunit 1.”
ORC1 is the gene's official symbol. The ORC1 gene is also known by other names, listed below.
What is the normal function of the ORC1 gene?
The ORC1 gene provides instructions for making a protein that is important in the copying of a cell's DNA before the cell divides (a process known as DNA replication). The protein produced from this gene is one of a group of proteins known as the origin recognition complex (ORC). (The complex is made up of the proteins ORC1 to ORC6, which are produced from different genes.) ORC attaches (binds) to certain regions of DNA known as origins of replication (or origins), where the process of DNA copying begins. This complex attracts additional proteins to bind to it, forming a larger group of proteins called the pre-replication complex. When the pre-replication complex is attached to the origin, replication is able to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide.
ORC also attaches to a form of DNA called heterochromatin. Heterochromatin is densely packed DNA that contains few functional genes, but it is important for controlling gene activity and maintaining the structure of chromosomes. It is unclear what effect ORC binding has on heterochromatin.
In addition to its roles as part of ORC, the ORC1 protein is involved in the copying of cell structures called centrosomes and centrioles, which are important for the process of cell division. ORC1 blocks centrosomes and centrioles from being copied more than once, which is key to normal cell division. In addition, some research suggests that ORC1 is involved in the function of cilia, which are microscopic, finger-like projections that stick out from the surface of cells. Cilia participate in signaling pathways that transmit information within and between cells and are important for the development and function of many types of cells and tissues, including bone.
Does the ORC1 gene share characteristics with other genes?
The ORC1 gene belongs to a family of genes called ATP (ATPases).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the ORC1 gene related to health conditions?
- Meier-Gorlin syndrome - caused by mutations in the ORC1 gene
Mutations in the ORC1 gene cause Meier-Gorlin syndrome, a condition characterized by short stature, underdeveloped kneecaps, and small ears. These mutations alter the ORC1 protein, typically by changing single protein building blocks (amino acids) or by leading to production of an abnormally short version of the ORC1 protein. As a result, assembly of the pre-replication complex is impaired, which disrupts replication licensing; however, it is not clear how a reduction in replication licensing leads to Meier-Gorlin syndrome. Researchers speculate that such a reduction delays the cell division process, which slows growth of the bones and other tissues during development and may contribute to the features of the disorder. Some studies suggest that alterations of ORC1 result in too many copies of centrosomes and centrioles, which may also delay cell division. Other studies suggest that changes in ORC1 impair the function of cilia, which may delay development of certain tissues and underlie the abnormal development of kneecaps and ears characteristic of Meier-Gorlin syndrome.
Where is the ORC1 gene located?
Cytogenetic Location: 1p32
Molecular Location on chromosome 1: base pairs 52,372,829 to 52,404,471
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/4998))
The ORC1 gene is located on the short (p) arm of chromosome 1 at position 32.
More precisely, the ORC1 gene is located from base pair 52,372,829 to base pair 52,404,471 on chromosome 1.
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 ORC1?
You and your healthcare professional may find the following resources about ORC1 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2002): DNA Synthesis Begins at Replication Origins (http://www.ncbi.nlm.nih.gov/books/NBK26826/)
- The Cell: A Molecular Approach (second edition, 2000): Origins and the Initiation of Replication (http://www.ncbi.nlm.nih.gov/books/NBK9940/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for ORC1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4998%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=%28ORC1%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/601902)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_ORC1.html)
- HGNC Gene Family: AAA ATPases (ATPases associated with diverse cellular activities) (http://www.genenames.org/cgi-bin/genefamilies/set/413)
- HGNC Gene Family: Origin recognition complex (http://www.genenames.org/cgi-bin/genefamilies/set/960)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=8487)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4998)
What other names do people use for the ORC1 gene or gene products?
- origin recognition complex, subunit 1
- origin recognition complex, subunit 1 homolog
- replication control protein 1
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 ORC1?
cell division ;
DNA replication ;
short stature ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bicknell LS, Bongers EM, Leitch A, Brown S, Schoots J, Harley ME, Aftimos S, Al-Aama JY, Bober M, Brown PA, van Bokhoven H, Dean J, Edrees AY, Feingold M, Fryer A, Hoefsloot LH, Kau N, Knoers NV, Mackenzie J, Opitz JM, Sarda P, Ross A, Temple IK, Toutain A, Wise CA, Wright M, Jackson AP. Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nat Genet. 2011 Feb 27;43(4):356-9. doi: 10.1038/ng.775. (http://www.ncbi.nlm.nih.gov/pubmed/21358632?dopt=Abstract)
- Bicknell LS, Walker S, Klingseisen A, Stiff T, Leitch A, Kerzendorfer C, Martin CA, Yeyati P, Al Sanna N, Bober M, Johnson D, Wise C, Jackson AP, O'Driscoll M, Jeggo PA. Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nat Genet. 2011 Feb 27;43(4):350-5. doi: 10.1038/ng.776. (http://www.ncbi.nlm.nih.gov/pubmed/21358633?dopt=Abstract)
- de Munnik SA, Bicknell LS, Aftimos S, Al-Aama JY, van Bever Y, Bober MB, Clayton-Smith J, Edrees AY, Feingold M, Fryer A, van Hagen JM, Hennekam RC, Jansweijer MC, Johnson D, Kant SG, Opitz JM, Ramadevi AR, Reardon W, Ross A, Sarda P, Schrander-Stumpel CT, Schoots J, Temple IK, Terhal PA, Toutain A, Wise CA, Wright M, Skidmore DL, Samuels ME, Hoefsloot LH, Knoers NV, Brunner HG, Jackson AP, Bongers EM. Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis. Eur J Hum Genet. 2012 Jun;20(6):598-606. doi: 10.1038/ejhg.2011.269. Epub 2012 Feb 15. (http://www.ncbi.nlm.nih.gov/pubmed/22333897?dopt=Abstract)
- Hemerly AS, Prasanth SG, Siddiqui K, Stillman B. Orc1 controls centriole and centrosome copy number in human cells. Science. 2009 Feb 6;323(5915):789-93. doi: 10.1126/science.1166745. (http://www.ncbi.nlm.nih.gov/pubmed/19197067?dopt=Abstract)
- Hossain M, Stillman B. Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication. Genes Dev. 2012 Aug 15;26(16):1797-810. doi: 10.1101/gad.197178.112. Epub 2012 Aug 1. (http://www.ncbi.nlm.nih.gov/pubmed/22855792?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4998)
- Niida H, Kitagawa M. Regulation of DNA replication licensing. Curr Drug Targets. 2012 Dec;13(13):1588-92. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22998185?dopt=Abstract)
- OMIM: ORIGIN RECOGNITION COMPLEX, SUBUNIT 1, S. CEREVISIAE, HOMOLOG OF (http://omim.org/entry/601902)
- Prasanth SG, Shen Z, Prasanth KV, Stillman B. Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15093-8. doi: 10.1073/pnas.1009945107. Epub 2010 Aug 5. (http://www.ncbi.nlm.nih.gov/pubmed/20689044?dopt=Abstract)
- Stiff T, Alagoz M, Alcantara D, Outwin E, Brunner HG, Bongers EM, O'Driscoll M, Jeggo PA. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome. PLoS Genet. 2013;9(3):e1003360. doi: 10.1371/journal.pgen.1003360. Epub 2013 Mar 14. (http://www.ncbi.nlm.nih.gov/pubmed/23516378?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.