Normal Function
The ROR2 gene provides instructions for making a protein whose function is not well understood. The ROR2 protein is part of a family of proteins known as receptor tyrosine kinases (RTKs), which play a role in chemical signaling within cells. RTKs are involved in many cell functions, including cell growth and division (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell survival, and cell movement (motility).
Researchers believe that the ROR2 protein plays an essential role in development starting before birth. It is involved in chemical signaling pathways called Wnt signaling, which affect many aspects of development. These pathways control the activity of genes needed at specific times, and they regulate the interactions between cells as organs and tissues are forming. In particular, the ROR2 protein appears to be critical for the normal formation of the skeleton, heart, and genitals.
Health Conditions Related to Genetic Changes
Robinow syndrome
At least 20 mutations in the ROR2 gene have been found to cause the autosomal recessive form of Robinow syndrome, a condition that affects the development of many parts of the body, particularly the bones. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. Some of these mutations change single protein building blocks (amino acids) in the ROR2 protein, while others lead to the production of an abnormally short, nonfunctional version of the protein. Because these genetic changes prevent any functional ROR2 protein from being made, they are described as "loss-of-function" mutations. Loss of ROR2 protein function impairs chemical signaling pathways that are important for normal development, particularly the formation of bones in the face, spine, and limbs. These changes lead to the skeletal abnormalities characteristic of Robinow syndrome. A lack of this protein during early development also underlies the other features of Robinow syndrome, including genital abnormalities and heart defects.
More About This Health ConditionOther disorders
More than 10 mutations in the ROR2 gene have been identified in people with a disorder called brachydactyly type B1. This condition is characterized by abnormally short fingers and toes, particularly the fourth and fifth digits, and malformed or absent fingernails and toenails. (The term "brachydactyly" is from the Greek words for "short digits.") Brachydactyly type B1 has an autosomal dominant pattern of inheritance, which means one altered copy of the gene in each cell is sufficient to cause the disorder. Unlike the mutations that cause Robinow syndrome (described above), the ROR2 gene mutations that cause brachydactyly type B1 are described as "gain-of-function" because they appear to cause the ROR2 protein to be continuously active. It is unclear how the overactive protein disrupts the development of bones in the hands and feet.
Other Names for This Gene
- BDB1
- brachydactyly type B1 gene
- neurotrophic tyrosine kinase receptor-related 2 gene
- NTRKR2
- receptor tyrosine kinase-like orphan receptor 2
- ROR2_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Afzal AR, Jeffery S. One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B. Hum Mutat. 2003 Jul;22(1):1-11. doi: 10.1002/humu.10233. Citation on PubMed
- Afzal AR, Rajab A, Fenske CD, Oldridge M, Elanko N, Ternes-Pereira E, Tuysuz B, Murday VA, Patton MA, Wilkie AO, Jeffery S. Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2. Nat Genet. 2000 Aug;25(4):419-22. doi: 10.1038/78107. Citation on PubMed
- Aglan M, Amr K, Ismail S, Ashour A, Otaify GA, Mehrez MA, Aboul-Ezz EH, El-Ruby M, Mazen I, Abdel-Hamid MS, Temtamy SA. Clinical and molecular characterization of seven Egyptian families with autosomal recessive robinow syndrome: Identification of four novel ROR2 gene mutations. Am J Med Genet A. 2015 Dec;167A(12):3054-61. doi: 10.1002/ajmg.a.37287. Epub 2015 Aug 18. Citation on PubMed
- Bacino CA. ROR2-Related Robinow Syndrome. 2005 Jul 28 [updated 2019 Sep 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1240/ Citation on PubMed
- Oldridge M, Fortuna AM, Maringa M, Propping P, Mansour S, Pollitt C, DeChiara TM, Kimble RB, Valenzuela DM, Yancopoulos GD, Wilkie AO. Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type B. Nat Genet. 2000 Mar;24(3):275-8. doi: 10.1038/73495. Citation on PubMed
- Schwabe GC, Tinschert S, Buschow C, Meinecke P, Wolff G, Gillessen-Kaesbach G, Oldridge M, Wilkie AO, Komec R, Mundlos S. Distinct mutations in the receptor tyrosine kinase gene ROR2 cause brachydactyly type B. Am J Hum Genet. 2000 Oct;67(4):822-31. doi: 10.1086/303084. Epub 2000 Sep 12. Citation on PubMed or Free article on PubMed Central
- Stricker S, Rauschenberger V, Schambony A. ROR-Family Receptor Tyrosine Kinases. Curr Top Dev Biol. 2017;123:105-142. doi: 10.1016/bs.ctdb.2016.09.003. Epub 2016 Oct 31. Citation on PubMed
- van Bokhoven H, Celli J, Kayserili H, van Beusekom E, Balci S, Brussel W, Skovby F, Kerr B, Percin EF, Akarsu N, Brunner HG. Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome. Nat Genet. 2000 Aug;25(4):423-6. doi: 10.1038/78113. Citation on PubMed
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