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Genetics Home Reference: your guide to understanding genetic conditions
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EVC2

Reviewed December 2012

What is the official name of the EVC2 gene?

The official name of this gene is “Ellis van Creveld syndrome 2.”

EVC2 is the gene's official symbol. The EVC2 gene is also known by other names, listed below.

What is the normal function of the EVC2 gene?

The EVC2 gene provides instructions for making a protein whose function is unknown. However, it appears to be important for normal growth and development, particularly the development of bones and teeth. The EVC2 protein is found in primary cilia, which are microscopic, finger-like projections that stick out from the surface of cells and are involved in signaling pathways that transmit information between cells. In particular, the EVC2 protein is thought to help regulate a signaling pathway known as Sonic Hedgehog, which plays roles in cell growth, cell specialization, and the normal shaping (patterning) of many parts of the body.

EVC2 and another gene, EVC, are located very close together on chromosome 4. Researchers believe that the two genes may have related functions and that their activity may be coordinated.

How are changes in the EVC2 gene related to health conditions?

Ellis-van Creveld syndrome - caused by mutations in the EVC2 gene

More than 30 mutations in the EVC2 gene have been found to cause Ellis-van Creveld syndrome, an inherited disorder characterized by dwarfism, abnormal nails and teeth, and heart defects. The mutations that cause this condition occur in both copies of the EVC2 gene in each cell. Most of the genetic changes lead to the production of an abnormally small, nonfunctional version of the EVC2 protein. Although it is unclear how the loss of this protein's function underlies the signs and symptoms of Ellis-van Creveld syndrome, researchers believe that it may prevent normal Sonic Hedgehog signaling in the developing embryo. Problems with this signaling pathway may ultimately lead to the abnormal bone growth and heart defects seen with this condition.

Weyers acrofacial dysostosis - caused by mutations in the EVC2 gene

At least three mutations in the EVC2 gene have been found to cause Weyers acrofacial dysostosis, a condition that affects the development of the teeth, nails, and bones. Its signs and symptoms are similar to, but typically milder than, those of Ellis-van Creveld syndrome.

The mutations that cause Weyers acrofacial dysostosis occur in one copy of the EVC2 gene in each cell. Each mutation changes a single protein building block (amino acid) near the end of the EVC2 protein. These mutations probably result in the production of an abnormally short, malfunctioning version of the protein. It is unclear how the defective protein leads to the specific features of Weyers acrofacial dysostosis. Studies suggest that it interferes with Sonic Hedgehog signaling in the developing embryo, disrupting the normal formation and growth of the teeth, nails, and bones.

Where is the EVC2 gene located?

Cytogenetic Location: 4p16.2-p16.1

Molecular Location on chromosome 4: base pairs 5,562,418 to 5,709,547

The EVC2 gene is located on the short (p) arm of chromosome 4 between positions 16.2 and 16.1.

The EVC2 gene is located on the short (p) arm of chromosome 4 between positions 16.2 and 16.1.

More precisely, the EVC2 gene is located from base pair 5,562,418 to base pair 5,709,547 on chromosome 4.

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 EVC2?

You and your healthcare professional may find the following resources about EVC2 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 EVC2 gene or gene products?

  • Ellis van Creveld syndrome 2 (limbin)
  • LBN
  • LBN_HUMAN
  • limbin

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 EVC2?

amino acid ; cell ; chromosome ; dwarfism ; embryo ; gene ; inherited ; mutation ; protein ; syndrome

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

References

  • Blair HJ, Tompson S, Liu YN, Campbell J, MacArthur K, Ponting CP, Ruiz-Perez VL, Goodship JA. Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus. BMC Biol. 2011 Feb 28;9:14. doi: 10.1186/1741-7007-9-14. (http://www.ncbi.nlm.nih.gov/pubmed/21356043?dopt=Abstract)
  • Dorn KV, Hughes CE, Rohatgi R. A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia. Dev Cell. 2012 Oct 16;23(4):823-35. doi: 10.1016/j.devcel.2012.07.004. Epub 2012 Sep 13. (http://www.ncbi.nlm.nih.gov/pubmed/22981989?dopt=Abstract)
  • Galdzicka M, Patnala S, Hirshman MG, Cai JF, Nitowsky H, Egeland JA, Ginns EI. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. Mol Genet Metab. 2002 Dec;77(4):291-5. (http://www.ncbi.nlm.nih.gov/pubmed/12468274?dopt=Abstract)
  • Morrell CH, Brant LJ. Modelling hearing thresholds in the elderly. Stat Med. 1991 Sep;10(9):1453-64. (http://www.ncbi.nlm.nih.gov/pubmed/1925173?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/132884)
  • Ruiz-Perez VL, Goodship JA. Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands. Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):341-51. doi: 10.1002/ajmg.c.30226. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19876929?dopt=Abstract)
  • Ruiz-Perez VL, Tompson SW, Blair HJ, Espinoza-Valdez C, Lapunzina P, Silva EO, Hamel B, Gibbs JL, Young ID, Wright MJ, Goodship JA. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. Am J Hum Genet. 2003 Mar;72(3):728-32. Epub 2003 Feb 4. (http://www.ncbi.nlm.nih.gov/pubmed/12571802?dopt=Abstract)
  • Sund KL, Roelker S, Ramachandran V, Durbin L, Benson DW. Analysis of Ellis van Creveld syndrome gene products: implications for cardiovascular development and disease. Hum Mol Genet. 2009 May 15;18(10):1813-24. doi: 10.1093/hmg/ddp098. Epub 2009 Feb 27. (http://www.ncbi.nlm.nih.gov/pubmed/19251731?dopt=Abstract)
  • Tompson SW, Ruiz-Perez VL, Blair HJ, Barton S, Navarro V, Robson JL, Wright MJ, Goodship JA. Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients. Hum Genet. 2007 Jan;120(5):663-70. Epub 2006 Sep 21. (http://www.ncbi.nlm.nih.gov/pubmed/17024374?dopt=Abstract)
  • Valencia M, Lapunzina P, Lim D, Zannolli R, Bartholdi D, Wollnik B, Al-Ajlouni O, Eid SS, Cox H, Buoni S, Hayek J, Martinez-Frias ML, Antonio PA, Temtamy S, Aglan M, Goodship JA, Ruiz-Perez VL. Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling. Hum Mutat. 2009 Dec;30(12):1667-75. doi: 10.1002/humu.21117. (http://www.ncbi.nlm.nih.gov/pubmed/19810119?dopt=Abstract)
  • Ye X, Song G, Fan M, Shi L, Jabs EW, Huang S, Guo R, Bian Z. A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial dysostosis. Hum Genet. 2006 Mar;119(1-2):199-205. Epub 2006 Jan 11. (http://www.ncbi.nlm.nih.gov/pubmed/16404586?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: December 2012
Published: July 21, 2014