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EVC2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

EVC2 gene

The EVC2 gene encodes a protein located in primary cilia that modulates Sonic Hedgehog signaling; mutations in both copies cause Ellis‑van Creveld syndrome, while single‑copy mutations cause the milder Weyers acrofacial dysostosis.

Overview

The EVC2 gene provides instructions for making a protein whose precise function is unknown, but it appears essential for normal growth and development, especially of bones and teeth. The EVC2 protein is found in primary cilia—microscopic, finger‑like projections on the cell surface that participate in signaling pathways transmitting information between cells. In particular, the EVC2 protein is thought to help regulate the Sonic Hedgehog pathway, which influences cell growth, specialization, and the patterning of many body parts.

EVC2 and the nearby EVC gene reside close together on chromosome 4, and researchers believe their activities may be coordinated.

Health Conditions Related to Genetic Changes

Ellis‑van Creveld syndrome

More than 30 mutations in the EVC2 gene have been identified as causes of Ellis‑van Creveld syndrome, an inherited disorder characterized by dwarfism, abnormal nails and teeth, and heart defects. The pathogenic mutations occur in both copies of the EVC2 gene in each cell, typically producing an abnormally small, nonfunctional version of the protein. Although the exact mechanism is unclear, loss of EVC2 function is believed to impair Sonic Hedgehog signaling during embryonic development, leading to abnormal bone growth and cardiac anomalies.

Weyers acrofacial dysostosis

At least three mutations in the EVC2 gene cause Weyers acrofacial dysostosis, a condition affecting teeth, nails, and bones. Its signs and symptoms resemble those of Ellis‑van Creveld syndrome but are generally milder. These mutations occur in a single copy of the EVC2 gene and alter a single amino‑acid near the protein’s C‑terminus, likely producing a shortened, malfunctioning protein. The defective protein is thought to interfere with Sonic Hedgehog signaling in the developing embryo, disrupting normal formation of teeth, nails, and bones.

Other Names for This Gene

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

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

  • Tests of EVC2

Scientific Articles on PubMed

  • PubMed

Catalog of Genes and Diseases from OMIM

  • EVC CILIARY COMPLEX SUBUNIT 2; EVC2

Gene and Variant Databases

  • NCBI Gene
  • ClinVar

Genomic Location

The EVC2 gene is located on chromosome 4.

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.
  • 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.
  • 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. doi: 10.1016/s1096-7192(02)00178-6.
  • Morrell CH, Brant LJ. Modelling hearing thresholds in the elderly. Stat Med. 1991 Sep;10(9):1453‑64. doi: 10.1002/sim.4780100912.
  • 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.
  • 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. doi: 10.1086/368063.
  • 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.
  • 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. doi: 10.1007/s00439-006-0237-7.
  • 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.
  • 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. doi: 10.1007/s00439-005-0129-2.

Frequently Asked Questions

Ellis-van Creveld syndrome, caused by mutations in both copies of the EVC2 gene, is more severe, characterized by dwarfism, significant heart defects, abnormal nails and teeth, and often extra fingers or toes. Weyers acrofacial dysostosis, caused by a mutation in only one copy of the EVC2 gene, is milder, primarily affecting teeth, nails, and bones, but typically without dwarfism or major heart defects.
Children with Ellis-van Creveld syndrome require a multidisciplinary approach involving pediatricians, cardiologists for heart defects, orthopedic specialists for skeletal issues, dentists for dental anomalies, and potentially other specialists. Regular monitoring for heart function, bone growth, and dental health is crucial, often starting from infancy.
The inheritance pattern depends on whether you have one or two mutated copies of the EVC2 gene. If you have Weyers acrofacial dysostosis (one mutated copy), each child has a 50% chance of inheriting that mutation and developing Weyers. If both parents carry one mutated copy, each child has a 25% chance of inheriting two mutated copies and developing the more severe Ellis-van Creveld syndrome, a 50% chance of inheriting one mutated copy and developing Weyers, and a 25% chance of inheriting no mutations.
Yes, treatment is symptomatic and supportive. Dental issues may require orthodontic work or specialized dental care. Skeletal problems, particularly in Ellis-van Creveld syndrome, might involve orthopedic interventions or physical therapy. Cardiac defects, if present, are managed by a cardiologist and may require medication or surgical repair depending on their severity.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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