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EVC

EvC ciliary complex subunit 1

The EVC gene provides instructions for a protein critical for normal growth and development, particularly for bones and teeth, and is associated with conditions like Ellis-van Creveld syndrome. The EVC gene is involved in producing a protein that plays an important, though not fully understood, role in regulating developmental pathways.

Chromosome 4p16.2 AR/AD HGNC:3497 Tier C
EVC 4p16.2 p arm q arm 4

EVC is located on the short (p) arm of chromosome 4, at band 4p16.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 4 in the library →

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Clinical tests that include this

Carrier Screening panel
EVC is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The EVC gene, or EvC ciliary complex subunit 1, encodes a protein involved in fundamental processes of growth and development. This protein is particularly important for the proper formation of bones and teeth. It is located within primary cilia, which are small, finger-like projections on the surface of cells that act as cellular antennae, receiving and transmitting signals critical for development and tissue maintenance.

What the gene does

The protein produced from the EVC gene is situated in primary cilia, which are organelles essential for cell signalling. While its exact function is not fully understood, the EVC protein appears to be involved in regulating the Sonic Hedgehog signalling pathway. This pathway is crucial for various cellular processes, including cell growth, specialisation, and the patterning of many body parts during development. Coordinated activity between the EVC protein and the protein from the closely located EVC2 gene is thought to be important for their combined function in these developmental pathways.

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Chromosome location

The EVC gene is located on the short arm of chromosome 4 at position 16.2 (4p16.2). It is situated in close proximity to the EVC2 gene, and research suggests these two genes may have related and coordinated functions.

Protein structure

The EVC protein consists of 992 amino acids. Its structural characteristics include several disordered regions: amino acids 66-105, amino acids 151-181, amino acids 825-854, and amino acids 930-992. These regions may contribute to the protein's flexibility and its ability to interact with other molecules within the cell.

Key variants

Variants in the EVC gene can alter the function or production of the EVC protein, leading to a range of inherited conditions. These genetic changes can either disrupt the protein's normal activity or result in a protein that is abnormally small or non-functional. More than 25 different variants have been identified in this gene.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for EVC.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1098+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.1269_1278del
Deletion
 p.Gln424fs Pathogenic/Likely pathogenic ★★☆☆ Curry-Hall syndrome
c.1412_1413del
Microsatellite
 p.Arg471fs Pathogenic/Likely pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.1618del
Deletion
 p.Leu540fs Pathogenic/Likely pathogenic ★★☆☆ Curry-Hall syndrome
c.1652dup
Duplication
 p.Glu552fs Pathogenic/Likely pathogenic ★★☆☆ Curry-Hall syndrome
c.1662_1663del
Microsatellite
 p.Cys554_Asp555delinsTer Pathogenic/Likely pathogenic ★★☆☆ Curry-Hall syndrome
c.1750dup
Duplication
 p.Gln584fs Pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.2167C>T
single nucleotide variant
 p.Gln723Ter Pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.2382C>A
single nucleotide variant
 p.Tyr794Ter Pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.2752A>T
single nucleotide variant
 p.Lys918Ter Pathogenic/Likely pathogenic ★★☆☆ Ellis-van Creveld syndrome

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the EVC gene are primarily associated with skeletal dysplasias, including Ellis-van Creveld syndrome and Weyers acrofacial dysostosis. Ellis-van Creveld syndrome is typically inherited in an autosomal recessive pattern and is characterised by short stature, heart defects, and abnormalities of the nails and teeth. Weyers acrofacial dysostosis, often milder, can be caused by dominant variants and shares some clinical features affecting dental, nail, and bone development.

Inheritance pattern

Conditions caused by pathogenic EVC variants typically follow autosomal recessive or autosomal dominant inheritance.

Carrier frequency by population How common is heterozygous EVC carrier status across ancestry groups?

UK clinical status

The EVC gene is recognised within the NHS Genomic Medicine Service due to its association with several conditions. It is included on various R-number panels, indicating its clinical relevance in the UK. These include panels for DDG2P, Foetal anomalies (R21), Neurological ciliopathies, Rare multisystem ciliopathy disorders, Skeletal ciliopathies, Skeletal dysplasia (R104), and Thoracic dystrophies, all of which are classified as 'green' indicating strong evidence for gene-disease association.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Fetal anomalies · R21 NHS GMS → Skeletal dysplasia · R104 NHS GMS → DDG2P NHS GMS → Neurological ciliopathies NHS GMS → Skeletal ciliopathies NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the EVC gene responsible for?

The EVC gene provides instructions for a protein that plays an important role in growth and development, particularly for the formation of healthy bones and teeth. It is involved in cell signalling pathways, specifically within primary cilia.

What is Ellis-van Creveld syndrome?

Ellis-van Creveld syndrome is an inherited disorder caused by variants in genes like EVC. It is characterised by short stature, heart abnormalities, and specific features affecting the nails and teeth. It is typically inherited in an autosomal recessive manner.

How can I find out if I am a carrier for an EVC variant?

Carrier screening tests can identify individuals who carry a variant in the EVC gene. If you have a family history of Ellis-van Creveld syndrome or related conditions, or if you are planning a family, you may wish to discuss carrier screening options with a genetic counsellor or healthcare provider.

References

  1. Blair HJ, Tompson S, Liu YN. Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus. BMC biology. 2011. PMID: 21356043
  2. Sund KL, Roelker S, Ramachandran V. Analysis of Ellis van Creveld syndrome gene products: implications for cardiovascular development and disease. Human molecular genetics. 2009. PMID: 19251731
  3. Valencia M, Lapunzina P, Lim D. Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling. Human mutation. 2009. PMID: 19810119
  4. Ruiz-Perez VL, Goodship JA. Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands. American journal of medical genetics. Part C, Seminars in medical genetics. 2009. PMID: 19876929
  5. Tompson SW, Ruiz-Perez VL, Blair HJ. Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients. Human genetics. 2007. PMID: 17024374
  6. Ruiz-Perez VL, Blair HJ, Rodriguez-Andres ME. Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia. Development (Cambridge, England). 2007. PMID: 17660199
  7. Ruiz-Perez VL, Tompson SW, Blair HJ. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. American journal of human genetics. 2003. PMID: 12571802
  8. Ruiz-Perez VL, Ide SE, Strom TM. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nature genetics. 2000. PMID: 10700184
  9. Howard TD, Guttmacher AE, McKinnon W. Autosomal dominant postaxial polydactyly, nail dystrophy, and dental abnormalities map to chromosome 4p16, in the region containing the Ellis-van Creveld syndrome locus. American journal of human genetics. 1997. PMID: 9399901
  10. Morrell CH, Brant LJ. Modelling hearing thresholds in the elderly. Statistics in medicine. 1991. PMID: 1925173
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .