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EVC

EvC ciliary complex subunit 1

The EVC gene provides instructions for a protein crucial for normal growth and development, particularly bone and tooth formation, and is associated with conditions like Ellis-van Creveld syndrome. The EVC gene encodes a protein that plays a significant role in the development of bones and teeth, and is found within primary cilia, which are important for cellular signalling.

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, is essential for typical growth and development, particularly affecting the formation of bones and teeth. The protein produced from the EVC gene is located in primary cilia, which are microscopic, finger-like projections on cell surfaces that facilitate communication between cells. This gene's function is closely related to its neighbouring gene, EVC2, and they are thought to work together in key developmental pathways.

What the gene does

The EVC gene produces a protein whose precise molecular function is still being investigated, but it is understood to be vital for normal growth and development, especially of skeletal structures and teeth. The EVC protein localises to primary cilia, which are cellular organelles involved in critical signalling pathways. It is believed to help regulate the Sonic Hedgehog signalling pathway, which governs cell growth, cell specialisation, and the patterning of various body parts during development. This regulatory role of EVC in ciliary function underpins its importance in musculoskeletal development and overall growth.

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Chromosome location

The EVC gene is situated on the short arm of chromosome 4 at position 16.2, denoted as 4p16.2. It is located in close proximity to the EVC2 gene, and researchers suggest that these two genes may have coordinated functions.

Protein structure

The EVC protein consists of 992 amino acids. Its structure includes several disordered regions. Specifically, disordered regions are found at amino acids 66-105, 151-181, 825-854, and 930-992.

Key variants

Genetic variations, or variants, within the EVC gene can alter the protein's function, leading to various health conditions. More than 25 different pathogenic variants in EVC have been identified. These variants can disrupt the normal activity of the EVC protein or result in the production of an unusually short, non-functional protein.

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.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.528del
Deletion
 p.Ser177fs Pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.618-1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Curry-Hall syndrome
c.618-2A>G
single nucleotide variant
 - Pathogenic ★★☆☆ EVC-related disorder
c.653T>G
single nucleotide variant
 p.Leu218Ter Pathogenic/Likely pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.801+1G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Ellis-van Creveld syndrome
c.90_91insT
Insertion
 p.Ala31fs Pathogenic/Likely pathogenic ★★☆☆ Curry-Hall 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 Ellis-van Creveld syndrome, an inherited disorder characterised by short stature, abnormal nails and teeth, and heart defects. Another related condition, Weyers acrofacial dysostosis, is also linked to EVC variants. Weyers acrofacial dysostosis presents with similar but typically milder symptoms affecting the teeth, nails, and bones.

Inheritance pattern

Conditions caused by pathogenic EVC variants typically follow ar/ad inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

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

UK clinical status

The EVC gene is included in several NHS Genomic Medicine Service national test panels in the UK. It is assessed within panels for Foetal anomalies (R21), Neurological ciliopathies, Rare multisystem ciliopathy disorders, Skeletal ciliopathies, Skeletal dysplasia (R104), and Thoracic dystrophies, all listed as 'green' in the NHS Genomic England PanelApp, indicating strong evidence for its 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 making a protein that is important for normal growth and development, particularly for the formation of bones and teeth. It is involved in cellular signalling pathways, including the Sonic Hedgehog pathway, through its location in primary cilia.

What conditions are associated with variants in the EVC gene?

Pathogenic variants in the EVC gene are associated with Ellis-van Creveld syndrome, a condition characterised by dwarfism, abnormal nails and teeth, and heart defects. It can also cause Weyers acrofacial dysostosis, which has similar but typically milder symptoms.

How is Ellis-van Creveld syndrome inherited?

Ellis-van Creveld syndrome caused by EVC gene variants is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the pathogenic variant, one from each parent, to develop the condition. Parents who carry one copy are typically unaffected.

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 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .