EVC

Chr 4ADAR

EvC ciliary complex subunit 1

Also known as: DWF-1, EVC1, EVCL

NCBI Gene: 2121 ENSG00000072840 UniProt: P57679 OMIM: 604831

The protein is a component of the EvC complex that positively regulates ciliary Hedgehog signaling and is involved in endochondral growth and skeletal development. Mutations cause Ellis-van Creveld syndrome and Weyers acrofacial dysostosis, both skeletal dysplasias affecting limb and craniofacial development. Inheritance is autosomal recessive for Ellis-van Creveld syndrome and autosomal dominant for Weyers acrofacial dysostosis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Weyers acrofacial dysostosisMIM #193530

Ellis-van Creveld syndromeMIM #225500

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Ellis-van Creveld syndrome · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.06

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — EVC

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.000

Z-score 1.17

OE 0.83 (0.65–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.25Z-score

OE missense 1.16 (1.08–1.24)

598 obs / 517.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.65–1.06)

0≤0.351.4

Missense OE?1.16 (1.08–1.24)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 43 / 52.1Missense obs/exp: 598 / 517.7Syn Z: -2.42

Background carrier burden — how many people carry a rare variant somewhere in EVC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 31

1,520 rare PASS variants

Rare truncating (LoF)

1 in 630

254 rare PASS variants

Rare synonymous (reference)

1 in 67

662 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EVC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 46	1 in 590
South Asian	~43k	1 in 28	1 in 770
Remaining (unassigned)	~30k	1 in 30	1 in 670
European (Finnish)	~27k	1 in 62	1 in 980
Admixed American	~22k	1 in 27	1 in 440
African / African American	~21k	1 in 20	1 in 520
East Asian	~20k	1 in 36	1 in 700
Ashkenazi Jewish	~13k	1 in 100	1 in 1,200
Middle Eastern	~2,884	1 in 23	1 in 410

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 21 coding exons well covered in gnomAD exomes; exons 1, 6 marginal. Genomes: all 21.? see exons ↓