EDN2

Chr 1

endothelin 2

Also known as: ET-2, ET2, PPET2

Endothelin-2 is a secreted vasoconstrictor peptide that binds to endothelin receptors and regulates vascular tone and various physiological processes including blood pressure control. Mutations in EDN2 cause Feingold syndrome type 2, an autosomal dominant developmental disorder characterized by microcephaly, limb malformations (particularly digital anomalies), and gastrointestinal atresias. The gene shows tolerance to loss-of-function variants, suggesting the pathogenic variants may act through alternative mechanisms.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.02
Clinical SummaryEDN2
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.060
Z-score 1.55
OE 0.39 (0.181.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.13Z-score
OE missense 0.97 (0.821.13)
108 obs / 111.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.181.02)
00.351.4
Missense OE0.97 (0.821.13)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 3 / 7.6Missense obs/exp: 108 / 111.8Syn Z: 0.79
DN
0.6552th %ile
GOF
0.4972th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EDN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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