EDN2

Chr 1

endothelin 2

Also known as: ET-2, ET2, PPET2

NCBI Gene: 1907ENSG00000127129UniProt: P20800

This gene encodes a member of the endothelin protein family of secretory vasoconstrictive peptides. The preproprotein is processed to a short mature form which functions as a ligand for the endothelin receptors that initiate intracellular signaling events. This gene product is involved in a wide range of biological processes, such as hypertension and ovulation. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

42
ClinVar variants
10
Pathogenic / LP
0.06
pLI score
0
Active trials
Clinical Summary— EDN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 28 VUS of 42 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.02LOEUF
pLI 0.060
Z-score 1.55
OE 0.39 (0.18–1.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.13Z-score
OE missense 0.97 (0.82–1.13)
108 obs / 111.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.18–1.02)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.82–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 3 / 7.6Missense obs/exp: 108 / 111.8Syn Z: 0.79

ClinVar Variant Classifications

42 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS28
Likely Benign3
Benign1
7
Pathogenic
3
Likely Pathogenic
28
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
0
24
4
0
28
Likely Benign
0
3
0
0
3
Benign
0
0
1
0
1
Total02715042

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ENDOTHELIN 2; EDN2
MIM #131241 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gram-negative intratumoral bacteria mediate lymph node metastasis through LPS-TLR4/MAPK signaling pathway in cervical cancer.
Liu Y et al.·J Infect
2025
CXCL8 is essential for cervical cancer cell acquired radioresistance and acts as a promising therapeutic target in cervical cancer.
Hu Q et al.·Sci Rep
2025
Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer.
Wiesmann F et al.·Breast Cancer Res
2009
Human notochordal cell transcriptome unveils potential regulators of cell function in the developing intervertebral disc.
Rodrigues-Pinto R et al.·Sci Rep
2018
Dissecting genetic factors affecting phenylephrine infusion rates during anesthesia: a genome-wide association study employing EHR data.
Zhang Y et al.·BMC Med
2019
Epigenome-wide methylation study identified two novel CpGs associated with T2DM risk and a network of co-methylated CpGs capable of patient's classifications.
Giri AK et al.·Hum Mol Genet
2023
Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea.
Chatsuriyawong S et al.·BMC Med Genomics
2013
Comprehensive analysis of androgen receptor splice variant target gene expression in prostate cancer.
Wüstmann N et al.·Biochim Biophys Acta Mol Cell Res
2026
EDNRA variants associate with smooth muscle mRNA levels, cell proliferation rates, and cystic fibrosis pulmonary disease severity.
Darrah R et al.·Physiol Genomics
2010
Genetic variance in nitric oxide synthase and endothelin genes among children with and without endothelial dysfunction.
Chatsuriyawong S et al.·J Transl Med
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated single-cell RNA and ATAC sequencing of B-cell lymphoma-3(Bcl3) and endothelin-2(Edn2) proteins as targets to prevent glaucoma progression.
Wang D et al.·Int J Biol Macromol
2025
A novel missense variant in endothelin-2 (EDN2) causes a growth and respiratory lethal syndrome in bovine.
Eusebi PG et al.·Anim Genet
2022🔓 Open Access
The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population.
Çınar MU et al.·PLoS One
2020🔓 Open Access
Cd9 Protects Photoreceptors from Injury and Potentiates Edn2 Expression.
Iwagawa T et al.·Invest Ophthalmol Vis Sci
2020🔓 Open Access
MicroRNA-124 Enhances Dopamine Receptor Expression and Neuronal Proliferation in Mouse Models of Parkinson's Disease via the Hedgehog Signaling Pathway by Targeting EDN2.
Wang J et al.·Neuroimmunomodulation
2019Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools