EDNRB

Chr 13ARAD

endothelin receptor type B

Also known as: ABCDS, ET-B, ET-BR, ETB, ETB1, ETBR, ETRB, HSCR

NCBI Gene: 1910ENSG00000136160UniProt: P24530

The protein encoded by this gene is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. Studies suggest that the multigenic disorder, Hirschsprung disease type 2, is due to mutations in the endothelin receptor type B gene. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

Primary Disease Associations & Inheritance

?ABCD syndromeMIM #600501
AR
{Hirschsprung disease, susceptibility to, 2}MIM #600155
AD
Waardenburg syndrome, type 4AMIM #277580
ADAR
453
ClinVar variants
115
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— EDNRB
🧬
Gene-Disease Validity (ClinGen)
Waardenburg syndrome type 4A · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
115 Pathogenic / Likely Pathogenic· 229 VUS of 453 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.59LOEUF
pLI 0.009
Z-score 3.07
OE 0.33 (0.19–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.18Z-score
OE missense 0.81 (0.72–0.90)
236 obs / 293.0 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.0.33 (0.19–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.72–0.90)
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.0.91
0≤1.21.6
LoF obs/exp: 8 / 24.3Missense obs/exp: 236 / 293.0Syn Z: 0.73

ClinVar Variant Classifications

453 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic91
Likely Pathogenic24
VUS229
Likely Benign76
Benign14
Conflicting19
91
Pathogenic
24
Likely Pathogenic
229
VUS
76
Likely Benign
14
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
2
84
0
91
Likely Pathogenic
16
4
4
0
24
VUS
2
163
60
4
229
Likely Benign
0
5
31
40
76
Benign
0
0
12
2
14
Conflicting
—19
Total2317419146453

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

View in ClinVar →

Protein Context — Lollipop Plot

EDNRB · protein map & ClinVar variants

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

Gene2Phenotype Curations

EDNRB-related Waardenburg syndrome

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
SkinEar
G2P ↗
splice region variantframeshift variantstop gainedmissense variantwhole partial gene deletion

EDNRB-related Waardenburg syndrome with Hirschsprung

definitive
ARLoss Of FunctionAltered Gene Product Structure
Dev. DisordersSkinEar
G2P ↗
missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?ABCD syndrome

MIM #600501

Molecular basis of disorder known

Autosomal recessive

{Hirschsprung disease, susceptibility to, 2}

MIM #600155

Molecular basis of disorder known

Autosomal dominant

Waardenburg syndrome, type 4A

MIM #277580

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — EDNRB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung.
Schupp JC et al.·Circulation
2021
Review and update of mutations causing Waardenburg syndrome.
Pingault V et al.·Hum Mutat
2010Review
Multiomic and clinical analysis of multiply recurrent meningiomas reveals risk factors, underlying biology, and insights into evolution.
Pugazenthi S et al.·Sci Adv
2024
Genetics of Hirschsprung disease.
Parisi MA et al.·Curr Opin Pediatr
2000Review
Novel genetic determinants contribute to hearing loss in a central European cohort with enlarged vestibular aqueduct.
Bernardinelli E et al.·Mol Med
2025Cohort
The enteric nervous system.
Sasselli V et al.·Dev Biol
2012
Expression and regulation network of BLNK in CP/CPPS in animal, cell model and clinical samples.
Yu P et al.·Inflammation
2025Functional
Clinical relationship between EDN-3 gene, EDNRB gene and Hirschsprung's disease.
Duan XL et al.·World J Gastroenterol
2003
The clinical and genetic research of Waardenburg syndrome type I and II in Chinese families.
Liu Q et al.·Int J Pediatr Otorhinolaryngol
2020
RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling.
Widowati T et al.·Eur J Hum Genet
2016Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ednrb-driven ET-1/RXFP1 underlies TXA-induced exacerbation of acute cartilage injury-related PTOA.
Li M et al.·Biochem Biophys Res Commun
2026
Nicotinamide Counteracts the Detrimental Effect of Endothelin-1 on Uterine Decidualization During Early Pregnancy by Influencing EDNRB.
Wang Y et al.·Cells
2025🔓 Open Access
Joint disruption of Ret and Ednrb transcription shifts cell fate trajectories in the enteric nervous system in Hirschsprung disease.
Fine RD et al.·Proc Natl Acad Sci U S A
2025
Endothelin receptor antagonists target EDNRB and modulate the progression of idiopathic pulmonary fibrosis via anoikis-related genes.
Ning P et al.·Front Med (Lausanne)
2025🔓 Open Access
The Impact of Mutant EDNRB on the Two-End Black Coat Color Phenotype in Chinese Local Pigs.
Huang M et al.·Animals (Basel)
2025🔓 Open Access
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