EDNRB

Chr 13ARAD

endothelin receptor type B

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

This gene encodes endothelin receptor type B, a G protein-coupled receptor that binds endothelin peptides and activates phosphatidylinositol-calcium signaling pathways. Mutations cause Hirschsprung disease type 2 and Waardenburg syndrome type 4A, conditions affecting enteric nervous system development and neural crest cell migration respectively. The gene shows both autosomal recessive and autosomal dominant inheritance patterns depending on the associated phenotype.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.593 OMIM phenotypes
Clinical SummaryEDNRB
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.009
Z-score 3.07
OE 0.33 (0.190.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.18Z-score
OE missense 0.81 (0.720.90)
236 obs / 293.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.190.59)
00.351.4
Missense OE0.81 (0.720.90)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 8 / 24.3Missense obs/exp: 236 / 293.0Syn Z: 0.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEDNRB-related Waardenburg syndromeLOFAD
definitiveEDNRB-related Waardenburg syndrome with HirschsprungLOFAR
DN
0.77top 25%
GOF
0.79top 25%
LOF
0.2775th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median
LOF1 literature citation

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.

Literature Evidence

LOFNovel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's diseasePMID:8852658

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

ClinVar Variant Classifications

0 submitted variants 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.

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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