EDNRB

endothelin receptor type B, the group of Endothelin receptors

Basic information

Region (hg38): 13:77895480-77975529

Previous symbols: [ "HSCR2", "HSCR" ]

Links

ENSG00000136160 ∙ NCBI:1910 ∙ OMIM:131244 ∙ HGNC:3180 ∙ Uniprot:P24530 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Waardenburg syndrome type 4A (Strong), mode of inheritance: AD
• Waardenburg syndrome type 4A (Strong), mode of inheritance: AR
• ABCD syndrome (Definitive), mode of inheritance: AD
• Waardenburg syndrome type 2 (Supportive), mode of inheritance: AD
• Waardenburg-Shah syndrome (Supportive), mode of inheritance: AD
• Waardenburg syndrome type 4A (Moderate), mode of inheritance: Semidominant
• Hirschsprung disease, susceptibility to, 2 (Limited), mode of inheritance: Unknown
• Waardenburg syndrome type 4A (Strong), mode of inheritance: AR
• Waardenburg syndrome type 4A (Limited), mode of inheritance: AD
• Waardenburg syndrome type 4A (Moderate), mode of inheritance: AR
• Waardenburg syndrome type 4A (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Waardenburg syndrome type 4A; ABCD syndrome; Hirschsprung disease, susceptibility to, 2	AD/AR	Audiologic/Otolaryngologic; Gastrointestinal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg, Hirschsprung disease) may allow prompt treatment	Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Ophthalmologic	7264803; 8001158; 8634719; 7778600; 10528251; 11484199; 11891690; 19764031

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EDNRB gene.

• not provided (160 variants)
• Hirschsprung disease, susceptibility to, 2 (74 variants)
• not specified (30 variants)
• Waardenburg syndrome type 4A (19 variants)
• Inborn genetic diseases (11 variants)
• Waardenburg syndrome (4 variants)
• ABCD syndrome;Hirschsprung disease, susceptibility to, 2;Waardenburg syndrome type 4A (4 variants)
• EDNRB-related condition (3 variants)
• Hirschsprung Disease, Recessive (3 variants)
• Hearing impairment;Aganglionosis, total intestinal (2 variants)
• Hearing impairment (2 variants)
• ABCD syndrome (2 variants)
• Aganglionic megacolon (2 variants)
• Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant (1 variants)
• Hearing loss, autosomal recessive (1 variants)
• Waardenburg syndrome type 2A (1 variants)
• EDNRB-Related Disorders (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDNRB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	22	2	27
missense		2	86	4		92
nonsense	4	2	2			8
start loss						0
frameshift	3	5	3			11
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	6				9
splice region			2	2		4
non coding			48	21	12	81
Total	10	15	143	47	14

Highest pathogenic variant AF is 0.00000659

Variants in EDNRB

This is a list of pathogenic ClinVar variants found in the EDNRB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-77895535-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77895620-G-A		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77895737-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77895748-C-T		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77895774-T-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77895845-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77895891-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77895908-T-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 15, 2018)
13-77895942-C-A		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77895981-T-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896033-G-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896035-G-A		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77896136-A-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77896145-T-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896153-G-A		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77896159-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896294-C-T		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896340-A-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77896356-T-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896416-T-C		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77896433-G-A		not specified • Hirschsprung disease, susceptibility to, 2	Benign/Likely benign (Mar 04, 2019)
13-77896538-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 12, 2018)
13-77896568-G-T		not specified	Uncertain significance (May 21, 2015)
13-77896600-A-G		Hirschsprung disease, susceptibility to, 2	Uncertain significance (Jan 13, 2018)
13-77896654-T-C		Hirschsprung disease, susceptibility to, 2	Benign/Likely benign (Jul 05, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDNRB	protein_coding	protein_coding	ENST00000377211	8	24288

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00924	0.990	125588	0	8	125596	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	236	293	0.805	0.0000145	3437
Missense in Polyphen		31	68.129	0.45502		857
Synonymous	0.729	106	116	0.914	0.00000607	1072
Loss of Function	3.07	8	24.3	0.329	0.00000119	286

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000907	0.0000906
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:7536888}.
• Disease: DISEASE: Waardenburg syndrome 4A (WS4A) [MIM:277580]: A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease). {ECO:0000269|PubMed:12189494, ECO:0000269|PubMed:8634719}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hirschsprung disease 2 (HSCR2) [MIM:600155]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269|PubMed:11471546, ECO:0000269|PubMed:28236341, ECO:0000269|PubMed:8001158, ECO:0000269|PubMed:8630503, ECO:0000269|PubMed:8852660}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: ABCD syndrome (ABCDS) [MIM:600501]: An autosomal recessive syndrome characterized by albinism, black lock at temporal occipital region, bilateral deafness, aganglionosis of the large intestine and total absence of neurocytes and nerve fibers in the small intestine. {ECO:0000269|PubMed:11891690}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Heterozygous mutations in EDNRB may be responsible for Waardenburg syndrome 2, an autosomal dominant disorder characterized by sensorineural deafness and pigmentary disturbances. {ECO:0000269|PubMed:28236341}.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Endothelin Pathways;Peptide GPCRs;GPCRs, Class A Rhodopsin-like;Prostaglandin Synthesis and Regulation;Signaling by GPCR;Signal Transduction;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;ion channels and their functional role in vascular endothelium;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;chrebp regulation by carbohydrates and camp;role of -arrestins in the activation and targeting of map kinases;activation of camp-dependent protein kinase pka;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);roles of arrestin dependent recruitment of src kinases in gpcr signaling;GPCR ligand binding;-arrestins in gpcr desensitization;G alpha (q) signalling events;GPCR downstream signalling;Endothelins (Consensus)

Recessive Scores

• pRec: 0.729

Intolerance Scores

• loftool: 0.360
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.801
• hipred: Y
• hipred_score: 0.761
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.584

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ednrb
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: ednrba
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neural crest cell migration;positive regulation of protein phosphorylation;regulation of pH;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;negative regulation of adenylate cyclase activity;phospholipase C-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;nervous system development;peripheral nervous system development;posterior midgut development;aging;regulation of blood pressure;positive regulation of cell population proliferation;negative regulation of neuron maturation;response to organic cyclic compound;vein smooth muscle contraction;sensory perception of pain;calcium-mediated signaling;cGMP-mediated signaling;melanocyte differentiation;regulation of fever generation;negative regulation of cellular protein metabolic process;enteric smooth muscle cell differentiation;positive regulation of urine volume;positive regulation of renal sodium excretion;epithelial fluid transport;vasoconstriction;vasodilation;negative regulation of apoptotic process;macrophage chemotaxis;response to pain;enteric nervous system development;regulation of epithelial cell proliferation;regulation of sensory perception of pain;positive regulation of penile erection;cellular response to lipopolysaccharide;endothelin receptor signaling pathway;response to endothelin
• Cellular component: plasma membrane;integral component of plasma membrane;nuclear membrane;membrane raft
• Molecular function: endothelin receptor activity;protein binding;peptide hormone binding;type 1 angiotensin receptor binding