EDN3 endothelin 3 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: EDN3provided by HGNC
Official Full Name: endothelin 3provided by HGNC
Primary source: HGNC:3178
Locus tag: RP4-614C15.1
See related: Ensembl:ENSG00000124205; HPRD:00570; MIM:131242; Vega:OTTHUMG00000032867
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ET3; ET-3; WS4B; HSCR4; PPET3
Summary: The protein encoded by this gene is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides involved in a variety of biological functions. The active form of this protein is a 21 amino acid peptide processed from the precursor protein. The active peptide is a ligand for endothelin receptor type B (EDNRB). The interaction of this endothelin with EDNRB is essential for development of neural crest-derived cell lineages, such as melanocytes and enteric neurons. Mutations in this gene and EDNRB have been associated with Hirschsprung disease (HSCR) and Waardenburg syndrome (WS), which are congenital disorders involving neural crest-derived cells. Four alternatively spliced transcript variants encoding three distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 20q13.2-q13.3

Sequence :: Chromosome: 20; NC_000020.10 (57875499..57901047)

See EDN3 in Epigenomics, MapViewer

Chromosome 20 - NC_000020.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

plasma levels of big ET-2, and big ET-3 are markedly increased in patients with end stage renal disease on hemodialysis
Title: Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease.
A novel missense mutation in EDN3 and a deletion mutation in DMD has been found in the same Indian family members affected with Waardenburg syndrome and Duchenne muscular dystrophy.
Title: Genetic analysis of an Indian family with members affected with Waardenburg syndrome and Duchenne muscular dystrophy.
These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence.
Title: Autocrine endothelin-3/endothelin receptor B signaling maintains cellular and molecular properties of glioblastoma stem cells.
ET-1 and the ET-1/ET-3 ratio are elevated in cirrhotic patients with portopulmonary hypertension (PPHT) and that ET-1 is associated with a poor outcome irrespective of PPHT.
Title: Portopulmonary hypertension and serum endothelin levels in hospitalized patients with cirrhosis.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Finding suggest that mutations in RET and NTRK3 acting together are necessary and sufficient for the appearance of Hirschsprung disease and that the EDN3 mutation acts as a phenotype modifier.
Title: Contribution of RET, NTRK3 and EDN3 to the expression of Hirschsprung disease in a multiplex family.
EDN3 may be considered as a common susceptibility gene for sporadic Hirschsprung disease in a low-penetrance fashion.
Title: New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.
EDN3, in contrast to EDN1 and EDN2, may act as natural tumour suppressor in the human mammary gland
Title: Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer.
Observational study of gene-disease association. (HuGE Navigator)
Title: A candidate gene study of obstructive sleep apnea in European Americans and African Americans.
Report on spanish cases of Waardenburg syndrome type 4 with novel mutations in EDN3 and SOX 10 genes.
Title: Genetic and phenotypic heterogeneity in two novel cases of Waardenburg syndrome type IV.

Submit: New GeneRIF Correction See all (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Congenital central hypoventilation

MIM: 209880

Genetic Testing Registry

Summary from GeneReviews: Congenital Central Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) is characterized by a classic presentation in newborns and a milder later-onset (LO-CCHS) presentation in toddlers, children, and adults. Classic CCHS presents in newborns as (1) apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; (2) autonomic nervous system dysregulation (ANSD); and (3) in some individuals, altered development of neural crest-derived structures (i.e., Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Individuals with CCHS who have been diagnosed early and ventilated conservatively and consistently throughout childhood have reached the age of 20 to 30 years. LO-CCHS manifests as nocturnal alveolar hypoventilation and mild ANSD. Individuals with LO-CCHS who were not identified until age 20 years or older have reached the age of 30 to 55 years.

Diagnosis Testing

Diagnosis of CCHS is established based on (1) clinical findings of alveolar hypoventilation and ANSD in the absence of primary pulmonary, cardiac, or neuromuscular disease, or a causative brain stem lesion that can account for the entire phenotype; and (2) identification of a disease-causing mutation in PHOX2B. Molecular genetic testing of PHOX2B, the only gene in which mutations are known to cause CCHS, is available clinically.

Genetic Counseling

CCHS is inherited in an autosomal dominant manner. Most individuals with CCHS are heterozygous for a de novo PHOX2B mutation; some have an affected parent and 5%-10% have an asymptomatic parent who has mosaicism for a PHOX2B mutation. Each child of an individual with CCHS has a 50% chance of inheriting the PHOX2B mutation; the risk to the offspring of an individual with mosaicism is 50% or lower. Prenatal testing for pregnancies at increased risk is possible if the causative mutation has been identified in an affected family member.

NHGRI GWAS Catalog

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Genome-wide association study of blood pressure and hypertension.

Interactions

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Products	Interactant	Other Gene	Source	Pubs
P14138	P23946	CMA1	HPRD	PubMed
P14138	P14091	CTSE	HPRD	PubMed
P14138	P25101	EDNRA	HPRD	PubMed
P14138	P24530	EDNRB	HPRD	PubMed
P14138	P23276	KEL	HPRD	PubMed

Pathways from BioSystems

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Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
Endothelins, organism-specific biosystem (from Pathway Interaction Database)
Endothelins, organism-specific biosystem
Endothelins
G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

General gene information

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Markers

STS-X52001 (e-PCR)
- UniSTS:43074

WI-17085 (e-PCR)
- UniSTS:82518

Edn3 (e-PCR), detects polymorphism
- UniSTS:142962

EDN3_1730 (e-PCR)
- UniSTS:277183

SHGC-132082 (e-PCR)
- UniSTS:183502

D20S1073 (e-PCR)
- UniSTS:78031

D2S2882 (e-PCR)
- UniSTS:10982

WI-18958 (e-PCR)
- UniSTS:53479

Genotypes

See EDN3 SNP Geneview Report
See EDN3 SNP Genotype Report
See EDN3 SNP Variation Viewer Report

Homology

Homologs of the EDN3 gene: The EDN3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

MGC15067, MGC61498

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
hormone activity	IDA Inferred from Direct Assay more info	PubMed
receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
NOT artery smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed
blood circulation	TAS Traceable Author Statement more info	PubMed
cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cell-cell signaling	TAS Traceable Author Statement more info	PubMed
inositol phosphate-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
melanocyte differentiation	IEA Inferred from Electronic Annotation more info
multicellular organismal development	TAS Traceable Author Statement more info	PubMed
neural crest cell migration	IEA Inferred from Electronic Annotation more info
neuron differentiation	IEA Inferred from Electronic Annotation more info
neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
peptide hormone secretion	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of heart rate	IDA Inferred from Direct Assay more info	PubMed
positive regulation of hormone secretion	IDA Inferred from Direct Assay more info	PubMed
positive regulation of leukocyte chemotaxis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of mitosis	IDA Inferred from Direct Assay more info	PubMed
regulation of developmental pigmentation	IEA Inferred from Electronic Annotation more info
regulation of systemic arterial blood pressure by endothelin	IDA Inferred from Direct Assay more info	PubMed
regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed
vasoconstriction	IDA Inferred from Direct Assay more info	PubMed
vein smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: endothelin-3

Names: endothelin-3; preproendothelin-3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008050.1 RefSeqGene

Range

5001..30549

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000114.2 → NP_000105.1 endothelin-3 isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

BC008876, J05081

Consensus CDS

CCDS13477.1

UniProtKB/Swiss-Prot

P14138

Related

ENSP00000360067, ENST00000371028

Conserved Domains (2) summary

pfam00322
Location:93 – 122
Blast Score: 156

Endothelin; Endothelin family

smart00272
Location:158 – 179
Blast Score: 101

END; Endothelin
NM_207032.1 → NP_996915.1 endothelin-3 isoform 2 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternative splice site in the coding region and lacks a segment in the 3' UTR compared to variant 1. The resulting isoform (2) has a distinct and shorter C-terminus, as compared to isoform 1.

Source sequence(s)

BC008876, BC053866

Consensus CDS

CCDS13479.1

UniProtKB/Swiss-Prot

P14138

Related

ENSP00000311854, OTTHUMP00000031421, ENST00000311585, OTTHUMT00000079920

Conserved Domains (2) summary

pfam00322
Location:93 – 122
Blast Score: 155

Endothelin; Endothelin family

smart00272
Location:158 – 179
Blast Score: 101

END; Endothelin
NM_207033.1 → NP_996916.1 endothelin-3 isoform 3 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an exon and uses an alternative splice site in the coding region compared to variant 1. The translation frame remains the same. The resulting isoform (3) lacks an internal region, as compared to isoform 1.

Source sequence(s)

BC008876, X52001

Consensus CDS

CCDS13478.1

UniProtKB/Swiss-Prot

P14138

Related

ENSP00000379015, OTTHUMP00000031422, ENST00000395654, OTTHUMT00000079921

Conserved Domains (2) summary

pfam00322
Location:93 – 122
Blast Score: 156

Endothelin; Endothelin family

smart00272
Location:158 – 179
Blast Score: 101

END; Endothelin
NM_207034.1 → NP_996917.1 endothelin-3 isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an additional fragment within the 3' UTR compared to variant 1. Both variants encode the same isoform (1).

Source sequence(s)

BC008876

Consensus CDS

CCDS13477.1

UniProtKB/Swiss-Prot

P14138

Related

ENSP00000337128, OTTHUMP00000031420, ENST00000337938, OTTHUMT00000079919

Conserved Domains (2) summary

pfam00322
Location:93 – 122
Blast Score: 156

Endothelin; Endothelin family

smart00272
Location:158 – 179
Blast Score: 101

END; Endothelin

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000020.10 Reference GRCh37.p10 Primary Assembly

Range

57875499..57901047

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000152.1 Alternate HuRef

Range

54662632..54688190

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018931.1 Alternate CHM1_1.0

Range

57845513..57871062

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01005965.1 (29574..55132)	None
genomic	AL035250.20 (31748..57296)	None
genomic	AMYH01012025.1 (49..25598)	None
genomic	AY444503.1	AAR16083.1
genomic	CH471077.2	EAW75434.1
		EAW75435.1
		EAW75436.1
		EAW75437.1
genomic	M25551.1	AAA52341.1
mRNA	BC008876.2	AAH08876.1
mRNA	BC053866.1	AAH53866.1
mRNA	BT007085.1	AAP35748.1
mRNA	DQ096281.1	AAZ03610.1
mRNA	J05081.1	AAA52405.1
mRNA	S50864.1	None
mRNA	S50866.1	None
mRNA	X52001.1	CAA36252.1
other-genetic	HQ447100.1	ADQ31587.1