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

Summary

Official Symbol: EDN3provided by HGNC
Official Full Name: endothelin 3provided by HGNC
Primary source: HGNC:HGNC:3178
See related: Ensembl:ENSG00000124205 MIM:131242; AllianceGenome:HGNC:3178
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. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
Expression: Biased expression in small intestine (RPKM 16.6), duodenum (RPKM 16.3) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.32

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (59300611..59325992)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (61083933..61109315)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (57875666..57901047)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue.
Title: Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue.
Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer.
Title: Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer.
The ratio of circulating endothelin-1 to endothelin-3 associated with TIMI risk and dynamic TIMI risk score in ST elevation acute myocardial infarction.
Title: The ratio of circulating endothelin-1 to endothelin-3 associated with TIMI risk and dynamic TIMI risk score in ST elevation acute myocardial infarction.
miR27a3p regulates the inhibitory influence of endothelin 3 on the tumorigenesis of papillary thyroid cancer cells.
Title: miR‑27a‑3p regulates the inhibitory influence of endothelin 3 on the tumorigenesis of papillary thyroid cancer cells.
Growth factor and receptor malfunctions associated with human genetic deafness.
Title: Growth factor and receptor malfunctions associated with human genetic deafness.
Insights into Endothelin-3 and Multiple Sclerosis.
Title: Insights into Endothelin-3 and Multiple Sclerosis.
Association of endothelin genetic variants and hospitalized infection complications in end-stage renal disease (ESRD) patients.
Title: Association of endothelin genetic variants and hospitalized infection complications in end-stage renal disease (ESRD) patients.
the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging, is reported.
Title: SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions.
genome-wide association studies in population of women in China: Data suggest that EDN3 (endothelin 3) and EDNRB (endothelin receptor type B) play important roles in the molecular mechanisms underlying cervical cancer.
Title: Genome-wide analysis of aberrant gene expression and methylation profiles reveals susceptibility genes and underlying mechanism of cervical cancer.
EDN3 expression in left internal mammary arteries depends on tissue harvesting technique.
Title: The comparison of traditional and modified harvesting techniques of left ınternal mammary artery regarding endothelin-1/2/3 expression and free flow capacity.

Submit: New GeneRIF Correction See all GeneRIFs (32)

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

Associated conditions

Description	Tests
Hirschsprung disease, susceptibility to, 4 MedGen: C3150975 OMIM: 613712 GeneReviews: Not available	Compare labs
Waardenburg syndrome type 4B MedGen: C2750457 OMIM: 613265 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of blood pressure and hypertension. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endothelin B receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables endothelin B receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables hormone activity	IBA Inferred from Biological aspect of Ancestor more info
enables hormone activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
NOT involved_in artery smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed
involved_in axon extension	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in blood circulation	TAS Traceable Author Statement more info	PubMed
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
involved_in intracellular calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular magnesium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in melanocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in neural crest cell migration	IEA Inferred from Electronic Annotation more info
involved_in neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide hormone secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of heart rate	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of hormone secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of leukocyte chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mitotic nuclear division	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of potassium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smooth muscle contraction	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of developmental pigmentation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of systemic arterial blood pressure by endothelin	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of systemic arterial blood pressure by endothelin	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in vasoconstriction	IDA Inferred from Direct Assay more info	PubMed
involved_in vein smooth muscle contraction	IBA Inferred from Biological aspect of Ancestor more info
involved_in vein smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: endothelin-3

Names: 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

5168..30549

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1381

mRNA and Protein(s)

NM_001302455.2 → NP_001289384.1 endothelin-3 isoform 4 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in the 3' terminal exon, which results in a frameshift and an early stop codon, compared to variant 4. The encoded isoform (4) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

BC008876, BC053866, DN989853

UniProtKB/TrEMBL

A0A2R8Y214

Related

ENSP00000493472.1, ENST00000644821.1

Conserved Domains (2) summary

smart00272
Location:158 → 179

END; Endothelin

pfam00322
Location:93 → 121

Endothelin; Endothelin family
NM_001302456.2 → NP_001289385.1 endothelin-3 isoform 5 preproprotein

See identical proteins and their annotated locations for NP_001289385.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an exon in the 3' coding region, which results in a frameshift and an early stop codon, compared to variant 4. The encoded isoform (5) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

BC008876, BC053866, DQ096281, X52001

Consensus CDS

CCDS77597.1

UniProtKB/TrEMBL

A0A2R8Y214, Q4FAT2

Related

ENSP00000360064.3, ENST00000371025.7

Conserved Domains (2) summary

smart00272
Location:158 → 179

END; Endothelin

pfam00322
Location:93 → 121

Endothelin; Endothelin family
NM_001424361.1 → NP_001411290.1 endothelin-3 isoform 6 preproprotein

Status: REVIEWED

Source sequence(s)

AL035250
NM_001424362.1 → NP_001411291.1 endothelin-3 isoform 7 preproprotein

Status: REVIEWED

Source sequence(s)

AL035250
NM_001424363.1 → NP_001411292.1 endothelin-3 isoform 8 preproprotein

Status: REVIEWED

Source sequence(s)

AL035250
NM_207032.3 → NP_996915.1 endothelin-3 isoform 2 preproprotein

See identical proteins and their annotated locations for NP_996915.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 4. The encoded isoform (2), is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

BC008876, BC053866

Consensus CDS

CCDS13479.1

UniProtKB/TrEMBL

A0A2R8Y214

Related

ENSP00000311854.7, ENST00000311585.11

Conserved Domains (2) summary

smart00272
Location:158 → 179

END; Endothelin

pfam00322
Location:93 → 121

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

See identical proteins and their annotated locations for NP_996916.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an exon in the 3' coding region and uses an alternate in-frame splice site in the 3' coding region, compared to variant 4. The encoded isoform (3) is shorter and has two distinct internal amino acids, compared to isoform 1.

Source sequence(s)

BC008876, BC053866, X52001

Consensus CDS

CCDS13478.1

UniProtKB/TrEMBL

A0A2R8Y214

Related

ENSP00000379015.3, ENST00000395654.3

Conserved Domains (2) summary

smart00272
Location:158 → 179

END; Endothelin

pfam00322
Location:93 → 121

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

See identical proteins and their annotated locations for NP_996917.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) encodes the longest isoform (1).

Source sequence(s)

BC008876

Consensus CDS

CCDS13477.1

UniProtKB/Swiss-Prot

E1P5I5, P14138, Q03229, Q7Z6D2, Q9UGT7

UniProtKB/TrEMBL

A0A2R8Y214

Related

ENSP00000337128.2, ENST00000337938.7

Conserved Domains (3) summary

PHA03418
Location:24 → 87

PHA03418; hypothetical E4 protein; Provisional

smart00272
Location:158 → 179

END; Endothelin

pfam00322
Location:93 → 121

Endothelin; Endothelin family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000020.11 Reference GRCh38.p14 Primary Assembly

Range

59300611..59325992

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011528655.3 → XP_011526957.1 endothelin-3 isoform X2

Conserved Domains (2) summary

smart00272
Location:158 → 179

END; Endothelin

pfam00322
Location:93 → 121

Endothelin; Endothelin family

RNA

XR_936513.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060944.1 Alternate T2T-CHM13v2.0

Range

61083933..61109315

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054323135.1 → XP_054179110.1 endothelin-3 isoform X2

RNA

XR_008485241.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_000114.2: Suppressed sequence

Description

NM_000114.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.