EDN1

endothelin 1, the group of Endothelins

Basic information

Region (hg38): 6:12290360-12297194

Links

ENSG00000078401 ∙ NCBI:1906 ∙ OMIM:131240 ∙ HGNC:3176 ∙ Uniprot:P05305 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• auriculocondylar syndrome 1 (Strong), mode of inheritance: AR
• question mark ears, isolated (Strong), mode of inheritance: AD
• auriculocondylar syndrome (Supportive), mode of inheritance: AD
• question mark ears, isolated (Limited), mode of inheritance: AD
• auriculocondylar syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Question-mark ears, isolated; Auriculocondylar Syndrome 3	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial	24268655
Conductive hearing loss has been described in one individual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EDN1 gene.

• not provided (25 variants)
• Inborn genetic diseases (10 variants)
• Auriculocondylar syndrome 3 (2 variants)
• Question mark ears, isolated (1 variants)
• High density lipoprotein cholesterol level quantitative trait locus 7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDN1 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	3	6
missense			15	1	2	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					8	8
Total	0	0	15	4	13

Variants in EDN1

This is a list of pathogenic ClinVar variants found in the EDN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-12290675-C-A		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
6-12290701-C-T			Likely benign (Dec 31, 2019)
6-12290879-T-C			Benign (May 11, 2021)
6-12292295-G-A			Benign (May 12, 2021)
6-12292354-T-G			Likely benign (Aug 17, 2023)
6-12292365-C-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
6-12292365-C-T		Inborn genetic diseases	Uncertain significance (Nov 22, 2023)
6-12292366-G-A			Benign (Sep 23, 2022)
6-12292366-G-T		EDN1-related disorder	Likely benign (May 22, 2019)
6-12292382-G-A			Benign (Jul 26, 2023)
6-12292413-G-T		Inborn genetic diseases	Uncertain significance (Jan 05, 2022)
6-12292417-C-T		EDN1-related disorder	Benign (Dec 31, 2019)
6-12292444-G-A			Likely benign (Dec 24, 2021)
6-12292460-G-C		Question mark ears, isolated	Uncertain significance (Jul 03, 2022)
6-12292464-G-A			Uncertain significance (Mar 15, 2017)
6-12292467-T-A		Question mark ears, isolated	Pathogenic (Dec 05, 2013)
6-12292506-C-A		Auriculocondylar syndrome 3	Pathogenic (Dec 05, 2013)
6-12292507-C-T		EDN1-related disorder	Likely benign (Mar 01, 2019)
6-12292539-G-T			Benign (May 11, 2021)
6-12293904-T-C			Benign (May 11, 2021)
6-12293922-TTC-T			Benign (Mar 23, 2023)
6-12293945-G-A			Likely benign (Sep 10, 2023)
6-12293953-G-A			Likely benign (Dec 31, 2019)
6-12293956-T-G		Question mark ears, isolated	Pathogenic (Dec 05, 2013)
6-12293978-A-G		Auriculocondylar syndrome 3	Pathogenic (Dec 05, 2013)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDN1	protein_coding	protein_coding	ENST00000379375	5	6832

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.455	0.540	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.169	113	118	0.956	0.00000660	1384
Missense in Polyphen		21	35.185	0.59685		427
Synonymous	-0.482	47	43.0	1.09	0.00000255	379
Loss of Function	2.33	2	9.91	0.202	4.19e-7	135

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endothelins are endothelium-derived vasoconstrictor peptides.
• Disease: DISEASE: Auriculocondylar syndrome 3 (ARCND3) [MIM:615706]: A craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. {ECO:0000269|PubMed:24268655}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Endothelin Pathways;Melatonin metabolism and effects;Photodynamic therapy-induced HIF-1 survival signaling;Lung fibrosis;Prostaglandin Synthesis and Regulation;Signaling by GPCR;Signal Transduction;hypoxia-inducible factor in the cardivascular system;g-protein signaling through tubby proteins;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;corticosteroids and cardioprotection;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;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;nfat and hypertrophy of the heart ;role of -arrestins in the activation and targeting of map kinases;activation of camp-dependent protein kinase pka;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);roles of arrestin dependent recruitment of src kinases in gpcr signaling;GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;activation of pkc through g-protein coupled receptors;GPCR signaling-G alpha s PKA and ERK;-arrestins in gpcr desensitization;EGFR-dependent Endothelin signaling events;GPCR signaling-G alpha i;G alpha (q) signalling events;GPCR downstream signalling;AP-1 transcription factor network;HIF-1-alpha transcription factor network;Endothelins (Consensus)

Recessive Scores

• pRec: 0.751

Intolerance Scores

• loftool: 0.183
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.180
• hipred: N
• hipred_score: 0.450
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.521

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Edn1
• Phenotype: normal 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); 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); embryo phenotype; renal/urinary system phenotype; skeleton 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); digestive/alimentary phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: edn1
• Affected structure: hyohyoideus
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;prostaglandin biosynthetic process;branching involved in blood vessel morphogenesis;in utero embryonic development;histamine secretion;regulation of systemic arterial blood pressure by endothelin;regulation of pH;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;protein kinase C-activating G protein-coupled receptor signaling pathway;cell-cell signaling;heart development;respiratory gaseous exchange;body fluid secretion;positive regulation of cell population proliferation;dorsal/ventral pattern formation;response to ozone;multicellular organism aging;positive regulation of heart rate;regulation of signaling receptor activity;positive regulation of endothelial cell migration;positive regulation of cardiac muscle hypertrophy;regulation of glucose transmembrane transport;positive regulation of receptor biosynthetic process;neural crest cell development;phosphatidylinositol 3-kinase signaling;response to activity;artery smooth muscle contraction;vein smooth muscle contraction;regulation of vasoconstriction;sensory perception of pain;calcium-mediated signaling;peptide hormone secretion;nitric oxide transport;negative regulation of blood coagulation;positive regulation of cell migration;neutrophil chemotaxis;phospholipase D-activating G protein-coupled receptor signaling pathway;negative regulation of cellular protein metabolic process;positive regulation of prostaglandin secretion;response to lipopolysaccharide;response to testosterone;negative regulation of smooth muscle cell apoptotic process;response to prostaglandin F;response to nicotine;cellular response to drug;positive regulation of urine volume;positive regulation of renal sodium excretion;response to muscle stretch;epithelial fluid transport;vasoconstriction;protein kinase C deactivation;middle ear morphogenesis;positive regulation of odontogenesis;superoxide anion generation;rhythmic excitation;response to amino acid;positive regulation of MAP kinase activity;positive regulation of JUN kinase activity;response to leptin;leukocyte activation;positive regulation of nitric oxide biosynthetic process;positive regulation of cell size;positive regulation of mitotic nuclear division;positive regulation of transcription by RNA polymerase II;positive regulation of smooth muscle contraction;positive regulation of hormone secretion;negative regulation of hormone secretion;inositol phosphate-mediated signaling;positive regulation of smooth muscle cell proliferation;positive regulation of DNA-binding transcription factor activity;cartilage development;positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway;negative regulation of nitric-oxide synthase biosynthetic process;membrane depolarization;regulation of sensory perception of pain;maternal process involved in parturition;positive regulation of sarcomere organization;positive regulation of prostaglandin-endoperoxide synthase activity;positive regulation of cell growth involved in cardiac muscle cell development;positive regulation of chemokine-mediated signaling pathway;cellular response to calcium ion;cellular response to interferon-gamma;cellular response to interleukin-1;cellular response to tumor necrosis factor;cellular response to peptide hormone stimulus;cellular response to glucocorticoid stimulus;cellular response to mineralocorticoid stimulus;cellular response to fatty acid;cellular response to hypoxia;response to dexamethasone;cellular response to transforming growth factor beta stimulus;positive regulation of neutrophil chemotaxis;positive regulation of NIK/NF-kappaB signaling;response to salt;positive regulation of vascular smooth muscle cell proliferation
• Cellular component: extracellular region;extracellular space;cytoplasm;transport vesicle;Weibel-Palade body;basal part of cell;rough endoplasmic reticulum lumen
• Molecular function: cytokine activity;hormone activity;protein binding;endothelin A receptor binding;endothelin B receptor binding