EDNRA

endothelin receptor type A, the group of Endothelin receptors

Basic information

Region (hg38): 4:147480917-147544954

Links

ENSG00000151617 ∙ NCBI:1909 ∙ OMIM:131243 ∙ HGNC:3179 ∙ Uniprot:P25101 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mandibulofacial dysostosis with alopecia (Supportive), mode of inheritance: AD
• mandibulofacial dysostosis with alopecia (Strong), mode of inheritance: AD
• mandibulofacial dysostosis with alopecia (Definitive), mode of inheritance: AD
• mandibulofacial dysostosis with alopecia (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mandibulofacial dysostosis with alopecia	AD	Audiologic/Otolaryngologic	Among other features, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Ophthalmologic	16116593; 20583178; 25772936

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDNRA 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			2	16	3	21
missense			32		2	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding				9	16	25
Total	0	0	34	25	21

Variants in EDNRA

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

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

Position	Type	Phenotype	Significance	ClinVar
4-147481217-G-A		Migraine, resistance to	protective (May 22, 2001)
4-147485381-T-C			Benign (May 11, 2021)
4-147485705-A-G		Migraine with or without aura, susceptibility to, 1;Mandibulofacial dysostosis with alopecia	Benign/Likely benign (Jan 12, 2024)
4-147485765-A-G			Likely benign (Nov 28, 2022)
4-147485769-C-A			Uncertain significance (Oct 26, 2023)
4-147485779-A-G			Uncertain significance (Jun 06, 2023)
4-147485824-T-C			Uncertain significance (May 01, 2022)
4-147485860-C-A			Uncertain significance (Sep 26, 2022)
4-147485870-C-T			Likely benign (Jul 17, 2023)
4-147485890-C-T		Inborn genetic diseases	Uncertain significance (May 13, 2024)
4-147485914-C-T			Uncertain significance (Apr 06, 2023)
4-147485924-C-T			Likely benign (May 22, 2018)
4-147485925-A-C			Uncertain significance (Apr 01, 2021)
4-147485930-C-A		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
4-147485937-A-G			Benign (Dec 26, 2023)
4-147485958-G-A			Uncertain significance (Aug 04, 2023)
4-147485967-G-A		Inborn genetic diseases	Uncertain significance (Dec 15, 2022)
4-147485984-G-C			Benign (Aug 16, 2022)
4-147485989-G-T			Uncertain significance (Nov 09, 2021)
4-147486029-C-T			Likely benign (Oct 02, 2022)
4-147486031-C-T			Uncertain significance (Sep 07, 2022)
4-147486035-G-A		Mandibulofacial dysostosis with alopecia;Migraine with or without aura, susceptibility to, 1	Likely benign (Apr 08, 2022)
4-147486067-A-G			Uncertain significance (Mar 13, 2023)
4-147486067-A-T		Mandibulofacial dysostosis with alopecia	Pathogenic (Apr 02, 2015)
4-147486078-G-A			Uncertain significance (Nov 10, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDNRA	protein_coding	protein_coding	ENST00000324300	7	64038

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00842	125742	0	4	125746	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.80	120	243	0.494	0.0000129	2864
Missense in Polyphen		31	107.35	0.28877		1272
Synonymous	0.617	80	87.3	0.916	0.00000507	786
Loss of Function	3.79	1	18.7	0.0534	9.46e-7	216

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
• Pathway: Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Renin secretion - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);GPCRs, Other;Endothelin Pathways;Peptide GPCRs;miR-509-3p alteration of YAP1-ECM axis;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;EGFR-dependent Endothelin signaling events;G alpha (q) signalling events;GPCR downstream signalling;Endothelins (Consensus)

Recessive Scores

• pRec: 0.415

Intolerance Scores

• loftool: 0.147
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.370
• hipred: Y
• hipred_score: 0.800
• ghis: 0.646

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.716

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ednra
• 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; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; hematopoietic system 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); 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); normal phenotype; digestive/alimentary 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; immune system phenotype

Zebrafish Information Network

• Gene name: ednrab
• Affected structure: pharyngeal arch 1
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: branching involved in blood vessel morphogenesis;response to hypoxia;in utero embryonic development;smooth muscle contraction;signal transduction;G protein-coupled receptor signaling pathway;activation of adenylate cyclase activity;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;activation of phospholipase C activity;positive regulation of cytosolic calcium ion concentration;heart development;respiratory gaseous exchange;regulation of blood pressure;cell population proliferation;regulation of glucose transmembrane transport;neural crest cell development;artery smooth muscle contraction;vasoconstriction;enteric nervous system development;head development;endothelin receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: phosphatidylinositol phospholipase C activity;endothelin receptor activity;protein binding