EDNRA
protein-codingendothelin receptor type A, the group of Endothelin receptors
Gene summary
This gene encodes the receptor for endothelin-1, a peptide that plays a role in potent and long-lasting vasoconstriction. This receptor associates with guanine-nucleotide-binding (G) proteins, and this coupling activates a phosphatidylinositol-calcium second messenger system. Polymorphisms in this gene have been linked to migraine headache resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~64.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009061
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014608
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014608
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014608
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0014608
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014608
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Ophthalmologic
Intervention: Audiologic/Otolaryngologic
Rationale: Among other features, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EDNRA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001957.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 27 | 28 | |||
| missense | 2 | 1 | 76 | 2 | 2 | 83 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 1 | 77 | 29 | 2 | 111 |
Highest pathogenic variant AF is 6.840759e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001948.1 | 7 | MANE Select | |
| Ensembl | ENSP00000498969.1 | 7 | MANE Select | |
| RefSeq | NP_001159527.1 | 5 | Standard | |
| RefSeq | NP_001341726.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ednrab | Danio rerio | Structure: pharyngeal arch 1 Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- branching involved in blood vessel morphogenesis
- response to hypoxia
- in utero embryonic development
- smooth muscle contraction
- signal transduction
Molecular Function
- phosphatidylinositol phospholipase C activity
- endothelin receptor activity
- protein binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324300
- Coding exons
- 7
- Length
- 64038
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125746
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.80 | 120 | 243 | 0.494 | 0.0000129 | 2864 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000065 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.415
Intolerance Scores
- LoFtool
- 0.147
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.716
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |