EDAR
protein-codingectodysplasin A receptor, the group of Tumor necrosis factor receptor superfamily
Gene summary
This gene encodes a member of the tumor necrosis factor receptor family. The encoded transmembrane protein is a receptor for the soluble ligand ectodysplasin A, and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives. Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]
- ED3
- DL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~94.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009147
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007509
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009147
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0015884
Submitter: Orphanet
Inheritance Pattern: SD
Disease ID:MONDO:0016535
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0009147
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0016619
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009147
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009147
Submitter: ClinGen
*EDAR* was first reported in relation to autosomal recessive hypohidrotic ectodermal dysplasia in 1999 (Monreal et al., PMID: 10431241). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in inheritance pattern and molecular mechanism. Therefore, the following disease entities have been split into multiple disease entities, autosomal dominant hypohidrotic ectodermal dysplasia (OMIM:129490), autosomal recessive hypohidrotic ectodermal dysplasia (OMIM:224900), and nonsyndromic tooth agenesis. The split curations for autosomal dominant hypohidrotic ectodermal dysplasia and nonsyndromic tooth agenesis will be curated separately. 19 variants (missense, splice site, frameshift, small deletion) that have been reported in 15 probands in seven publications (PMIDs: 10431241, 16435307, 18816645, 16029325, 15373768, 17501952, 20979233) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is loss-of-function. This gene-disease relationship is also supported by a mouse model of reduced cusp number and tooth size in mice with loss-of-function variants in EDAR (PMID:19340299). An expression study showed that EDAR was expressed in the outer and inner root sheaths and secondary hair germ, and EDAR signaling was shown to be involved in hair cycle control (PMID:17148670). Additionally, the expression pattern of EDAR-null mice during tooth morphogenesis was restricted to ectodermal tissue (PMID:11203701). In summary, there is definitive evidence supporting the relationship between *EDAR* and autosomal recessive hypohidrotic ectodermal dysplasia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations GCEP on the meeting date July 16, 2026 (SOP Version 12).
Inheritance Pattern: AD
Disease ID:MONDO:0007509
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dental; Dermatologic
Intervention: General
Rationale: 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; Hair morphology 1 is of unclear clinical significance
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EDAR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022336.4. 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 | 4 | 40 | 5 | 49 | ||
| missense | 15 | 34 | 117 | 13 | 2 | 181 |
| nonsense | 8 | 7 | 15 | |||
| start loss | 0 | |||||
| frameshift | 20 | 9 | 29 | |||
| splice donor/acceptor (+/-2bp) | 9 | 5 | 14 | |||
| Total | 52 | 55 | 121 | 53 | 7 | 288 |
Highest pathogenic variant AF is 0.00007994814
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071731.1 | 11 | MANE Select | |
| Ensembl | ENSP00000258443.2 | 11 | MANE Select | |
| Ensembl | ENSP00000365839.1 | 10 | Standard | |
| Ensembl | ENSP00000365839.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| edar | Danio rerio | Structure: pectoral fin distal radial Quality: fused with abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- Hair Follicle Development- Induction (Part 1 of 3)
- EDA Signalling in Hair Follicle Development
- TNFR2 non-canonical NF-kB pathway
- Cytokine Signaling in Immune system
Biological Process
- hair follicle development
- apoptotic process
- epidermis development
- positive regulation of gene expression
- cell differentiation
Molecular Function
- transmembrane signaling receptor activity
- protein binding
- signaling receptor activity
Cellular Component
- plasma membrane
- integral component of membrane
- apical part of cell
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258443
- Coding exons
- 11
- Length
- 94902
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 37
- Defined
- 125748
- p
- 0.000147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.728 | 245 | 279 | 0.877 | 0.0000175 | 2914 |
| Missense (PolyPhen) | 121 | 146.59 | 0.82541 | 1517 | ||
| Synonymous | -0.237 | 126 | 123 | 1.03 | 0.00000916 | 876 |
| Loss of Function | 1.90 | 13 | 22.8 | 0.570 | 0.00000115 | 267 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00025 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00021 | 0.00021 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.;
- Disease
- DISEASE: Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (ECTD10A) [MIM:129490]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands. {ECO:0000269|PubMed:10431241, ECO:0000269|PubMed:18231121}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (ECTD10B) [MIM:224900]: A disorder due to abnormal development of two or more ectodermal structures, and characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. {ECO:0000269|PubMed:10431241, ECO:0000269|PubMed:15373768, ECO:0000269|PubMed:16029325, ECO:0000269|PubMed:16435307, ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:19438931, ECO:0000269|PubMed:20979233, ECO:0000269|PubMed:27657131}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.447
Intolerance Scores
- LoFtool
- 0.158
- RVIS EVS
- -0.44
- RVIS percentile EVS
- 24.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.884
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |