EDAR

ectodysplasin A receptor, the group of Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 2:108894471-108989372

Previous symbols: [ "ED3", "DL" ]

Links

ENSG00000135960 ∙ NCBI:10913 ∙ OMIM:604095 ∙ HGNC:2895 ∙ Uniprot:Q9UNE0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (Definitive), mode of inheritance: AR
• autosomal recessive hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AR
• autosomal dominant hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AD
• ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (Strong), mode of inheritance: AD
• ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive	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; Hair morphology 1 is of unclear clinical significance	Dental; Dermatologic	10431241; 15373768; 16029325; 18816645; 18231121; 20979233; 21771270; 21876339; 22032522

ClinVar

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

• Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant;Autosomal recessive hypohidrotic ectodermal dysplasia syndrome (26 variants)
• not provided (8 variants)
• Autosomal recessive hypohidrotic ectodermal dysplasia syndrome;Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (6 variants)
• Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (3 variants)
• Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (3 variants)
• Ectodermal dysplasia 10a, hypohidrotic/hair/tooth type, autosomal dominant (2 variants)
• Mitochondrial DNA depletion syndrome 4b;Progressive sclerosing poliodystrophy (2 variants)
• Non-syndromic oligodontia (1 variants)
• Inborn genetic diseases (1 variants)
• Ectodermal dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDAR 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			4	28	9	41
missense	15	13	69	2	4	103
nonsense	8	2	1			11
start loss						0
frameshift	12	3				15
inframe indel			3			3
splice donor/acceptor (+/-2bp)	5	2	1			8
splice region			2	2		4
non coding			43	17	39	99
Total	40	20	121	47	52

Highest pathogenic variant AF is 0.0000197

Variants in EDAR

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

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

Position	Type	Phenotype	Significance	ClinVar
2-108894476-TTAATG-T		Hypohidrotic Ectodermal Dysplasia, Dominant	Uncertain significance (Jun 14, 2016)
2-108894481-G-A		Hypohidrotic Ectodermal Dysplasia, Dominant • Hypohidrotic ectodermal dysplasia	Benign (Jan 12, 2018)
2-108894531-A-G		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 12, 2018)
2-108894718-C-A		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108894752-A-ATAAG		Hypohidrotic Ectodermal Dysplasia, Dominant	Likely benign (Jun 14, 2016)
2-108894766-A-G		Hypohidrotic ectodermal dysplasia	Benign (Jan 12, 2018)
2-108894829-A-G		Hypohidrotic ectodermal dysplasia	Benign (Jan 13, 2018)
2-108894891-C-G		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895007-G-A		Hypohidrotic Ectodermal Dysplasia, Dominant • Hypohidrotic ectodermal dysplasia	Benign/Likely benign (Jan 13, 2018)
2-108895011-GACTC-G		Hypohidrotic Ectodermal Dysplasia, Dominant	Likely benign (Jun 14, 2016)
2-108895109-C-G		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895133-C-T		Hypohidrotic ectodermal dysplasia	Benign (Jan 12, 2018)
2-108895146-C-T		Hypohidrotic Ectodermal Dysplasia, Dominant • Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895197-C-G		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895204-C-T		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895229-G-A		Hypohidrotic ectodermal dysplasia	Benign (Jan 13, 2018)
2-108895260-G-A		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895309-A-G		Hypohidrotic Ectodermal Dysplasia, Dominant • Hypohidrotic ectodermal dysplasia	Benign (Jan 12, 2018)
2-108895344-G-A		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895372-G-A		Hypohidrotic Ectodermal Dysplasia, Dominant • Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895472-C-T		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)
2-108895541-T-C		Hypohidrotic ectodermal dysplasia	Likely benign (Jan 13, 2018)
2-108895543-A-C		Hypohidrotic ectodermal dysplasia	Likely benign (Jan 13, 2018)
2-108895588-G-C		Hypohidrotic Ectodermal Dysplasia, Dominant • Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 12, 2018)
2-108895609-C-G		Hypohidrotic ectodermal dysplasia	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDAR	protein_coding	protein_coding	ENST00000258443	11	94902

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000132	0.955	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.728	245	279	0.877	0.0000175	2914
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000348	0.000333
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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;Immune System;TNFs bind their physiological receptors (Consensus)

Recessive Scores

• pRec: 0.447

Intolerance Scores

• loftool: 0.158
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.46

Haploinsufficiency Scores

• pHI: 0.193
• hipred: Y
• hipred_score: 0.569
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.884

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Edar
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland 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); growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; pigmentation 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); reproductive 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); skeleton phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: edar
• Affected structure: pectoral fin distal radial
• Phenotype tag: abnormal
• Phenotype quality: fused with

Gene ontology

• Biological process: hair follicle development;apoptotic process;epidermis development;positive regulation of gene expression;cell differentiation;tumor necrosis factor-mediated signaling pathway;odontogenesis of dentin-containing tooth;positive regulation of I-kappaB kinase/NF-kappaB signaling;pigmentation;positive regulation of JNK cascade;salivary gland cavitation;positive regulation of NIK/NF-kappaB signaling
• Cellular component: plasma membrane;integral component of membrane;apical part of cell
• Molecular function: transmembrane signaling receptor activity;protein binding;signaling receptor activity