EDARADD

EDAR associated via death domain

Basic information

Region (hg38): 1:236348257-236502915

Links

ENSG00000186197

∙ NCBI:128178 ∙ OMIM:606603 ∙ HGNC:14341 ∙ Uniprot:Q8WWZ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant (Moderate), mode of inheritance: Semidominant
autosomal recessive hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AR
autosomal dominant hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AD
tooth agenesis (Supportive), mode of inheritance: AD
ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant (Strong), mode of inheritance: AD
ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (Strong), mode of inheritance: AR
ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (Moderate), mode of inheritance: AR
ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant; Ectodermal dysplasia 11B, 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	Dental; Dermatologic	9245989; 11780064; 17354266; 20979233; 21626677; 21876339

ClinVar

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

Ectodermal_dysplasia_11B,_hypohidrotic/hair/tooth_type,_autosomal_recessive (36 variants)
Ectodermal_dysplasia_11A,_hypohidrotic/hair/tooth_type,_autosomal_dominant (34 variants)
Inborn_genetic_diseases (24 variants)
not_provided (18 variants)
Hypohidrotic_ectodermal_dysplasia (10 variants)
Hypohidrotic_Ectodermal_Dysplasia,_Recessive (6 variants)
not_specified (3 variants)
Ectodermal_dysplasia_10A,_hypohidrotic/hair/nail_type,_autosomal_dominant (3 variants)
ECTODERMAL_DYSPLASIA_11B,_HYPOHIDROTIC/HAIR/TOOTH_TYPE,_AUTOSOMAL_DOMINANT (1 variants)
Tooth_agenesis (1 variants)
EDARADD-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDARADD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000145861.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar	1 clinvar	8
missense	4 clinvar	7 clinvar	42 clinvar	1 clinvar		54
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	2 clinvar			4
Total	8	8	48	7	1

Highest pathogenic variant AF is 0.000015755346

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDARADD	protein_coding	protein_coding	ENST00000334232	6	136653

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000318	0.825	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	91	127	0.715	0.00000721	1445
Missense in Polyphen		34	59.14	0.57491		656
Synonymous	0.110	46	47.0	0.980	0.00000282	378
Loss of Function	1.21	7	11.4	0.614	5.78e-7	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000794	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000663	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Adapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs. Mediates the activation of NF- kappa-B. {ECO:0000269|PubMed:11882293}.;
Disease: DISEASE: Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (ECTD11B) [MIM:614941]: 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:11780064, ECO:0000269|PubMed:17354266, ECO:0000269|PubMed:20222921}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: 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: 0.0938

Intolerance Scores

loftool: 0.394
rvis_EVS: 0.19
rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

pHI: 0.123
hipred: N
hipred_score: 0.389
ghis: 0.451

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.637

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Edaradd
Phenotype: craniofacial phenotype; homeostasis/metabolism 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; endocrine/exocrine gland phenotype; pigmentation phenotype; limbs/digits/tail 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); hearing/vestibular/ear phenotype; vision/eye phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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); hematopoietic system phenotype;

Zebrafish Information Network

Gene name: edaradd
Affected structure: chondrocranium cartilage
Phenotype tag: abnormal
Phenotype quality: decreased size

Gene ontology

Biological process: multicellular organism development;cell differentiation;tumor necrosis factor-mediated signaling pathway
Cellular component: cytosol
Molecular function: protein binding