EDARADD

EDAR associated via death domain

Basic information

Region (hg38): 1:236348257-236502915

Links

ENSG00000186197NCBI:128178OMIM:606603HGNC:14341Uniprot:Q8WWZ3AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant; Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessiveAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDental; Dermatologic9245989; 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 (3 variants)
  • Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive;Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant (1 variants)
  • not provided (1 variants)
  • Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (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.

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
7
clinvar
7
missense
2
clinvar
4
clinvar
30
clinvar
1
clinvar
1
clinvar
38
nonsense
2
clinvar
1
clinvar
3
start loss
0
frameshift
1
clinvar
2
clinvar
3
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
1
1
3
5
non coding
41
clinvar
12
clinvar
31
clinvar
84
Total 5 4 75 20 32

Highest pathogenic variant AF is 0.00000657

Variants in EDARADD

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

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

Position Type Phenotype Significance ClinVar
1-236394112-T-G Benign (Nov 11, 2018)1226215
1-236394442-G-A not specified • Hypohidrotic Ectodermal Dysplasia, Recessive • Hypohidrotic ectodermal dysplasia Benign/Likely benign (Jan 13, 2018)262598
1-236394459-G-A Likely benign (Oct 16, 2017)722615
1-236394466-C-G Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Uncertain significance (Aug 08, 2022)1967978
1-236394471-G-A not specified • Hypohidrotic Ectodermal Dysplasia, Recessive • Hypohidrotic ectodermal dysplasia • Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive • Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant • Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Benign (Jan 31, 2024)262600
1-236394504-G-A not specified • Hypohidrotic Ectodermal Dysplasia, Recessive • Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive • Hypohidrotic ectodermal dysplasia Benign/Likely benign (Jan 29, 2024)282055
1-236394623-G-T Benign (May 12, 2021)1277162
1-236394628-G-A not specified Benign (Nov 11, 2018)439637
1-236395596-C-T Likely benign (Jun 05, 2019)1223643
1-236395749-G-A Benign (May 25, 2021)1295013
1-236408953-T-G Benign (Jun 18, 2021)1240648
1-236409068-T-TA Benign (May 21, 2021)1255321
1-236409089-G-A Benign (Nov 11, 2018)1295882
1-236409175-A-G Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant • Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Benign (Jul 30, 2021)1255368
1-236409198-T-C Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Likely benign (Aug 17, 2023)2929835
1-236409234-C-T Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant Uncertain significance (Mar 29, 2024)3065706
1-236409239-G-A Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Pathogenic (Feb 13, 2021)996824
1-236409255-G-A Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Uncertain significance (Aug 08, 2022)2161136
1-236409258-C-A Inborn genetic diseases Uncertain significance (Jan 02, 2024)3087124
1-236409269-A-G Hypohidrotic Ectodermal Dysplasia, Recessive • Hypohidrotic ectodermal dysplasia • Inborn genetic diseases Conflicting classifications of pathogenicity (Jan 18, 2022)296448
1-236409275-G-A Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Pathogenic (Aug 09, 2016)253093
1-236409281-G-A Hypohidrotic ectodermal dysplasia • Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant;Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive Benign (Jul 04, 2022)876048
1-236409284-A-G Likely benign (Jul 31, 2018)779586
1-236409544-T-G Benign (Jun 18, 2021)1295851
1-236414050-T-C Benign (May 12, 2021)1287437

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EDARADDprotein_codingprotein_codingENST00000334232 6136653
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0003180.8251257300181257480.0000716
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.14911270.7150.000007211445
Missense in Polyphen3459.140.57491656
Synonymous0.1104647.00.9800.00000282378
Loss of Function1.21711.40.6145.78e-7132

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001480.000148
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.00007940.0000791
Middle Eastern0.0001090.000109
South Asian0.00006630.0000653
Other0.0001630.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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