EDARADD

Chr 1ADAR

EDAR associated via death domain

Also known as: CR, ECTD11A, ECTD11B, ED3, EDA3

NCBI Gene: 128178ENSG00000186197UniProt: Q8WWZ3OMIM: 606603

The protein functions as an adapter that couples the EDAR receptor to downstream NF-kappa-B signaling pathways during morphogenesis of ectodermal organs including hair follicles, teeth, and sweat glands. Mutations cause ectodermal dysplasia affecting hair, teeth, and sweat gland development, with both autosomal dominant and autosomal recessive inheritance patterns described. The gene shows low constraint against loss-of-function variants (pLI 0.0003, LOEUF 1.15), consistent with recessive disease mechanisms being possible.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 1.152 OMIM phenotypes
Clinical Summary— EDARADD
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 43 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 1.21
OE 0.61 (0.35–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.14Z-score
OE missense 0.72 (0.60–0.85)
91 obs / 127.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.35–1.15)
0≤0.351.4
Missense OE0.72 (0.60–0.85)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 7 / 11.4Missense obs/exp: 91 / 127.3Syn Z: 0.11
DN
0.6064th %ile
GOF
0.7125th %ile
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DN1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNNuclear factor (NF)-kB reporter assays demonstrated that all the mutant EDARADD showed reduction in activation of NF-?B. Importantly, p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD slightly reduced the NF-kB activity induced by wild-type EDARADD in a dominant negative manner.PMID:34219261

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic3
VUS43
Likely Benign10
Benign22
Conflicting1
21
Pathogenic
3
Likely Pathogenic
43
VUS
10
Likely Benign
22
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
18
0
21
Likely Pathogenic
0
2
1
0
3
VUS
1
5
37
0
43
Likely Benign
0
0
7
3
10
Benign
0
0
21
1
22
Conflicting
—1
Total29844100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EDARADD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 2 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Novel insight into the ectodermal dysplasia 11A: Splicing variant of the EDARADD gene in a family with clinical variability and literature review.
Fazelzadeh Haghighi N et al.·J Dermatol
2023Review
EDARADD silencing suppresses the proliferation and migration of bladder cancer cells.
Fang Z et al.·Urol Oncol
2022
Gene Mutations of the Three Ectodysplasin Pathway Key Players (EDA, EDAR, and EDARADD) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations.
Ahmed HA et al.·Genes (Basel)
2021
Characterization of EDARADD gene mutations responsible for hypohidrotic ectodermal dysplasia.
Asano N et al.·J Dermatol
2021
EDARADD promotes colon cancer progression by suppressing E3 ligase Trim21-mediated ubiquitination and degradation of Snail.
Yang J et al.·Cancer Lett
2023
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients