EDARADD

Chr 1ADAR

EDAR associated via death domain

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

NCBI Gene: 128178ENSG00000186197UniProt: Q8WWZ3

This gene was identified by its association with ectodermal dysplasia, a genetic disorder characterized by defective development of hair, teeth, and eccrine sweat glands. The protein encoded by this gene is a death domain-containing protein, and is found to interact with EDAR, a death domain receptor known to be required for the development of hair, teeth and other ectodermal derivatives. This protein and EDAR are coexpressed in epithelial cells during the formation of hair follicles and teeth. Through its interaction with EDAR, this protein acts as an adaptor, and links the receptor to downstream signaling pathways. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominantMIM #614940
AD
Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessiveMIM #614941
AR
245
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EDARADD
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 113 VUS of 245 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.14Z-score
OE missense 0.72 (0.60–0.85)
91 obs / 127.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.35–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.60–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 7 / 11.4Missense obs/exp: 91 / 127.3Syn Z: 0.11

ClinVar Variant Classifications

245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic11
VUS113
Likely Benign24
Benign41
Conflicting2
54
Pathogenic
11
Likely Pathogenic
113
VUS
24
Likely Benign
41
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
49
0
54
Likely Pathogenic
1
7
3
0
11
VUS
2
45
66
0
113
Likely Benign
0
1
15
8
24
Benign
0
1
39
1
41
Conflicting
—2
Total4581729245

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant

MIM #614940

Molecular basis of disorder known

Autosomal dominant

Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive

MIM #614941

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EDARADD
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
[Rickets-like genetic diseases].
Ma HW·Zhongguo Dang Dai Er Ke Za Zhi
2013Review
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
Novel homozygous frameshift insertion variant in the last exon of the EDARADD causing hypohidrotic ectodermal dysplasia in two siblings: case report and review of the literature.
Kablan A et al.·Ital J Pediatr
2024Review
EDARADD silencing suppresses the proliferation and migration of bladder cancer cells.
Fang Z et al.·Urol Oncol
2022
EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population.
Martínez-Romero MC et al.·Orphanet J Rare Dis
2019Cohort
Dissecting the Genetic Contribution of Tooth Agenesis.
Fallea A et al.·Int J Mol Sci
2025Review
Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases.
Cluzeau C et al.·Hum Mutat
2011Cohort
A novel EDAR variant identified in non-syndromic tooth agenesis: Insights from molecular dynamics.
Zhao Z et al.·Arch Oral Biol
2023
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
Hypohidrotic Ectodermal Dysplasias: Phenotypic and Genotypic Findings in 32 Cases.
Esener Z et al.·Clin Genet
2026Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools