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

Summary

ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (MONDO:0013983) is a disease caused by EDARADD (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: EDARADD (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 48

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive
Mondo ID	MONDO:0013983
OMIM	614941
DOID	DOID:0111654
UMLS	C3539920
MedGen	761671
GARD	0015885
Is cancer (heuristic)	no

Also known as: ECTD11B · ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive

Data availability: 48 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive hypohidrotic ectodermal dysplasia › ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive

Related subtypes (1): ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

48 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 8 benign, 7 pathogenic, 5 likely pathogenic, 5 likely benign, 4 benign/likely benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
5853	NM_022336.4(EDAR):c.1259G>A (p.Arg420Gln)	EDAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2428490	NM_145861.4(EDARADD):c.469G>A (p.Glu157Lys)	EDARADD	Pathogenic	no assertion criteria provided
253093	NM_145861.4(EDARADD):c.120+1G>A	EDARADD	Pathogenic	no assertion criteria provided
280481	NM_145861.4(EDARADD):c.196C>T (p.Arg66Ter)	EDARADD	Pathogenic	criteria provided, multiple submitters, no conflicts
2939815	NC_000001.11:g.236468231_236468234del	EDARADD	Pathogenic	criteria provided, single submitter
473077	NM_145861.4(EDARADD):c.417G>A (p.Trp139Ter)	EDARADD	Pathogenic	criteria provided, single submitter
996824	NM_145861.4(EDARADD):c.85G>A (p.Glu29Lys)	EDARADD	Pathogenic	criteria provided, single submitter
996825	NM_145861.4(EDARADD):c.570C>A (p.Asp190Glu)	EDARADD	Pathogenic	criteria provided, single submitter
1347024	NC_000001.10:g.(?236631511)(236631596_?)dup	EDARADD	Likely pathogenic	criteria provided, single submitter
253092	NM_145861.4(EDARADD):c.367G>A (p.Asp123Asn)	EDARADD	Likely pathogenic	criteria provided, single submitter
3581597	NM_145861.4(EDARADD):c.61+1G>C	EDARADD	Likely pathogenic	criteria provided, single submitter
4188	NM_145861.4(EDARADD):c.454G>A (p.Glu152Lys)	EDARADD	Likely pathogenic	criteria provided, single submitter
4685519	NM_145861.4(EDARADD):c.548G>T (p.Cys183Phe)	EDARADD	Likely pathogenic	criteria provided, single submitter
843361	NM_145861.4(EDARADD):c.392C>T (p.Pro131Leu)	EDARADD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028539	NM_145861.4(EDARADD):c.440G>T (p.Gly147Val)	EDARADD	Uncertain significance	criteria provided, single submitter
1055040	NM_145861.4(EDARADD):c.568G>A (p.Asp190Asn)	EDARADD	Uncertain significance	criteria provided, single submitter
1354328	NM_145861.4(EDARADD):c.358_359delinsAT (p.Asp120Ile)	EDARADD	Uncertain significance	criteria provided, single submitter
1439044	NM_145861.4(EDARADD):c.446C>T (p.Ser149Phe)	EDARADD	Uncertain significance	criteria provided, single submitter
1514540	NC_000001.10:g.(?236631511)(236645949_?)dup	EDARADD	Uncertain significance	criteria provided, single submitter
1967978	NM_145861.4(EDARADD):c.22C>G (p.Gln8Glu)	EDARADD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2161136	NM_145861.4(EDARADD):c.101G>A (p.Ser34Asn)	EDARADD	Uncertain significance	criteria provided, single submitter
2188579	NM_145861.4(EDARADD):c.220G>A (p.Gly74Arg)	EDARADD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2938095	NM_145861.4(EDARADD):c.484A>G (p.Ser162Gly)	EDARADD	Uncertain significance	criteria provided, single submitter
2939545	NM_145861.4(EDARADD):c.154C>T (p.Pro52Ser)	EDARADD	Uncertain significance	criteria provided, single submitter
2945599	NM_145861.4(EDARADD):c.404C>T (p.Thr135Met)	EDARADD	Uncertain significance	criteria provided, single submitter
2952473	NM_145861.4(EDARADD):c.543G>T (p.Glu181Asp)	EDARADD	Uncertain significance	criteria provided, single submitter
2952474	NM_145861.4(EDARADD):c.548_549del (p.Leu182_Cys183insTer)	EDARADD	Uncertain significance	criteria provided, single submitter
3581599	NM_145861.4(EDARADD):c.358G>C (p.Asp120His)	EDARADD	Uncertain significance	criteria provided, multiple submitters, no conflicts
3759666	NM_145861.4(EDARADD):c.53A>G (p.His18Arg)	EDARADD	Uncertain significance	criteria provided, single submitter
540293	NM_145861.4(EDARADD):c.509G>A (p.Arg170Gln)	EDARADD	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
EDARADD	Strong	Autosomal dominant	ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EDARADD	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:99798	Oligodontia
EDAR	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDAR	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EDARADD	HGNC:14341	ENSG00000186197	Q8WWZ3	Ectodysplasin-A receptor-associated adapter protein	gencc,clinvar
EDAR	HGNC:2895	ENSG00000135960	Q9UNE0	Tumor necrosis factor receptor superfamily member EDAR	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EDARADD	Ectodysplasin-A receptor-associated adapter protein	Adapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs.
EDAR	Tumor necrosis factor receptor superfamily member EDAR	Receptor for EDA isoform A1, but not for EDA isoform A2.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EDARADD	Other/Unknown	no		Death_dom, DEATH-like_dom_sf, EDARADD
EDAR	Other/Unknown	no		DEATH-like_dom_sf, EDAR_N, TNR19/27/EDAR

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
oocyte	1
pancreatic ductal cell	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EDARADD	147	broad	marker	islet of Langerhans, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
EDAR	100	tissue_specific	yes	secondary oocyte, oocyte, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EDAR	1,307
EDARADD	659

Intra-cohort edges

A	B	Sources
EDAR	EDARADD	biogrid_interaction, intact, string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EDAR	Q9UNE0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EDARADD	Q8WWZ3	73.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TNFs bind their physiological receptors	2	393.8×	6e-06	EDARADD, EDAR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
salivary gland cavitation	1	1685.2×	0.008	EDAR
cell differentiation	2	29.1×	0.008	EDARADD, EDAR
pigmentation	1	351.1×	0.012	EDAR
hair follicle development	1	191.5×	0.017	EDAR
odontogenesis of dentin-containing tooth	1	150.5×	0.017	EDAR
positive regulation of non-canonical NF-kappaB signal transduction	1	127.7×	0.017	EDAR
epidermis development	1	105.3×	0.018	EDAR
positive regulation of JNK cascade	1	81.8×	0.020	EDAR
cytokine-mediated signaling pathway	1	65.3×	0.022	EDAR
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.036	EDAR
positive regulation of gene expression	1	19.4×	0.060	EDAR
apoptotic process	1	14.3×	0.074	EDAR
signal transduction	1	8.0×	0.121	EDARADD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EDARADD	0	0
EDAR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EDAR	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	EDARADD, EDAR

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EDARADD	0	—
EDAR	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.