ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant

Summary

ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (MONDO:0007509) is a disease caused by EDAR (GenCC Strong), with 4 cohort genes.

At a glance

• Causal gene: EDAR (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 195

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant
Mondo ID	MONDO:0007509
OMIM	129490
DOID	DOID:0111663
UMLS	C3888065
MedGen	854747
GARD	0018591
Is cancer (heuristic)	no

Also known as: ECTD10A · ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant · ectodermal dysplasia hypohidrotic autosomal dominant · hypohidrotic ectodermal dysplasia autosomal dominant

Data availability: 195 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 dominant disease › autosomal dominant hypohidrotic ectodermal dysplasia › ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant

Related subtypes (1): ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant

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

195 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 37 pathogenic, 24 likely benign, 18 likely pathogenic, 18 benign, 16 conflicting classifications of pathogenicity, 7 benign/likely benign, 7 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075576	NM_022336.4(EDAR):c.964-1G>A	EDAR	Pathogenic	criteria provided, single submitter
1452944	NM_022336.4(EDAR):c.1097_1098del (p.Asn365_Ser366insTer)	EDAR	Pathogenic	criteria provided, single submitter
1714868	NM_022336.4(EDAR):c.1282T>C (p.Cys428Arg)	EDAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1721247	NM_022336.4(EDAR):c.1292T>C (p.Ile431Thr)	EDAR	Pathogenic	criteria provided, single submitter
194115	NM_022336.4(EDAR):c.1144G>A (p.Gly382Ser)	EDAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2052298	NM_022336.4(EDAR):c.1297G>T (p.Glu433Ter)	EDAR	Pathogenic	criteria provided, single submitter
2075534	NM_022336.4(EDAR):c.293G>A (p.Arg98Gln)	EDAR	Pathogenic	criteria provided, single submitter
265471	NM_022336.4(EDAR):c.1073G>A (p.Arg358Gln)	EDAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2944544	NM_022336.4(EDAR):c.1221del (p.Ser407fs)	EDAR	Pathogenic	criteria provided, single submitter
2946816	NM_022336.4(EDAR):c.641dup (p.Pro215fs)	EDAR	Pathogenic	criteria provided, single submitter
2948715	NM_022336.4(EDAR):c.1024+2T>C	EDAR	Pathogenic	criteria provided, single submitter
2950142	NM_022336.4(EDAR):c.1280T>C (p.Leu427Ser)	EDAR	Pathogenic	criteria provided, single submitter
2952436	NM_022336.4(EDAR):c.931del (p.Glu311fs)	EDAR	Pathogenic	criteria provided, single submitter
2952572	NM_022336.4(EDAR):c.1218C>G (p.Tyr406Ter)	EDAR	Pathogenic	criteria provided, single submitter
3247228	NC_000002.11:g.(?109513363)(109524495_?)del	EDAR	Pathogenic	criteria provided, single submitter
3756461	NM_022336.4(EDAR):c.1024+1G>T	EDAR	Pathogenic	criteria provided, single submitter
3759646	NM_022336.4(EDAR):c.1090del (p.Tyr364fs)	EDAR	Pathogenic	criteria provided, single submitter
417939	NM_022336.4(EDAR):c.284del (p.Gly95fs)	EDAR	Pathogenic	no assertion criteria provided
449014	NM_022336.4(EDAR):c.903C>A (p.Cys301Ter)	EDAR	Pathogenic	criteria provided, multiple submitters, no conflicts
463874	NM_022336.4(EDAR):c.1024+1G>A	EDAR	Pathogenic	criteria provided, single submitter
463876	NM_022336.4(EDAR):c.1132G>A (p.Ala378Thr)	EDAR	Pathogenic	criteria provided, single submitter
4786258	NM_022336.4(EDAR):c.983del (p.Lys328fs)	EDAR	Pathogenic	criteria provided, single submitter
4789004	NM_022336.4(EDAR):c.757del (p.Asp253fs)	EDAR	Pathogenic	criteria provided, single submitter
532547	NM_022336.4(EDAR):c.1193_1194del (p.Leu397_Phe398insTer)	EDAR	Pathogenic	criteria provided, single submitter
532549	NM_022336.4(EDAR):c.292C>T (p.Arg98Trp)	EDAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
562015	NM_022336.4(EDAR):c.265C>T (p.Arg89Cys)	EDAR	Pathogenic	criteria provided, single submitter
566967	NM_022336.4(EDAR):c.1089del (p.Tyr364fs)	EDAR	Pathogenic	criteria provided, single submitter
569147	NM_022336.4(EDAR):c.931G>T (p.Glu311Ter)	EDAR	Pathogenic	criteria provided, single submitter
579211	NM_022336.4(EDAR):c.1169dup (p.Met391fs)	EDAR	Pathogenic	criteria provided, single submitter
5849	NM_022336.4(EDAR):c.266G>A (p.Arg89His)	EDAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 8 · 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
EDAR	Definitive	Autosomal recessive	ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EDAR	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDAR	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:99798	Oligodontia
RANBP2	Orphanet:178342	Inflammatory myofibroblastic tumor
RANBP2	Orphanet:263524	Acute necrotizing encephalopathy of childhood
RANBP2	Orphanet:88619	Familial acute necrotizing encephalopathy

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EDAR	HGNC:2895	ENSG00000135960	Q9UNE0	Tumor necrosis factor receptor superfamily member EDAR	gencc,clinvar
EDARADD	HGNC:14341	ENSG00000186197	Q8WWZ3	Ectodysplasin-A receptor-associated adapter protein	clinvar
CCDC138	HGNC:26531	ENSG00000163006	Q96M89	Coiled-coil domain-containing protein 138	clinvar
RANBP2	HGNC:9848	ENSG00000153201	P49792	E3 SUMO-protein ligase RanBP2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EDAR	Tumor necrosis factor receptor superfamily member EDAR	Receptor for EDA isoform A1, but not for EDA isoform A2.
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.
RANBP2	E3 SUMO-protein ligase RanBP2	E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · 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
Transcription factor	1	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EDAR	Other/Unknown	no		DEATH-like_dom_sf, EDAR_N, TNR19/27/EDAR
EDARADD	Other/Unknown	no		Death_dom, DEATH-like_dom_sf, EDARADD
CCDC138	Other/Unknown	no		CCDC138, CCDC138_C, CCDC138_CC
RANBP2	Transcription factor	no		Ran_bind_dom, Znf_RanBP2, Cyclophilin-type_PPIase_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
sperm	2
oocyte	1
pancreatic ductal cell	1
secondary oocyte	1
islet of Langerhans	1
sural nerve	1
ventricular zone	1
endothelial cell	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EDAR	100	tissue_specific	yes	secondary oocyte, oocyte, pancreatic ductal cell
EDARADD	147	broad	marker	islet of Langerhans, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
CCDC138	178	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, sperm, ventricular zone
RANBP2	294	ubiquitous	marker	endothelial cell, sperm, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RANBP2	7,348
EDAR	1,307
CCDC138	829
EDARADD	659

Intra-cohort edges

A	B	Sources
EDAR	EDARADD	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RANBP2	P49792	33
EDAR	Q9UNE0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EDARADD	Q8WWZ3	73.81
CCDC138	Q96M89	73.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 4 evidence-associated genes (3 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 3 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	262.5×	7e-04	EDAR, EDARADD
IPs transport between nucleus and cytosol	1	126.9×	0.023	RANBP2
IP3 and IP4 transport between cytosol and nucleus	1	126.9×	0.023	RANBP2
IP6 and IP7 transport between cytosol and nucleus	1	126.9×	0.023	RANBP2
Transport of Ribonucleoproteins into the Host Nucleus	1	119.0×	0.023	RANBP2
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	119.0×	0.023	RANBP2
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	119.0×	0.023	RANBP2
NEP/NS2 Interacts with the Cellular Export Machinery	1	115.3×	0.023	RANBP2
Nuclear import of Rev protein	1	112.0×	0.023	RANBP2
Vpr-mediated nuclear import of PICs	1	112.0×	0.023	RANBP2
Transport of the SLBP independent Mature mRNA	1	108.8×	0.023	RANBP2
SUMOylation of SUMOylation proteins	1	108.8×	0.023	RANBP2
Transport of the SLBP Dependant Mature mRNA	1	105.7×	0.023	RANBP2
Rev-mediated nuclear export of HIV RNA	1	105.7×	0.023	RANBP2
Nuclear Pore Complex (NPC) Disassembly	1	102.9×	0.023	RANBP2
SUMOylation of ubiquitinylation proteins	1	97.6×	0.023	RANBP2
NS1 Mediated Effects on Host Pathways	1	95.2×	0.023	RANBP2
Transport of Mature mRNA Derived from an Intronless Transcript	1	90.6×	0.023	RANBP2
Viral Messenger RNA Synthesis	1	86.5×	0.023	RANBP2
SUMOylation of DNA replication proteins	1	82.8×	0.023	RANBP2
SUMOylation of RNA binding proteins	1	79.3×	0.023	RANBP2
snRNP Assembly	1	70.5×	0.024	RANBP2
tRNA processing in the nucleus	1	65.6×	0.025	RANBP2
SUMOylation of chromatin organization proteins	1	52.9×	0.028	RANBP2
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	50.8×	0.028	RANBP2
ISG15 antiviral mechanism	1	50.1×	0.028	RANBP2
Signaling by ALK fusions and activated point mutants	1	50.1×	0.028	RANBP2
SUMOylation of DNA damage response and repair proteins	1	48.8×	0.028	RANBP2
Regulation of HSF1-mediated heat shock response	1	46.4×	0.028	RANBP2
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	38.8×	0.032	RANBP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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	1123.5×	0.015	EDAR
nuclear export	1	510.7×	0.015	RANBP2
regulation of gluconeogenesis	1	374.5×	0.015	RANBP2
centrosome localization	1	295.6×	0.015	RANBP2
NLS-bearing protein import into nucleus	1	267.5×	0.015	RANBP2
pigmentation	1	234.1×	0.015	EDAR
cell differentiation	2	19.4×	0.015	EDAR, EDARADD
intracellular glucose homeostasis	1	193.7×	0.015	RANBP2
response to amphetamine	1	165.2×	0.016	RANBP2
nucleocytoplasmic transport	1	130.6×	0.017	RANBP2
hair follicle development	1	127.7×	0.017	EDAR
protein sumoylation	1	108.0×	0.018	RANBP2
odontogenesis of dentin-containing tooth	1	100.3×	0.018	EDAR
mRNA transport	1	87.8×	0.019	RANBP2
positive regulation of non-canonical NF-kappaB signal transduction	1	85.1×	0.019	EDAR
epidermis development	1	70.2×	0.021	EDAR
positive regulation of JNK cascade	1	54.5×	0.026	EDAR
cytokine-mediated signaling pathway	1	43.5×	0.030	EDAR
protein folding	1	34.5×	0.036	RANBP2
positive regulation of canonical NF-kappaB signal transduction	1	24.2×	0.049	EDAR
positive regulation of gene expression	1	12.9×	0.086	EDAR
apoptotic process	1	9.6×	0.110	EDAR
negative regulation of transcription by RNA polymerase II	1	5.9×	0.167	RANBP2
signal transduction	1	5.3×	0.176	EDARADD

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 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
EDAR	0	0
EDARADD	0	0
CCDC138	0	0
RANBP2	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
RANBP2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	EDAR, EDARADD, CCDC138, RANBP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EDAR	1	—
EDARADD	0	—
CCDC138	0	—
RANBP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.