Hypohidrotic ectodermal dysplasia

Summary

Hypohidrotic ectodermal dysplasia (MONDO:0016535) is a disease caused by variants in EDAR and EDARADD, with 4 cohort genes and 9 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal genes: EDAR (GenCC Strong), EDARADD (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 162
• Phenotypes (HPO): 31
• Clinical trials: 9

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	6.7	Europe	Validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000327	Hypoplasia of the maxilla	Very frequent (80-99%)
HP:0000958	Dry skin	Very frequent (80-99%)
HP:0000963	Thin skin	Very frequent (80-99%)
HP:0001097	Keratoconjunctivitis sicca	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0006482	Abnormal dental morphology	Very frequent (80-99%)
HP:0007400	Irregular hyperpigmentation	Very frequent (80-99%)
HP:0009804	Tooth agenesis	Very frequent (80-99%)
HP:0010978	Abnormality of immune system physiology	Very frequent (80-99%)
HP:0012471	Thick vermilion border	Very frequent (80-99%)
HP:0000100	Nephrotic syndrome	Frequent (30-79%)
HP:0000217	Xerostomia	Frequent (30-79%)
HP:0000246	Sinusitis	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000962	Hyperkeratosis	Frequent (30-79%)
HP:0000964	Eczematoid dermatitis	Frequent (30-79%)
HP:0000966	Hypohidrosis	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002217	Slow-growing hair	Frequent (30-79%)
HP:0004298	Abnormality of the abdominal wall	Frequent (30-79%)
HP:0009886	Trichorrhexis nodosa	Frequent (30-79%)
HP:0011358	Generalized hypopigmentation of hair	Frequent (30-79%)
HP:0012735	Cough	Frequent (30-79%)
HP:0100533	Inflammatory abnormality of the eye	Frequent (30-79%)
HP:0100840	Aplasia/Hypoplasia of the eyebrow	Frequent (30-79%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001597	Abnormality of the nail	Occasional (5-29%)
HP:0011362	Abnormal hair quantity	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)
HP:0100783	Breast aplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hypohidrotic ectodermal dysplasia
Mondo ID	MONDO:0016535
Orphanet	238468
DOID	DOID:14793
ICD-11	673167184
NCIT	C84562
UMLS	C5848103
MedGen	1853123
GARD	0000076
NORD	1272
Is cancer (heuristic)	no

Also known as: anhidrotic ectodermal dysplasia · anhidrotic ectodermal dysplasia 1 · anhidrotic ectodermal dysplasia 3 · CST syndrome · ectodermal dysplasia 1, Anhydrotic · ectodermal dysplasia anhidrotic · ectodermal dysplasia, hypohidrotic · EDA · HED · hypohidrotic X-linked ectodermal dysplasia

Data availability: 162 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype · 3 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › hypohidrotic ectodermal dysplasia

Related subtypes (119): ADULT syndrome, autosomal dominant palmoplantar keratoderma and congenital alopecia, ameloonychohypohidrotic syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, anonychia with flexural pigmentation, Böök syndrome, blepharocheilodontic syndrome, Stern-Lubinsky-Durrie syndrome, dermatopathia pigmentosa reticularis, dermo-odonto dysplasia, Rapp-Hodgkin syndrome, Clouston syndrome, ectodermal dysplasia, trichoodontoonychial type, gingival fibromatosis-hypertrichosis syndrome, hypertrichosis cubiti-short stature syndrome, Johnson neuroectodermal syndrome, Marshall syndrome, Naegeli-Franceschetti-Jadassohn syndrome, oculodentodigital dysplasia, Cronkhite-Canada syndrome, scalp-ear-nipple syndrome, tooth and nail syndrome, tricho-dento-osseous syndrome, tricho-retino-dento-digital syndrome, acrofacial dysostosis, Weyers type, Ackerman syndrome, alopecia - contractures - dwarfism - intellectual disability syndrome, AREDYLD syndrome, Barber-Say syndrome, oculoosteocutaneous syndrome, cataract-hypertrichosis-intellectual disability syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, cerebellar ataxia-ectodermal dysplasia syndrome, cranioectodermal dysplasia, conductive deafness-ptosis-skeletal anomalies syndrome, dermatoosteolysis, Kirghizian type, Dubowitz syndrome, ectodermal dysplasia-sensorineural deafness syndrome, ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome, hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome, cleft lip/palate-ectodermal dysplasia syndrome, EEM syndrome, Ellis-van Creveld syndrome, amelocerebrohypohidrotic syndrome, GAPO syndrome, ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome, Leukomelanoderma-infantilism-intellectual disability-hypodontia-hypotrichosis syndrome, Dahlberg-Borer-Newcomer syndrome, cartilage-hair hypoplasia, oculotrichodysplasia, pilodental dysplasia-refractive errors syndrome, Bartsocas-Papas syndrome 1, ectodermal dysplasia-blindness syndrome, Schinzel-Giedion syndrome, Teebi-Shaltout syndrome, taurodontia-absent teeth-sparse hair syndrome, odontotrichomelic syndrome, trichomegaly-retina pigmentary degeneration-dwarfism syndrome, trichoodontoonychial dysplasia, CHIME syndrome, anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome, Ito hypomelanosis, contractures-ectodermal dysplasia-cleft lip/palate syndrome, incontinentia pigmenti, Toriello-Lacassie-Droste syndrome, odontomicronychial dysplasia, ectodermal dysplasia with natal teeth, Turnpenny type, hidrotic ectodermal dysplasia, Christianson-Fourie type, trichodental syndrome, congenital hypotrichosis with juvenile macular dystrophy, tricho-oculo-dermo-vertebral syndrome, odonto-tricho-ungual-digito-palmar syndrome, Fried’s tooth and nail syndrome, limb-mammary syndrome, epidermolysis bullosa simplex due to plakophilin deficiency, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, Curly hair - acral keratoderma - caries syndrome, hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma syndrome, Lelis syndrome, Fontaine progeroid syndrome, ectodermal dysplasia-syndactyly syndrome, ectodermal dysplasia 5, hair/nail type, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, cardiofaciocutaneous syndrome, choroidal atrophy-alopecia syndrome, dyskeratosis congenita, hidrotic ectodermal dysplasia, Halal type, hypertrichosis lanuginosa congenita, odonto-onycho dysplasia-alopecia syndrome, pili torti-onychodysplasia syndrome, chondroectodermal dysplasia with night blindness, trichorhinophalangeal syndrome, trichothiodystrophy, trichodermodysplasia-dental alterations syndrome, autosomal dominant trichoodontoonychodysplasia-syndactyly, focal facial dermal dysplasia, KID syndrome, pure hair and nail ectodermal dysplasia, circumscribed palmoplantar hypokeratosis, trichodysplasia-amelogenesis imperfecta syndrome, dermotrichic syndrome, alves Castelo dos Santos syndrome, Brunoni syndrome, ectodermal dysplasia Bartalos type, ectodermal dysplasia margarita type, ectodermal dysplasia alopecia preaxial polydactyly, ectodermal dysplasia arthrogryposis diabetes mellitus, ectodermal dysplasia blindness, ectodermal dysplasia neurosensory deafness, ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, ectodermal dysplasia 15, hypohidrotic/hair type, linear hypopigmentation and craniofacial asymmetry with acral, ocular and brain anomalies, jones hersh yusk syndrome, ectodermal dysplasia 13, hair/tooth type, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ectodermal dysplasia WNT10A related, CTSC-related disorder, ectodermal dysplasia 17 with or without limb malformations

Subtypes (4): ectodermal dysplasia and immune deficiency, X-linked hypohidrotic ectodermal dysplasia, autosomal dominant hypohidrotic ectodermal dysplasia, autosomal recessive hypohidrotic ectodermal dysplasia

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

162 retrieved; paginated sample, class counts are floors:

89 uncertain significance, 36 benign, 20 benign/likely benign, 9 conflicting classifications of pathogenicity, 8 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
261571	NM_022336.4(EDAR):c.1138A>C (p.Ser380Arg)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
261572	NM_022336.4(EDAR):c.319A>G (p.Met107Val)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285382	NM_022336.4(EDAR):c.224C>T (p.Pro75Leu)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330707	NM_022336.4(EDAR):c.844C>T (p.Arg282Trp)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330711	NM_022336.4(EDAR):c.146C>T (p.Pro49Leu)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330712	NM_022336.4(EDAR):c.68C>T (p.Ser23Leu)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296448	NM_145861.4(EDARADD):c.115A>G (p.Asn39Asp)	EDARADD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
265114	NM_022336.4(EDAR):c.463G>A (p.Ala155Thr)	RANBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4462	NM_025216.3(WNT10A):c.682T>A (p.Phe228Ile)	WNT10A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330687	NM_022336.4(EDAR):c.*1761G>A	EDAR	Uncertain significance	criteria provided, single submitter
330689	NM_022336.4(EDAR):c.*1535C>T	EDAR	Uncertain significance	criteria provided, single submitter
330690	NM_022336.4(EDAR):c.*1319C>G	EDAR	Uncertain significance	criteria provided, single submitter
330692	NM_022336.4(EDAR):c.*1226A>C	EDAR	Uncertain significance	criteria provided, single submitter
330693	NM_022336.4(EDAR):c.*1181C>T	EDAR	Uncertain significance	criteria provided, single submitter
330700	NM_022336.4(EDAR):c.*625C>A	EDAR	Uncertain significance	criteria provided, single submitter
330701	NM_022336.4(EDAR):c.*602T>A	EDAR	Uncertain significance	criteria provided, single submitter
330702	NM_022336.4(EDAR):c.*499C>T	EDAR	Uncertain significance	criteria provided, single submitter
330704	NM_022336.4(EDAR):c.*188G>C	EDAR	Uncertain significance	criteria provided, single submitter
330705	NM_022336.4(EDAR):c.1288G>A (p.Asp430Asn)	EDAR	Uncertain significance	criteria provided, single submitter
330706	NM_022336.4(EDAR):c.1183A>G (p.Met395Val)	EDAR	Uncertain significance	criteria provided, single submitter
330708	NM_022336.4(EDAR):c.674C>T (p.Pro225Leu)	EDAR	Uncertain significance	criteria provided, multiple submitters, no conflicts
330709	NM_022336.4(EDAR):c.607G>A (p.Val203Ile)	EDAR	Uncertain significance	criteria provided, multiple submitters, no conflicts
330710	NM_022336.4(EDAR):c.186C>T (p.Tyr62=)	EDAR	Uncertain significance	criteria provided, single submitter
330713	NM_022336.4(EDAR):c.-4G>A	EDAR	Uncertain significance	criteria provided, single submitter
330714	NM_022336.4(EDAR):c.-30A>C	EDAR	Uncertain significance	criteria provided, single submitter
330715	NM_022336.4(EDAR):c.-129G>T	EDAR	Uncertain significance	criteria provided, single submitter
330717	NM_022336.4(EDAR):c.-226T>C	EDAR	Uncertain significance	criteria provided, single submitter
330718	NM_022336.4(EDAR):c.-235G>A	EDAR	Uncertain significance	criteria provided, single submitter
330719	NM_022336.4(EDAR):c.-238C>T	EDAR	Uncertain significance	criteria provided, single submitter
862820	NM_022336.4(EDAR):c.802A>T (p.Ser268Cys)	EDAR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 12 · 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
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
WNT10A	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
WNT10A	Orphanet:2721	Odonto-onycho-dermal dysplasia
WNT10A	Orphanet:50944	Schöpf-Schulz-Passarge syndrome
WNT10A	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
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	gencc,clinvar
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	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)
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.
WNT10A	Protein Wnt-10a	Ligand for members of the frizzled family of seven transmembrane receptors.
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)
EDARADD	Other/Unknown	no		Death_dom, DEATH-like_dom_sf, EDARADD
EDAR	Other/Unknown	no		DEATH-like_dom_sf, EDAR_N, TNR19/27/EDAR
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS
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
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
bone marrow cell	1
lower esophagus mucosa	1
primordial germ cell in gonad	1
endothelial cell	1
mucosa of paranasal sinus	1
sperm	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
WNT10A	151	broad	marker	primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell
RANBP2	294	ubiquitous	marker	endothelial cell, sperm, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RANBP2	7,348
EDAR	1,307
WNT10A	1,092
EDARADD	659

Intra-cohort edges

A	B	Sources
EDAR	EDARADD	biogrid_interaction, intact, string_interaction
EDAR	WNT10A	string_interaction
EDARADD	WNT10A	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
WNT10A	Q9GZT5	82.36
EDARADD	Q8WWZ3	73.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 4 evidence-associated genes (4 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 4 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	196.9×	0.001	EDARADD, EDAR
WNT ligand biogenesis and trafficking	1	105.7×	0.030	WNT10A
IPs transport between nucleus and cytosol	1	95.2×	0.030	RANBP2
IP3 and IP4 transport between cytosol and nucleus	1	95.2×	0.030	RANBP2
IP6 and IP7 transport between cytosol and nucleus	1	95.2×	0.030	RANBP2
Transport of Ribonucleoproteins into the Host Nucleus	1	89.2×	0.030	RANBP2
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	89.2×	0.030	RANBP2
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	89.2×	0.030	RANBP2
NEP/NS2 Interacts with the Cellular Export Machinery	1	86.5×	0.030	RANBP2
Nuclear import of Rev protein	1	84.0×	0.030	RANBP2
Vpr-mediated nuclear import of PICs	1	84.0×	0.030	RANBP2
Transport of the SLBP independent Mature mRNA	1	81.6×	0.030	RANBP2
SUMOylation of SUMOylation proteins	1	81.6×	0.030	RANBP2
Transport of the SLBP Dependant Mature mRNA	1	79.3×	0.030	RANBP2
Rev-mediated nuclear export of HIV RNA	1	79.3×	0.030	RANBP2
Nuclear Pore Complex (NPC) Disassembly	1	77.2×	0.030	RANBP2
SUMOylation of ubiquitinylation proteins	1	73.2×	0.030	RANBP2
NS1 Mediated Effects on Host Pathways	1	71.4×	0.030	RANBP2
Transport of Mature mRNA Derived from an Intronless Transcript	1	68.0×	0.030	RANBP2
Viral Messenger RNA Synthesis	1	64.9×	0.030	RANBP2
SUMOylation of DNA replication proteins	1	62.1×	0.030	RANBP2
SUMOylation of RNA binding proteins	1	59.5×	0.030	RANBP2
snRNP Assembly	1	52.9×	0.033	RANBP2
tRNA processing in the nucleus	1	49.2×	0.033	RANBP2
Class B/2 (Secretin family receptors)	1	47.6×	0.033	WNT10A
SUMOylation of chromatin organization proteins	1	39.6×	0.036	RANBP2
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	38.1×	0.036	RANBP2
ISG15 antiviral mechanism	1	37.6×	0.036	RANBP2
Signaling by ALK fusions and activated point mutants	1	37.6×	0.036	RANBP2
SUMOylation of DNA damage response and repair proteins	1	36.6×	0.036	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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hair follicle development	2	191.5×	0.001	EDAR, WNT10A
salivary gland cavitation	1	842.6×	0.011	EDAR
epidermis morphogenesis	1	702.2×	0.011	WNT10A
regulation of odontogenesis of dentin-containing tooth	1	601.9×	0.011	WNT10A
tongue development	1	526.6×	0.011	WNT10A
sebaceous gland development	1	526.6×	0.011	WNT10A
neural crest cell differentiation	1	383.0×	0.012	WNT10A
nuclear export	1	383.0×	0.012	RANBP2
regulation of gluconeogenesis	1	280.9×	0.014	RANBP2
positive regulation of gene expression	2	19.4×	0.014	EDAR, WNT10A
centrosome localization	1	221.7×	0.015	RANBP2
NLS-bearing protein import into nucleus	1	200.6×	0.015	RANBP2
pigmentation	1	175.5×	0.016	EDAR
intracellular glucose homeostasis	1	145.3×	0.016	RANBP2
odontogenesis	1	131.7×	0.016	WNT10A
response to amphetamine	1	123.9×	0.016	RANBP2
hair follicle morphogenesis	1	123.9×	0.016	WNT10A
cell differentiation	2	14.6×	0.016	EDARADD, EDAR
skin development	1	110.9×	0.017	WNT10A
nucleocytoplasmic transport	1	98.0×	0.018	RANBP2
protein sumoylation	1	81.0×	0.021	RANBP2
odontogenesis of dentin-containing tooth	1	75.2×	0.021	EDAR
cell fate commitment	1	73.9×	0.021	WNT10A
cellular response to transforming growth factor beta stimulus	1	69.1×	0.022	WNT10A
mRNA transport	1	65.8×	0.022	RANBP2
positive regulation of non-canonical NF-kappaB signal transduction	1	63.8×	0.022	EDAR
epidermis development	1	52.7×	0.025	EDAR
positive regulation of JNK cascade	1	40.9×	0.031	EDAR
canonical Wnt signaling pathway	1	38.3×	0.032	WNT10A
cytokine-mediated signaling pathway	1	32.7×	0.036	EDAR

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
EDARADD	0	0
EDAR	0	0
WNT10A	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	EDARADD, EDAR, WNT10A, 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)
EDARADD	0	—
EDAR	1	—
WNT10A	0	—
RANBP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01109290	Not specified	COMPLETED	Characterization of Sweat Gland Function in Patients With Recessively Inherited Hypohidrotic Ectodermal Dysplasia
NCT01293565	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected by Hypohidrotic Ectodermal Dysplasia - A
NCT01386775	Not specified	COMPLETED	Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia: Intrafamilial Variation
NCT01398397	Not specified	COMPLETED	Medical Record Review of Hypohidrotic Ectodermal Dysplasia Clinical Phenotype
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