Autosomal dominant hypohidrotic ectodermal dysplasia

Summary

Autosomal dominant hypohidrotic ectodermal dysplasia (MONDO:0015884) is a disease with 5 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 2
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000668	Hypodontia	Very frequent (80-99%)
HP:0000963	Thin skin	Very frequent (80-99%)
HP:0000966	Hypohidrosis	Very frequent (80-99%)
HP:0002231	Sparse body hair	Very frequent (80-99%)
HP:0006323	Premature loss of primary teeth	Very frequent (80-99%)
HP:0006482	Abnormal dental morphology	Very frequent (80-99%)
HP:0008070	Sparse hair	Very frequent (80-99%)
HP:0001231	Abnormal fingernail morphology	Frequent (30-79%)
HP:0000457	Depressed nasal ridge	Occasional (5-29%)
HP:0000964	Eczematoid dermatitis	Occasional (5-29%)
HP:0001000	Abnormality of skin pigmentation	Occasional (5-29%)
HP:0002047	Malignant hyperthermia	Occasional (5-29%)
HP:0011220	Prominent forehead	Occasional (5-29%)
HP:0012471	Thick vermilion border	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant hypohidrotic ectodermal dysplasia
Mondo ID	MONDO:0015884
Orphanet	1810
ICD-11	222258115
UMLS	C0265331
MedGen	539190
GARD	0002048
Is cancer (heuristic)	no

Also known as: AD-HED · autosomal dominant anhidrotic ectodermal dysplasia · hypohidrotic ectodermal dysplasia, autosomal dominant

Data availability: 2 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, 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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
228341	NC_000002.12:g.(?108910426)(108912698_?)del	EDAR	Pathogenic	criteria provided, single submitter
163325	NM_022336.3(EDAR):c.(?998)(1347_?)del	RANBP2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 23 · Orphanet: 10 · 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
KDF1	Definitive	Autosomal dominant	ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type	4
EDARADD	Strong	Autosomal dominant	ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant	9
TRAF6	Supportive	Autosomal dominant	autosomal dominant hypohidrotic ectodermal dysplasia

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
TRAF6	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:99798	Oligodontia
KDF1	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
RANBP2	Orphanet:178342	Inflammatory myofibroblastic tumor
RANBP2	Orphanet:263524	Acute necrotizing encephalopathy of childhood
RANBP2	Orphanet:88619	Familial acute necrotizing encephalopathy

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EDAR	HGNC:2895	ENSG00000135960	Q9UNE0	Tumor necrosis factor receptor superfamily member EDAR	gencc,clinvar
TRAF6	HGNC:12036	ENSG00000175104	Q9Y4K3	TNF receptor-associated factor 6	gencc
EDARADD	HGNC:14341	ENSG00000186197	Q8WWZ3	Ectodysplasin-A receptor-associated adapter protein	gencc
KDF1	HGNC:26624	ENSG00000175707	Q8NAX2	Keratinocyte differentiation factor 1	gencc
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.
TRAF6	TNF receptor-associated factor 6	E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of ‘Lys-63’-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2.
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.
KDF1	Keratinocyte differentiation factor 1	Plays a role in the regulation of the epidermis formation during early development.
RANBP2	E3 SUMO-protein ligase RanBP2	E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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	2	3.3×	0.229
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EDAR	Other/Unknown	no		DEATH-like_dom_sf, EDAR_N, TNR19/27/EDAR
TRAF6	Transcription factor	no		Znf_TRAF, Znf_RING, MATH/TRAF_dom
EDARADD	Other/Unknown	no		Death_dom, DEATH-like_dom_sf, EDARADD
KDF1	Other/Unknown	no		KDF1
RANBP2	Transcription factor	no		Ran_bind_dom, Znf_RanBP2, Cyclophilin-type_PPIase_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	2
endothelial cell	2
oocyte	1
pancreatic ductal cell	1
primordial germ cell in gonad	1
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
esophagus mucosa	1
lower esophagus mucosa	1
mucosa of transverse colon	1
mucosa of paranasal sinus	1
sperm	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
TRAF6	235	ubiquitous	marker	secondary oocyte, endothelial cell, primordial germ cell in gonad
EDARADD	147	broad	marker	islet of Langerhans, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
KDF1	163	broad	marker	mucosa of transverse colon, lower esophagus mucosa, esophagus mucosa
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
TRAF6	6,163
EDAR	1,307
KDF1	1,041
EDARADD	659

Intra-cohort edges

A	B	Sources
EDAR	EDARADD	biogrid_interaction, intact, string_interaction
EDAR	TRAF6	string_interaction
EDARADD	TRAF6	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RANBP2	P49792	33
TRAF6	Q9Y4K3	13
EDAR	Q9UNE0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EDARADD	Q8WWZ3	73.81
KDF1	Q8NAX2	59.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 72. Enrichment computed across 5 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×	0.003	EDAR, EDARADD
IRAK2 mediated activation of TAK1 complex	1	285.5×	0.025	TRAF6
Regulated proteolysis of p75NTR	1	259.6×	0.025	TRAF6
TICAM1,TRAF6-dependent induction of TAK1 complex	1	259.6×	0.025	TRAF6
Alpha-protein kinase 1 signaling pathway	1	259.6×	0.025	TRAF6
p75NTR recruits signalling complexes	1	219.6×	0.025	TRAF6
NF-kB is activated and signals survival	1	219.6×	0.025	TRAF6
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	1	219.6×	0.025	TRAF6
IRAK1 recruits IKK complex	1	203.9×	0.025	TRAF6
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation	1	203.9×	0.025	TRAF6
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	1	190.3×	0.025	TRAF6
NRIF signals cell death from the nucleus	1	178.4×	0.025	TRAF6
TRAF6-mediated induction of TAK1 complex within TLR4 complex	1	178.4×	0.025	TRAF6
Regulation of NF-kappa B signaling	1	158.6×	0.025	TRAF6
TICAM1, RIP1-mediated IKK complex recruitment	1	150.3×	0.025	TRAF6
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	1	129.8×	0.025	TRAF6
activated TAK1 mediates p38 MAPK activation	1	124.1×	0.025	TRAF6
IKK complex recruitment mediated by RIP1	1	124.1×	0.025	TRAF6
TRAF6 mediated NF-kB activation	1	114.2×	0.025	TRAF6
IPs transport between nucleus and cytosol	1	95.2×	0.025	RANBP2
IP3 and IP4 transport between cytosol and nucleus	1	95.2×	0.025	RANBP2
IP6 and IP7 transport between cytosol and nucleus	1	95.2×	0.025	RANBP2
TRAF6 mediated IRF7 activation	1	95.2×	0.025	TRAF6
Transport of Ribonucleoproteins into the Host Nucleus	1	89.2×	0.025	RANBP2
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	89.2×	0.025	RANBP2
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	89.2×	0.025	RANBP2
NEP/NS2 Interacts with the Cellular Export Machinery	1	86.5×	0.025	RANBP2
Nuclear import of Rev protein	1	84.0×	0.025	RANBP2
Vpr-mediated nuclear import of PICs	1	84.0×	0.025	RANBP2
Transport of the SLBP independent Mature mRNA	1	81.6×	0.025	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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
odontogenesis of dentin-containing tooth	2	120.4×	0.010	EDAR, TRAF6
limb epidermis development	1	1685.2×	0.016	KDF1
regulation of epidermal cell division	1	1123.5×	0.016	KDF1
salivary gland cavitation	1	674.1×	0.016	EDAR
interleukin-17A-mediated signaling pathway	1	561.7×	0.016	TRAF6
regulation of immunoglobulin production	1	481.5×	0.016	TRAF6
interleukin-33-mediated signaling pathway	1	421.3×	0.016	TRAF6
positive regulation of epidermal cell differentiation	1	421.3×	0.016	KDF1
T-helper 1 type immune response	1	374.5×	0.016	TRAF6
CD40 signaling pathway	1	337.0×	0.016	TRAF6
interleukin-17-mediated signaling pathway	1	337.0×	0.016	TRAF6
keratinocyte development	1	306.4×	0.016	KDF1
morphogenesis of embryonic epithelium	1	306.4×	0.016	KDF1
positive regulation of lipopolysaccharide-mediated signaling pathway	1	306.4×	0.016	TRAF6
activation of protein kinase activity	1	306.4×	0.016	TRAF6
TRIF-dependent toll-like receptor signaling pathway	1	306.4×	0.016	TRAF6
nuclear export	1	306.4×	0.016	RANBP2
positive regulation of JNK cascade	2	65.4×	0.016	EDAR, TRAF6
positive regulation of canonical NF-kappaB signal transduction	2	29.1×	0.016	EDAR, TRAF6
positive regulation of leukocyte adhesion to vascular endothelial cell	1	280.9×	0.016	TRAF6
positive regulation of T cell cytokine production	1	259.3×	0.016	TRAF6
positive regulation of JUN kinase activity	1	259.3×	0.016	TRAF6
regulation of gluconeogenesis	1	224.7×	0.017	RANBP2
toll-like receptor 3 signaling pathway	1	224.7×	0.017	TRAF6
MyD88-dependent toll-like receptor signaling pathway	1	187.2×	0.017	TRAF6
myeloid dendritic cell differentiation	1	187.2×	0.017	TRAF6
cytoplasmic pattern recognition receptor signaling pathway	1	177.4×	0.017	TRAF6
centrosome localization	1	177.4×	0.017	RANBP2
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	177.4×	0.017	TRAF6
non-canonical NF-kappaB signal transduction	1	168.5×	0.017	TRAF6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
TRAF6	0	0
EDARADD	0	0
KDF1	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
TRAF6	6	Binding:6
EDAR	1	Binding:1
RANBP2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	5	EDAR, TRAF6, EDARADD, KDF1, RANBP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EDAR	1	—
TRAF6	6	—
EDARADD	0	—
KDF1	0	—
RANBP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.