Autosomal recessive hypohidrotic ectodermal dysplasia

Summary

Autosomal recessive hypohidrotic ectodermal dysplasia (MONDO:0016619) is a disease with 6 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 6
• ClinVar variants: 174
• Phenotypes (HPO): 10

Clinical features

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0000958	Dry skin	Very frequent (80-99%)
HP:0001231	Abnormal fingernail morphology	Very frequent (80-99%)
HP:0002213	Fine hair	Very frequent (80-99%)
HP:0006323	Premature loss of primary teeth	Very frequent (80-99%)
HP:0008388	Abnormal toenail morphology	Very frequent (80-99%)
HP:0000685	Hypoplasia of teeth	Very frequent (80-99%)
HP:0001595	Abnormality of the hair	Very frequent (80-99%)
HP:0000966	Hypohidrosis	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0006482	Abnormal dental morphology	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive hypohidrotic ectodermal dysplasia
Mondo ID	MONDO:0016619
MeSH	D053360
Orphanet	248
ICD-11	7083042
NCIT	C84580
SNOMED CT	27025001
UMLS	C0406702
MedGen	96067
GARD	0002057
Is cancer (heuristic)	no

Also known as: anhidrotic ectodermal dysplasia, autosomal recessive · AR-HED · autosomal recessive anhidrotic ectodermal dysplasia · hypohidrotic ectodermal dysplasia autosomal recessive · hypohidrotic ectodermal dysplasia, autosomal recessive

Data availability: 174 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 recessive disease › autosomal recessive hypohidrotic ectodermal dysplasia

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Subtypes (2): ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive, ectodermal dysplasia 11B, 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

174 retrieved; paginated sample, class counts are floors:

60 uncertain significance, 35 pathogenic, 24 likely benign, 16 conflicting classifications of pathogenicity, 15 benign, 11 likely pathogenic, 7 benign/likely benign, 6 pathogenic/likely pathogenic

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
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
5852	NM_022336.4(EDAR):c.1072C>T (p.Arg358Ter)	EDAR	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 32 · Orphanet: 14 · 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
WNT10A	Definitive	Semidominant	ectodermal dysplasia WNT10A related	10
EDARADD	Strong	Autosomal dominant	ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant	9
CSTB	Supportive	Autosomal recessive	autosomal recessive hypohidrotic ectodermal dysplasia	4

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
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
EDARADD	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:99798	Oligodontia
CSTB	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
CSTB	Orphanet:308	Progressive myoclonic epilepsy type 1
RANBP2	Orphanet:178342	Inflammatory myofibroblastic tumor
RANBP2	Orphanet:263524	Acute necrotizing encephalopathy of childhood
RANBP2	Orphanet:88619	Familial acute necrotizing encephalopathy

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EDAR	HGNC:2895	ENSG00000135960	Q9UNE0	Tumor necrosis factor receptor superfamily member EDAR	gencc,clinvar
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	gencc
EDARADD	HGNC:14341	ENSG00000186197	Q8WWZ3	Ectodysplasin-A receptor-associated adapter protein	gencc
CSTB	HGNC:2482	ENSG00000160213	P04080	Cystatin-B	gencc
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.
WNT10A	Protein Wnt-10a	Ligand for members of the frizzled family of seven transmembrane receptors.
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.
CSTB	Cystatin-B	This is an intracellular thiol proteinase inhibitor.
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: 5 · 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	5	1.5×	0.348
Transcription factor	1	1.4×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EDAR	Other/Unknown	no		DEATH-like_dom_sf, EDAR_N, TNR19/27/EDAR
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS
EDARADD	Other/Unknown	no		Death_dom, DEATH-like_dom_sf, EDARADD
CSTB	Other/Unknown	no		Cystatin_dom, Prot_inh_stefin, Prot_inh_cystat_CS
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.

5 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	2
male germ line stem cell (sensu Vertebrata) in testis	2
sperm	2
oocyte	1
pancreatic ductal cell	1
secondary oocyte	1
bone marrow cell	1
primordial germ cell in gonad	1
islet of Langerhans	1
sural nerve	1
pharyngeal mucosa	1
tongue squamous epithelium	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
WNT10A	151	broad	marker	primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell
EDARADD	147	broad	marker	islet of Langerhans, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
CSTB	300	ubiquitous	marker	lower esophagus mucosa, tongue squamous epithelium, pharyngeal mucosa
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: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RANBP2	7,348
CSTB	1,987
EDAR	1,307
WNT10A	1,092
CCDC138	829
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: 3 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RANBP2	P49792	33
CSTB	P04080	3
EDAR	Q9UNE0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT10A	Q9GZT5	82.36
EDARADD	Q8WWZ3	73.81
CCDC138	Q96M89	73.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 41. Enrichment computed across 6 evidence-associated genes (5 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 5 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	157.5×	0.003	EDAR, EDARADD
WNT ligand biogenesis and trafficking	1	84.6×	0.039	WNT10A
IPs transport between nucleus and cytosol	1	76.1×	0.039	RANBP2
IP3 and IP4 transport between cytosol and nucleus	1	76.1×	0.039	RANBP2
IP6 and IP7 transport between cytosol and nucleus	1	76.1×	0.039	RANBP2
Transport of Ribonucleoproteins into the Host Nucleus	1	71.4×	0.039	RANBP2
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	71.4×	0.039	RANBP2
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	71.4×	0.039	RANBP2
NEP/NS2 Interacts with the Cellular Export Machinery	1	69.2×	0.039	RANBP2
Nuclear import of Rev protein	1	67.2×	0.039	RANBP2
Vpr-mediated nuclear import of PICs	1	67.2×	0.039	RANBP2
Transport of the SLBP independent Mature mRNA	1	65.3×	0.039	RANBP2
SUMOylation of SUMOylation proteins	1	65.3×	0.039	RANBP2
Transport of the SLBP Dependant Mature mRNA	1	63.4×	0.039	RANBP2
Rev-mediated nuclear export of HIV RNA	1	63.4×	0.039	RANBP2
Nuclear Pore Complex (NPC) Disassembly	1	61.7×	0.039	RANBP2
SUMOylation of ubiquitinylation proteins	1	58.6×	0.039	RANBP2
NS1 Mediated Effects on Host Pathways	1	57.1×	0.039	RANBP2
Transport of Mature mRNA Derived from an Intronless Transcript	1	54.4×	0.039	RANBP2
Viral Messenger RNA Synthesis	1	51.9×	0.039	RANBP2
SUMOylation of DNA replication proteins	1	49.6×	0.039	RANBP2
SUMOylation of RNA binding proteins	1	47.6×	0.039	RANBP2
snRNP Assembly	1	42.3×	0.042	RANBP2
tRNA processing in the nucleus	1	39.4×	0.043	RANBP2
Class B/2 (Secretin family receptors)	1	38.1×	0.043	WNT10A
SUMOylation of chromatin organization proteins	1	31.7×	0.046	RANBP2
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	30.4×	0.046	RANBP2
ISG15 antiviral mechanism	1	30.1×	0.046	RANBP2
Signaling by ALK fusions and activated point mutants	1	30.1×	0.046	RANBP2
SUMOylation of DNA damage response and repair proteins	1	29.3×	0.046	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
hair follicle development	2	153.2×	0.003	EDAR, WNT10A
salivary gland cavitation	1	674.1×	0.015	EDAR
epidermis morphogenesis	1	561.7×	0.015	WNT10A
regulation of odontogenesis of dentin-containing tooth	1	481.5×	0.015	WNT10A
tongue development	1	421.3×	0.015	WNT10A
sebaceous gland development	1	421.3×	0.015	WNT10A
neural crest cell differentiation	1	306.4×	0.015	WNT10A
nuclear export	1	306.4×	0.015	RANBP2
regulation of gluconeogenesis	1	224.7×	0.019	RANBP2
centrosome localization	1	177.4×	0.020	RANBP2
NLS-bearing protein import into nucleus	1	160.5×	0.020	RANBP2
positive regulation of gene expression	2	15.5×	0.020	EDAR, WNT10A
pigmentation	1	140.4×	0.020	EDAR
negative regulation of proteolysis	1	134.8×	0.020	CSTB
intracellular glucose homeostasis	1	116.2×	0.021	RANBP2
odontogenesis	1	105.3×	0.021	WNT10A
response to amphetamine	1	99.1×	0.021	RANBP2
hair follicle morphogenesis	1	99.1×	0.021	WNT10A
skin development	1	88.7×	0.021	WNT10A
cell differentiation	2	11.6×	0.021	EDAR, EDARADD
nucleocytoplasmic transport	1	78.4×	0.023	RANBP2
protein sumoylation	1	64.8×	0.026	RANBP2
adult locomotory behavior	1	60.2×	0.026	CSTB
odontogenesis of dentin-containing tooth	1	60.2×	0.026	EDAR
cell fate commitment	1	59.1×	0.026	WNT10A
cellular response to transforming growth factor beta stimulus	1	55.2×	0.026	WNT10A
mRNA transport	1	52.7×	0.026	RANBP2
positive regulation of non-canonical NF-kappaB signal transduction	1	51.1×	0.026	EDAR
epidermis development	1	42.1×	0.031	EDAR
positive regulation of JNK cascade	1	32.7×	0.038	EDAR

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 3 of 6 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
WNT10A	0	0
EDARADD	0	0
CSTB	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
CSTB	1	Binding:1
RANBP2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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	6	EDAR, WNT10A, EDARADD, CSTB, CCDC138, RANBP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EDAR	1	—
WNT10A	0	—
EDARADD	0	—
CSTB	1	—
CCDC138	0	—
RANBP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.