Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis

Summary

Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (MONDO:0032584) is a disease caused by TSPEAR (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: TSPEAR (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 40

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
Mondo ID	MONDO:0032584
OMIM	618180
Orphanet	685067
DOID	DOID:0111662
UMLS	C4748560
MedGen	1648329
GARD	0025707
Is cancer (heuristic)	no

Also known as: ECTD14

Data availability: 40 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis

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, hypohidrotic ectodermal dysplasia, 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 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

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

40 retrieved; paginated sample, class counts are floors:

12 pathogenic, 9 conflicting classifications of pathogenicity, 7 uncertain significance, 6 pathogenic/likely pathogenic, 3 benign, 2 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
584443	NM_144991.3(TSPEAR):c.1726_1728delinsTT (p.Val576fs)	LOC126653398	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
817061	NM_144991.3(TSPEAR):c.1676_1677del (p.Tyr559fs)	LOC126653398	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1030229	NM_144991.3(TSPEAR):c.789T>G (p.Tyr263Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
1311928	NM_144991.3(TSPEAR):c.430C>T (p.Arg144Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
1705559	NM_144991.3(TSPEAR):c.1785AGA[1] (p.Glu596del)	TSPEAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1801840	NM_144991.3(TSPEAR):c.1423G>C (p.Gly475Arg)	TSPEAR	Pathogenic	no assertion criteria provided
1801842	NM_144991.3(TSPEAR):c.48del (p.Gly17fs)	TSPEAR	Pathogenic	no assertion criteria provided
1942560	NM_144991.3(TSPEAR):c.1514C>A (p.Ser505Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2081026	NM_144991.3(TSPEAR):c.1093C>T (p.Gln365Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2136295	NM_144991.3(TSPEAR):c.1178del (p.Pro393fs)	TSPEAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2880629	NM_144991.3(TSPEAR):c.235C>T (p.Gln79Ter)	TSPEAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2891535	NM_144991.3(TSPEAR):c.2T>C (p.Met1Thr)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2986614	NM_144991.3(TSPEAR):c.1463C>A (p.Ser488Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
403572	NM_144991.3(TSPEAR):c.589C>T (p.Arg197Ter)	TSPEAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081842	NM_144991.3(TSPEAR):c.1238_1239del (p.Phe413fs)	TSPEAR	Pathogenic	criteria provided, single submitter
4081843	NM_144991.3(TSPEAR):c.1794T>A (p.Tyr598Ter)	TSPEAR	Pathogenic	criteria provided, single submitter
984376	NM_144991.3(TSPEAR):c.42_51dup (p.His18fs)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
984377	NM_144991.3(TSPEAR):c.1281G>A (p.Trp427Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2664284	NM_144991.3(TSPEAR):c.1594_1595insA (p.Phe532fs)	LOC126653398	Likely pathogenic	criteria provided, single submitter
3780756	NM_144991.3(TSPEAR):c.1448del (p.Ser483fs)	TSPEAR	Likely pathogenic	criteria provided, single submitter
505194	NM_144991.3(TSPEAR):c.1697A>G (p.Tyr566Cys)	LOC126653398	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
597169	NM_144991.3(TSPEAR):c.1754G>T (p.Ser585Ile)	LOC126653398	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1188184	NM_144991.3(TSPEAR):c.1493_1494delinsTG (p.Gly498Val)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197259	NM_144991.3(TSPEAR):c.1877T>C (p.Phe626Ser)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227135	NM_144991.3(TSPEAR):c.1915G>A (p.Asp639Asn)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
493326	NM_144991.3(TSPEAR):c.1870G>T (p.Glu624Ter)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
504870	NM_144991.3(TSPEAR):c.1528C>T (p.Arg510Ter)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
593867	NM_144991.3(TSPEAR):c.1423G>A (p.Gly475Ser)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
594076	NM_144991.3(TSPEAR):c.1469T>A (p.Leu490Gln)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1379649	NM_144991.3(TSPEAR):c.358G>A (p.Gly120Ser)	TSPEAR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 1 · 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
TSPEAR	Strong	Autosomal recessive	ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSPEAR	Orphanet:685067	Hypodontia-scalp hypotrichosis-facial dysmorphism syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSPEAR	HGNC:1268	ENSG00000175894	Q8WU66	Thrombospondin-type laminin G domain and EAR repeat-containing protein	gencc,clinvar
KRTAP10-1	HGNC:22966	ENSG00000215455	P60331	Keratin-associated protein 10-1	clinvar
KRTAP10-3	HGNC:22968	ENSG00000212935	P60369	Keratin-associated protein 10-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSPEAR	Thrombospondin-type laminin G domain and EAR repeat-containing protein	Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.
KRTAP10-1	Keratin-associated protein 10-1	In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through t…
KRTAP10-3	Keratin-associated protein 10-3	In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through t…

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSPEAR	Other/Unknown	no		EPTP, EAR, ConA-like_dom_sf
KRTAP10-1	Other/Unknown	no		KAP
KRTAP10-3	Other/Unknown	no		KAP

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
pituitary gland	1
primordial germ cell in gonad	1
colonic epithelium	1
cortical plate	1
ventricular zone	1
bone marrow cell	1
skin of abdomen	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSPEAR	88	tissue_specific	yes	primordial germ cell in gonad, adenohypophysis, pituitary gland
KRTAP10-1	7		yes	colonic epithelium, ventricular zone, cortical plate
KRTAP10-3	13	tissue_specific	yes	sural nerve, skin of abdomen, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSPEAR	839
KRTAP10-3	486
KRTAP10-1	457

Intra-cohort edges

A	B	Sources
KRTAP10-1	TSPEAR	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPEAR	Q8WU66	87.47
KRTAP10-3	P60369	39.11
KRTAP10-1	P60331	35.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 3 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
Keratinization	2	55.7×	6e-04	KRTAP10-1, KRTAP10-3
Developmental Biology	2	14.5×	0.005	KRTAP10-1, KRTAP10-3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tooth mineralization	1	5617.3×	0.001	TSPEAR
hair cycle process	1	2808.7×	0.001	TSPEAR
regulation of Notch signaling pathway	1	842.6×	0.002	TSPEAR
Notch signaling pathway	1	141.6×	0.011	TSPEAR
sensory perception of sound	1	100.9×	0.012	TSPEAR
signal transduction	1	16.1×	0.062	TSPEAR

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSPEAR	0	0
KRTAP10-1	0	0
KRTAP10-3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	TSPEAR, KRTAP10-1, KRTAP10-3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSPEAR	0	—
KRTAP10-1	0	—
KRTAP10-3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.