Ectodermal dysplasia 17 with or without limb malformations

Summary

Ectodermal dysplasia 17 with or without limb malformations (MONDO:0979228) is a disease caused by LEF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LEF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia 17 with or without limb malformations
Mondo ID	MONDO:0979228
OMIM	621224
UMLS	C6012731
MedGen	1876515
GARD	0028106
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › ectodermal dysplasia 17 with or without limb malformations

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 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

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

6 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322007	NM_016269.5(LEF1):c.1042TAT[1] (p.Tyr349del)	LEF1	Pathogenic	criteria provided, single submitter
1322008	NM_016269.5(LEF1):c.544del (p.Gln182fs)	LEF1	Pathogenic	criteria provided, single submitter
3901232	NM_016269.5(LEF1):c.856del (p.His286fs)	LEF1	Pathogenic	no assertion criteria provided
3377105	NM_016269.5(LEF1):c.513del (p.Ser172fs)	LEF1	Likely pathogenic	criteria provided, single submitter
4531918	NM_016269.5(LEF1):c.469dup (p.Leu157fs)	LEF1	Likely pathogenic	criteria provided, single submitter
1322009	NM_016269.5(LEF1):c.928A>G (p.Met310Val)	LEF1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
LEF1	Strong	Autosomal dominant	ectodermal dysplasia 17 with or without limb malformations	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LEF1	Orphanet:708043	Ectodermal dysplasia with oligodontia-hand and foot malformation-hypoplastic nipples

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LEF1	HGNC:6551	ENSG00000138795	Q9UJU2	Lymphoid enhancer-binding factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LEF1	Lymphoid enhancer-binding factor 1	Transcription factor that binds DNA in a sequence-specific manner.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LEF1	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lymph node	1
thymus	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LEF1	258	broad	marker	thymus, lymph node, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LEF1	4,164

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LEF1	Q9UJU2	57.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	1142.0×	0.009	LEF1
RUNX3 regulates WNT signaling	1	1142.0×	0.009	LEF1
Formation of axial mesoderm	1	815.7×	0.009	LEF1
Repression of WNT target genes	1	713.8×	0.009	LEF1
Germ layer formation at gastrulation	1	671.8×	0.009	LEF1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	571.0×	0.009	LEF1
Cardiogenesis	1	423.0×	0.009	LEF1
Formation of paraxial mesoderm	1	407.9×	0.009	LEF1
Beta-catenin independent WNT signaling	1	292.8×	0.009	LEF1
Transcriptional regulation by RUNX3	1	271.9×	0.009	LEF1
Transcriptional Regulation by VENTX	1	265.6×	0.009	LEF1
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.009	LEF1
Gastrulation	1	259.6×	0.009	LEF1
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.009	LEF1
Somitogenesis	1	233.1×	0.009	LEF1
MITF-M-dependent gene expression	1	181.3×	0.009	LEF1
Ca2+ pathway	1	178.4×	0.009	LEF1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.009	LEF1
Degradation of beta-catenin by the destruction complex	1	173.0×	0.009	LEF1
Transcriptional regulation of granulopoiesis	1	125.5×	0.011	LEF1
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.011	LEF1
TCF dependent signaling in response to WNT	1	117.7×	0.011	LEF1
MITF-M-regulated melanocyte development	1	114.2×	0.011	LEF1
Signaling by WNT	1	112.0×	0.011	LEF1
Regulation of PD-L1(CD274) transcription	1	108.8×	0.011	LEF1
RNA Polymerase II Transcription	1	22.5×	0.051	LEF1
Gene expression (Transcription)	1	17.8×	0.062	LEF1
Generic Transcription Pathway	1	15.1×	0.071	LEF1
Developmental Biology	1	14.5×	0.072	LEF1
Signal Transduction	1	10.2×	0.098	LEF1

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
forebrain neuroblast division	1	8426.0×	0.001	LEF1
trachea gland development	1	8426.0×	0.001	LEF1
negative regulation of apoptotic process in bone marrow cell	1	5617.3×	0.001	LEF1
formation of radial glial scaffolds	1	4213.0×	0.001	LEF1
T cell receptor V(D)J recombination	1	4213.0×	0.001	LEF1
positive regulation of cell proliferation in bone marrow	1	4213.0×	0.001	LEF1
negative regulation of striated muscle tissue development	1	3370.4×	0.001	LEF1
paraxial mesoderm formation	1	3370.4×	0.001	LEF1
anatomical structure regression	1	3370.4×	0.001	LEF1
forebrain radial glial cell differentiation	1	2808.7×	0.001	LEF1
positive regulation of granulocyte differentiation	1	2808.7×	0.001	LEF1
positive regulation of cell cycle process	1	2808.7×	0.001	LEF1
apoptotic process involved in blood vessel morphogenesis	1	2808.7×	0.001	LEF1
negative regulation of interleukin-13 production	1	2407.4×	0.001	LEF1
negative regulation of interleukin-4 production	1	2407.4×	0.001	LEF1
positive regulation of odontoblast differentiation	1	2407.4×	0.001	LEF1
tongue development	1	2106.5×	0.001	LEF1
chorio-allantoic fusion	1	2106.5×	0.001	LEF1
positive regulation of endothelial cell-matrix adhesion	1	2106.5×	0.001	LEF1
neutrophil differentiation	1	1872.4×	0.001	LEF1
negative regulation of interleukin-5 production	1	1872.4×	0.001	LEF1
positive regulation of gamma-delta T cell differentiation	1	1872.4×	0.001	LEF1
positive regulation of chondrocyte proliferation	1	1872.4×	0.001	LEF1
T-helper 1 cell differentiation	1	1532.0×	0.002	LEF1
secondary palate development	1	1203.7×	0.002	LEF1
negative regulation of DNA binding	1	1123.5×	0.002	LEF1
sensory perception of taste	1	1123.5×	0.002	LEF1
host-mediated activation of viral transcription	1	887.0×	0.002	LEF1
epithelial cell apoptotic process	1	842.6×	0.002	LEF1
mammary gland development	1	648.1×	0.003	LEF1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LEF1	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
LEF1	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	LEF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LEF1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.