Tooth agenesis, selective, 2

Summary

Tooth agenesis, selective, 2 (MONDO:0011265) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, 2
Mondo ID	MONDO:0011265
MeSH	C566513
OMIM	602639
UMLS	C1865092
MedGen	400679
GARD	0024785
Is cancer (heuristic)	no

Also known as: STHAG2 · tooth agenesis, selective, 2

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › tooth agenesis › tooth agenesis, selective, 2

Related subtypes (11): tooth agenesis, selective, 1, tooth agenesis, selective, 4, tooth agenesis, selective, X-linked, 1, tooth agenesis, selective, 3, tooth agenesis, selective, 5, tooth agenesis, selective, 7, tooth agenesis, selective, 8, tooth agenesis, selective, 9, hypodontia/oligodontia with orofacial cleft, tooth agenesis, selective, with orofacial cleft, tooth agenesis, selective, 10

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

4 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2504639	NM_001399.5(EDA):c.878T>G (p.Leu293Arg)	EDA	Pathogenic	criteria provided, single submitter
139576	NM_025216.3(WNT10A):c.637G>A (p.Gly213Ser)	WNT10A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225515	NM_025216.3(WNT10A):c.511C>T (p.Arg171Cys)	WNT10A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2498334	NM_147127.5(EVC2):c.2012T>C (p.Leu671Ser)	EVC2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
EVC2	Orphanet:289	Ellis Van Creveld syndrome
EVC2	Orphanet:952	Acrofacial dysostosis, Weyers type
EDA	Orphanet:181	X-linked hypohidrotic ectodermal dysplasia
EDA	Orphanet:99798	Oligodontia

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
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	clinvar
EVC2	HGNC:19747	ENSG00000173040	Q86UK5	Limbin	clinvar
EDA	HGNC:3157	ENSG00000158813	Q92838	Ectodysplasin-A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT10A	Protein Wnt-10a	Ligand for members of the frizzled family of seven transmembrane receptors.
EVC2	Limbin	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
EDA	Ectodysplasin-A	Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs.

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)
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS
EVC2	Other/Unknown	no		Limbin, Limbin/EVC
EDA	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	2
bone marrow cell	1
lower esophagus mucosa	1
calcaneal tendon	1
pancreatic ductal cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT10A	151	broad	marker	primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell
EVC2	182	ubiquitous	marker	pancreatic ductal cell, calcaneal tendon, primordial germ cell in gonad
EDA	175	broad	marker	tongue squamous epithelium, male germ line stem cell (sensu Vertebrata) in testis, oocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT10A	1,092
EVC2	913
EDA	792

Intra-cohort edges

A	B	Sources
EDA	WNT10A	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EDA	Q92838	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT10A	Q9GZT5	82.36
EVC2	Q86UK5	73.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of SMO	1	211.5×	0.018	EVC2
WNT ligand biogenesis and trafficking	1	141.0×	0.018	WNT10A
TNFs bind their physiological receptors	1	131.3×	0.018	EDA
Class B/2 (Secretin family receptors)	1	63.4×	0.022	WNT10A
Signaling by Hedgehog	1	61.4×	0.022	EVC2
Hedgehog ‘on’ state	1	52.9×	0.022	EVC2
Signal Transduction	1	3.4×	0.267	EVC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
odontogenesis	2	351.1×	3e-04	WNT10A, EDA
canonical Wnt signaling pathway	2	102.1×	0.002	WNT10A, EDA
trachea gland development	1	2808.7×	0.003	EDA
salivary gland cavitation	1	1123.5×	0.005	EDA
hair follicle placode formation	1	1123.5×	0.005	EDA
epidermis morphogenesis	1	936.2×	0.005	WNT10A
regulation of odontogenesis of dentin-containing tooth	1	802.5×	0.005	WNT10A
tongue development	1	702.2×	0.005	WNT10A
sebaceous gland development	1	702.2×	0.005	WNT10A
neural crest cell differentiation	1	510.7×	0.005	WNT10A
regulation of non-canonical NF-kappaB signal transduction	1	510.7×	0.005	EDA
positive regulation of gene expression	2	25.8×	0.005	WNT10A, EDA
pigmentation	1	234.1×	0.010	EDA
hair follicle morphogenesis	1	165.2×	0.013	WNT10A
skin development	1	147.8×	0.013	WNT10A
hair follicle development	1	127.7×	0.014	WNT10A
odontogenesis of dentin-containing tooth	1	100.3×	0.016	EDA
cell fate commitment	1	98.5×	0.016	WNT10A
cellular response to transforming growth factor beta stimulus	1	92.1×	0.017	WNT10A
positive regulation of non-canonical NF-kappaB signal transduction	1	85.1×	0.017	EDA
smoothened signaling pathway	1	60.4×	0.023	EVC2
cell-matrix adhesion	1	54.5×	0.024	EDA
positive regulation of canonical Wnt signaling pathway	1	51.5×	0.024	EDA
cytokine-mediated signaling pathway	1	43.5×	0.028	EDA
neuron differentiation	1	33.4×	0.034	WNT10A
gene expression	1	26.6×	0.041	EDA
positive regulation of canonical NF-kappaB signal transduction	1	24.2×	0.044	EDA
immune response	1	15.7×	0.065	EDA
cell differentiation	1	9.7×	0.100	EDA

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
WNT10A	0	0
EVC2	0	0
EDA	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	WNT10A, EVC2, EDA

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)
WNT10A	0	—
EVC2	0	—
EDA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.