Tooth agenesis, selective, 4

Summary

Tooth agenesis, selective, 4 (MONDO:0007881) is a disease caused by WNT10A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: WNT10A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 501

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, 4
Mondo ID	MONDO:0007881
MeSH	C563634
OMIM	150400
UMLS	C1835492
MedGen	372057
GARD	0018245
Is cancer (heuristic)	no

Also known as: STHAG4 · tooth agenesis caused by mutation in WNT10A · tooth agenesis, selective, 4 · tooth agenesis, selective, type 4 · WNT10A tooth agenesis

Data availability: 501 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › tooth agenesis › tooth agenesis, selective, 4

Related subtypes (11): tooth agenesis, selective, 1, tooth agenesis, selective, X-linked, 1, tooth agenesis, selective, 2, 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

501 retrieved; paginated sample, class counts are floors:

267 likely benign, 90 uncertain significance, 60 pathogenic, 37 conflicting classifications of pathogenicity, 26 pathogenic/likely pathogenic, 14 likely pathogenic, 4 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
464177	NC_000002.12:g.(?218880976)(218893291_?)del	LOC129935621	Pathogenic	criteria provided, single submitter
1070433	NM_025216.3(WNT10A):c.648del (p.Asp217fs)	WNT10A	Pathogenic	criteria provided, single submitter
1070444	NM_025216.3(WNT10A):c.295del (p.Gln99fs)	WNT10A	Pathogenic	criteria provided, single submitter
1072161	NM_025216.3(WNT10A):c.990_1003dup (p.Asp335fs)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073272	NM_025216.3(WNT10A):c.495_502dup (p.Glu168fs)	WNT10A	Pathogenic	criteria provided, single submitter
1073385	NM_025216.3(WNT10A):c.932del (p.Glu311fs)	WNT10A	Pathogenic	criteria provided, single submitter
1074378	NM_025216.3(WNT10A):c.832C>T (p.Gln278Ter)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074605	NM_025216.3(WNT10A):c.993del (p.Ser332fs)	WNT10A	Pathogenic	criteria provided, single submitter
1075184	NM_025216.3(WNT10A):c.315G>A (p.Trp105Ter)	WNT10A	Pathogenic	criteria provided, single submitter
1075261	NM_025216.3(WNT10A):c.490C>T (p.Arg164Ter)	WNT10A	Pathogenic	criteria provided, single submitter
1075424	NM_025216.3(WNT10A):c.932dup (p.Pro312fs)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075575	NM_025216.3(WNT10A):c.847_851del (p.Phe283fs)	WNT10A	Pathogenic	criteria provided, single submitter
1076644	NM_025216.3(WNT10A):c.55_56dup (p.Pro20fs)	WNT10A	Pathogenic	criteria provided, single submitter
1365136	NM_025216.3(WNT10A):c.532_536del (p.Gln178fs)	WNT10A	Pathogenic	criteria provided, single submitter
1404347	NM_025216.3(WNT10A):c.85del (p.Leu29fs)	WNT10A	Pathogenic	criteria provided, single submitter
1412867	NM_025216.3(WNT10A):c.1091dup (p.Ser365fs)	WNT10A	Pathogenic	criteria provided, single submitter
1417009	NM_025216.3(WNT10A):c.580del (p.Glu194fs)	WNT10A	Pathogenic	criteria provided, single submitter
1453389	NM_025216.3(WNT10A):c.354T>A (p.Tyr118Ter)	WNT10A	Pathogenic	criteria provided, single submitter
1453576	NM_025216.3(WNT10A):c.627G>A (p.Trp209Ter)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458073	NM_025216.3(WNT10A):c.1063del (p.Ala355fs)	WNT10A	Pathogenic	criteria provided, single submitter
1460070	NC_000002.11:g.(?219745718)(219757993_?)del	WNT10A	Pathogenic	criteria provided, single submitter
1466056	NM_025216.3(WNT10A):c.1A>T (p.Met1Leu)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1484123	NM_025216.3(WNT10A):c.322T>C (p.Ser108Pro)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1904869	NM_025216.3(WNT10A):c.3G>A (p.Met1Ile)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1916936	NM_025216.3(WNT10A):c.37C>T (p.Arg13Ter)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2026165	NM_025216.3(WNT10A):c.68G>A (p.Trp23Ter)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2030181	NM_025216.3(WNT10A):c.574del (p.Val192fs)	WNT10A	Pathogenic	criteria provided, single submitter
2030582	NM_025216.3(WNT10A):c.1046del (p.Glu349fs)	WNT10A	Pathogenic	criteria provided, single submitter
2034704	NM_025216.3(WNT10A):c.673del (p.Ser225fs)	WNT10A	Pathogenic	criteria provided, single submitter
2076317	NM_025216.3(WNT10A):c.983_984del (p.Arg328fs)	WNT10A	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
WNT10A	Strong	Autosomal dominant	tooth agenesis, selective, 4	10

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

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
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	gencc,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.

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)
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS

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
bone marrow cell	1
lower esophagus mucosa	1
primordial germ cell in gonad	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT10A	1,092

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT10A	Q9GZT5	82.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
WNT ligand biogenesis and trafficking	1	423.0×	0.005	WNT10A
Class B/2 (Secretin family receptors)	1	190.3×	0.005	WNT10A

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
epidermis morphogenesis	1	2808.7×	0.002	WNT10A
regulation of odontogenesis of dentin-containing tooth	1	2407.4×	0.002	WNT10A
tongue development	1	2106.5×	0.002	WNT10A
sebaceous gland development	1	2106.5×	0.002	WNT10A
neural crest cell differentiation	1	1532.0×	0.002	WNT10A
odontogenesis	1	526.6×	0.004	WNT10A
hair follicle morphogenesis	1	495.6×	0.004	WNT10A
skin development	1	443.5×	0.004	WNT10A
hair follicle development	1	383.0×	0.004	WNT10A
cell fate commitment	1	295.6×	0.005	WNT10A
cellular response to transforming growth factor beta stimulus	1	276.3×	0.005	WNT10A
canonical Wnt signaling pathway	1	153.2×	0.008	WNT10A
neuron differentiation	1	100.3×	0.011	WNT10A
positive regulation of gene expression	1	38.7×	0.026	WNT10A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	WNT10A

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)
WNT10A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.