Tooth agenesis, selective, 3

Summary

Tooth agenesis, selective, 3 (MONDO:0011477) is a disease caused by PAX9 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PAX9 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 91

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, 3
Mondo ID	MONDO:0011477
MeSH	C567036
OMIM	604625
UMLS	C1970291
MedGen	410035
GARD	0018247
Is cancer (heuristic)	no

Also known as: hypodontia/oligodontia 3 · PAX9 tooth agenesis · PAX9-related selective tooth agenesis · STHAG3 · tooth agenesis caused by mutation in PAX9 · tooth agenesis, selective, 3 · tooth agenesis, selective, type 3

Data availability: 91 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › tooth agenesis › tooth agenesis, selective, 3

Related subtypes (11): tooth agenesis, selective, 1, tooth agenesis, selective, 4, tooth agenesis, selective, X-linked, 1, tooth agenesis, selective, 2, 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

91 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 19 pathogenic, 11 likely pathogenic, 9 benign, 4 likely benign, 4 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13769	NC_000014.9:g.(36613381_36657568)(36679362?)del	LOC108281111	Pathogenic	no assertion criteria provided
13767	NM_001372076.1(PAX9):c.218dup (p.Ser74fs)	PAX9	Pathogenic	no assertion criteria provided
13768	NM_001372076.1(PAX9):c.340A>T (p.Lys114Ter)	PAX9	Pathogenic	no assertion criteria provided
13771	NM_001372076.1(PAX9):c.62T>C (p.Leu21Pro)	PAX9	Pathogenic	no assertion criteria provided
13772	NM_001372076.1(PAX9):c.176_182delinsAGCCACACAGTCTTGCCACACACAGTCTTCTGCCTCATCTCAAACTACCAGACCCATAACATCCCCCCATCCCAACACATGGTTCGCATTTTCCACCTCCCCCGCCTCTCGCGCCGAGGCAGCCTCAGCCCGGCTTGCTCACTTGGAGAGTGCGGCCGGGGCTGGACTTGGGGCGCAGCCCGGGAGGCCCGAGCCTGCTTGGGGCTGCCGGCTGCAGACTCCGCTGTGGGCAGAGCAGCTTGCTTGGGGACTACTACGGCCGGGATCGGTAATCAGGCCAAGAT (p.Arg59_Asn61delinsGlnProHisSerLeuAlaThrHisSerLeuLeuProHisLeuLysLeuProAspProTer)	PAX9	Pathogenic	no assertion criteria provided
13773	NM_001372076.1(PAX9):c.83G>C (p.Arg28Pro)	PAX9	Pathogenic	no assertion criteria provided
13774	NM_001372076.1(PAX9):c.76C>T (p.Arg26Trp)	PAX9	Pathogenic	criteria provided, single submitter
13776	NM_001372076.1(PAX9):c.792_793insC (p.Val265fs)	PAX9	Pathogenic	no assertion criteria provided
13777	NM_001372076.1(PAX9):c.1A>G (p.Met1Val)	PAX9	Pathogenic	no assertion criteria provided
13778	NM_001372076.1(PAX9):c.619_621delinsTACCGACCAAGGTAGGGCATCCCT (p.Ile207delinsTyrArgProArgTer)	PAX9	Pathogenic	no assertion criteria provided
13780	PAX9, 1-BP INS, 190G	PAX9	Pathogenic	no assertion criteria provided
13781	NM_001372076.1(PAX9):c.139C>T (p.Arg47Trp)	PAX9	Pathogenic	no assertion criteria provided
155939	NM_001372076.1(PAX9):c.336C>G (p.Cys112Trp)	PAX9	Pathogenic	no assertion criteria provided
1693560	NM_001372076.1(PAX9):c.354del (p.Ser119fs)	PAX9	Pathogenic	criteria provided, single submitter
1693561	NM_001372076.1(PAX9):c.648dup (p.Tyr217fs)	PAX9	Pathogenic	criteria provided, multiple submitters, no conflicts
1693562	NM_001372076.1(PAX9):c.191G>T (p.Gly64Val)	PAX9	Pathogenic	criteria provided, single submitter
2577026	NM_001372076.1(PAX9):c.112C>T (p.Arg38Ter)	PAX9	Pathogenic	criteria provided, single submitter
375454	NM_001372076.1(PAX9):c.59C>T (p.Pro20Leu)	PAX9	Pathogenic	criteria provided, single submitter
430692	NC_000014.9:g.36662092G>A	PAX9	Pathogenic	no assertion criteria provided
13770	NM_001372076.1(PAX9):c.271A>G (p.Lys91Glu)	PAX9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1697312	NM_001372076.1(PAX9):c.487_490dup (p.Ser164fs)	PAX9	Likely pathogenic	criteria provided, single submitter
2577025	NM_001372076.1(PAX9):c.133_136del (p.Gln45fs)	PAX9	Likely pathogenic	no assertion criteria provided
2577030	NM_001372076.1(PAX9):c.191del (p.Gly64fs)	PAX9	Likely pathogenic	no assertion criteria provided
2577031	NM_001372076.1(PAX9):c.305del (p.Ile102fs)	PAX9	Likely pathogenic	no assertion criteria provided
2577032	NM_001372076.1(PAX9):c.365C>A (p.Ser122Tyr)	PAX9	Likely pathogenic	no assertion criteria provided
2577033	NM_001372076.1(PAX9):c.395del (p.Gly132fs)	PAX9	Likely pathogenic	no assertion criteria provided
3254837	NM_001372076.1(PAX9):c.356C>T (p.Ser119Phe)	PAX9	Likely pathogenic	criteria provided, single submitter
3381209	NM_001372076.1(PAX9):c.670G>T (p.Glu224Ter)	PAX9	Likely pathogenic	criteria provided, single submitter
666317	NM_001372076.1(PAX9):c.51C>G (p.Asn17Lys)	PAX9	Likely pathogenic	criteria provided, single submitter
975792	NM_001372076.1(PAX9):c.230G>A (p.Arg77Gln)	PAX9	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PAX9	Definitive	Autosomal dominant	tooth agenesis, selective, 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX9	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
PAX9	HGNC:8623	ENSG00000198807	P55771	Paired box protein Pax-9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX9	Paired box protein Pax-9	Transcription factor required for normal development of thymus, parathyroid glands, ultimobranchial bodies, teeth, skeletal elements of skull and larynx as well as distal limbs.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX9	Transcription factor	no		Paired_dom, Homeodomain-like_sf, WH-like_DNA-bd_sf

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
esophagus mucosa	1
lower esophagus mucosa	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX9	128	broad	marker	lower esophagus mucosa, parotid gland, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX9	1,383

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAX9	P55771	64.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
regulation of odontogenesis	1	3370.4×	0.002	PAX9
endoderm development	1	624.1×	0.004	PAX9
odontogenesis	1	526.6×	0.004	PAX9
face morphogenesis	1	495.6×	0.004	PAX9
cellular response to growth factor stimulus	1	318.0×	0.004	PAX9
negative regulation of DNA-templated transcription	1	31.6×	0.037	PAX9
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PAX9

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
PAX9	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	PAX9

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)
PAX9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.