Tooth agenesis, selective, 1

Summary

Tooth agenesis, selective, 1 (MONDO:0007129) is a disease caused by MSX1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: MSX1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, 1
Mondo ID	MONDO:0007129
OMIM	106600
UMLS	C3489529
MedGen	483482
GARD	0018244
Is cancer (heuristic)	no

Also known as: MSX1 tooth agenesis · MSX1-related tooth agenesis with or without orofacial cleft · STHAG1 · tooth agenesis caused by mutation in MSX1 · tooth agenesis, selective, 1 · tooth agenesis, selective, 1, with or without orofacial cleft · tooth agenesis, selective, type 1

Data availability: 20 ClinVar variants · 2 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, 1

Related subtypes (11): tooth agenesis, selective, 4, 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

20 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 conflicting classifications of pathogenicity, 3 uncertain significance, 2 likely pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14880	NM_002448.3(MSX1):c.332C>A (p.Ser111Ter)	LOC129992137	Pathogenic	no assertion criteria provided
14886	NM_002448.3(MSX1):c.200T>A (p.Met67Lys)	LOC129992137	Pathogenic	no assertion criteria provided
4711875	NM_002448.3(MSX1):c.275C>A (p.Ser92Ter)	LOC129992137	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127273	NM_002448.3(MSX1):c.910_911dup (p.Ter304TyrextTer?)	MSX1	Pathogenic	no assertion criteria provided
14879	NM_002448.3(MSX1):c.605G>C (p.Arg202Pro)	MSX1	Pathogenic	no assertion criteria provided
14881	NM_002448.3(MSX1):c.577C>T (p.Gln193Ter)	MSX1	Pathogenic	no assertion criteria provided
14887	NM_002448.3(MSX1):c.81dup (p.Gly28fs)	MSX1	Pathogenic	no assertion criteria provided
3242443	NM_002448.3(MSX1):c.739C>T (p.Pro247Ser)	MSX1	Pathogenic	criteria provided, single submitter
3242444	NM_002448.3(MSX1):c.466_469+1del	MSX1	Pathogenic	criteria provided, single submitter
1708558	NM_001204.7(BMPR2):c.1429A>G (p.Lys477Glu)	BMPR2	Likely pathogenic	criteria provided, single submitter
4820125	NM_002448.3(MSX1):c.469+1G>T	MSX1	Likely pathogenic	criteria provided, single submitter
1023306	NM_004655.4(AXIN2):c.1060-3T>C	AXIN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408793	NM_004655.4(AXIN2):c.2078C>T (p.Thr693Met)	AXIN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2078308	NM_002448.3(MSX1):c.655T>C (p.Trp219Arg)	MSX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225414	NM_002448.3(MSX1):c.471G>T (p.Arg157Ser)	MSX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2664032	NM_002448.3(MSX1):c.641C>T (p.Thr214Met)	MSX1	Uncertain significance	no assertion criteria provided
3067988	NM_002448.3(MSX1):c.697G>C (p.Ala233Pro)	MSX1	Uncertain significance	criteria provided, single submitter
835937	NM_002448.3(MSX1):c.682_683del (p.Lys228fs)	MSX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
333642	NM_001204.7(BMPR2):c.1042G>A (p.Val348Ile)	BMPR2	Likely benign	reviewed by expert panel
703022	NM_002448.3(MSX1):c.218C>T (p.Pro73Leu)	LOC129992137	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 9 · 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
MSX1	Strong	Autosomal dominant	tooth agenesis, selective, 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSX1	Orphanet:141291	Cleft lip and alveolus
MSX1	Orphanet:199302	Isolated cleft lip
MSX1	Orphanet:199306	Cleft lip/palate
MSX1	Orphanet:2228	Hypodontia-dysplasia of nails syndrome
MSX1	Orphanet:99798	Oligodontia
BMPR2	Orphanet:275777	Heritable pulmonary arterial hypertension
BMPR2	Orphanet:275786	Drug- or toxin-induced pulmonary arterial hypertension
BMPR2	Orphanet:31837	Pulmonary venoocclusive disease
AXIN2	Orphanet:401911	AXIN2-related polyposis

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
MSX1	HGNC:7391	ENSG00000163132	P28360	Homeobox protein MSX-1	gencc,clinvar
BMPR2	HGNC:1078	ENSG00000204217	Q13873	Bone morphogenetic protein receptor type-2	clinvar
AXIN2	HGNC:904	ENSG00000168646	Q9Y2T1	Axin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSX1	Homeobox protein MSX-1	Acts as a transcriptional repressor.
BMPR2	Bone morphogenetic protein receptor type-2	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
AXIN2	Axin-2	Inhibitor of the Wnt signaling pathway.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.313
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MSX1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
BMPR2	Kinase	yes		TGFB_receptor, Activin_recp, Prot_kinase_dom
AXIN2	Other/Unknown	no		DIX, Axin_b-cat-bd, RGS

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
buccal mucosa cell	1
choroid plexus epithelium	1
endocervix	1
lower lobe of lung	1
tendon of biceps brachii	1
visceral pleura	1
body of uterus	1
oviduct epithelium	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSX1	222	ubiquitous	marker	buccal mucosa cell, choroid plexus epithelium, endocervix
BMPR2	271	ubiquitous	marker	visceral pleura, lower lobe of lung, tendon of biceps brachii
AXIN2	221	ubiquitous	marker	oviduct epithelium, upper arm skin, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMPR2	3,152
AXIN2	3,049
MSX1	2,261

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMPR2	Q13873	7
AXIN2	Q9Y2T1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MSX1	P28360	66.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	380.7×	0.028	AXIN2
Repression of WNT target genes	1	237.9×	0.028	AXIN2
Specification of the neural plate border	1	211.5×	0.028	MSX1
Signaling by BMP	1	119.0×	0.035	BMPR2
Gastrulation	1	86.5×	0.035	MSX1
Degradation of AXIN	1	82.8×	0.035	AXIN2
Ca2+ pathway	1	59.5×	0.035	AXIN2
CHD6, CHD7, CHD8, CHD9 subfamily	1	49.4×	0.035	AXIN2
Deubiquitination	1	41.4×	0.035	AXIN2
Formation of the beta-catenin:TCF transactivating complex	1	40.1×	0.035	AXIN2
TCF dependent signaling in response to WNT	1	39.2×	0.035	AXIN2
Signaling by TGFB family members	1	38.5×	0.035	BMPR2
Signaling by WNT	1	37.3×	0.035	AXIN2
Signal Transduction	2	6.8×	0.035	BMPR2, AXIN2
Ub-specific processing proteases	1	17.7×	0.067	AXIN2
Post-translational protein modification	1	6.4×	0.167	AXIN2
Developmental Biology	1	4.8×	0.205	MSX1
Metabolism of proteins	1	4.1×	0.223	AXIN2

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
mitral valve morphogenesis	2	1123.5×	1e-04	BMPR2, AXIN2
stem cell differentiation	2	200.6×	0.002	MSX1, BMPR2
regulation of mismatch repair	1	5617.3×	0.002	AXIN2
regulation of chondrocyte development	1	5617.3×	0.002	AXIN2
negative regulation of odontoblast differentiation	1	5617.3×	0.002	MSX1
semi-lunar valve development	1	5617.3×	0.002	BMPR2
BMP signaling pathway	2	133.8×	0.002	MSX1, BMPR2
anterior/posterior pattern specification	2	120.8×	0.002	MSX1, BMPR2
negative regulation of cell growth	2	96.0×	0.002	MSX1, BMPR2
osteoblast differentiation	2	80.8×	0.003	BMPR2, AXIN2
obsolete negative regulation of cell proliferation involved in heart valve morphogenesis	1	2808.7×	0.003	BMPR2
regulation of lung blood pressure	1	2808.7×	0.003	BMPR2
cell surface receptor signaling pathway involved in heart development	1	2808.7×	0.003	MSX1
regulation of centromeric sister chromatid cohesion	1	1872.4×	0.004	AXIN2
positive regulation of mesenchymal cell apoptotic process	1	1872.4×	0.004	MSX1
pulmonary valve development	1	1404.3×	0.004	BMPR2
negative regulation of striated muscle cell differentiation	1	1404.3×	0.004	MSX1
endochondral bone morphogenesis	1	1404.3×	0.004	BMPR2
activation of meiosis	1	1404.3×	0.004	MSX1
negative regulation of chondrocyte proliferation	1	1404.3×	0.004	BMPR2
aortic valve development	1	1123.5×	0.004	BMPR2
tricuspid valve morphogenesis	1	1123.5×	0.004	BMPR2
embryonic nail plate morphogenesis	1	1123.5×	0.004	MSX1
regulation of odontogenesis	1	1123.5×	0.004	MSX1
positive regulation of odontogenesis	1	1123.5×	0.004	MSX1
maintenance of DNA repeat elements	1	1123.5×	0.004	AXIN2
cartilage morphogenesis	1	1123.5×	0.004	MSX1
venous blood vessel development	1	1123.5×	0.004	BMPR2
intramembranous ossification	1	936.2×	0.004	AXIN2
chondrocyte differentiation involved in endochondral bone morphogenesis	1	936.2×	0.004	AXIN2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BMPR2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR2	19	4
MSX1	0	0
AXIN2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	BMPR2
RUXOLITINIB	4	BMPR2
BOSUTINIB	4	BMPR2
DEUCRAVACITINIB	4	BMPR2
NINTEDANIB	4	BMPR2
SUNITINIB	4	BMPR2
LINIFANIB	3	BMPR2
ORANTINIB	3	BMPR2
DOVITINIB	3	BMPR2
LESTAURTINIB	3	BMPR2
SILMITASERTIB	2	BMPR2
SU-014813	2	BMPR2
OSI-027	2	BMPR2
AT-9283	2	BMPR2
TOZASERTIB	2	BMPR2
KW-2449	1	BMPR2
RGB-286638	1	BMPR2
PF-03814735	1	BMPR2
CYC-116	1	BMPR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BMPR2	166	Binding:165, ADMET:1
AXIN2	14	Binding:14

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BMPR2	166

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

19 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	BMPR2
RUXOLITINIB	4	BMPR2
BOSUTINIB	4	BMPR2
DEUCRAVACITINIB	4	BMPR2
NINTEDANIB	4	BMPR2
SUNITINIB	4	BMPR2
LINIFANIB	3	BMPR2
ORANTINIB	3	BMPR2
DOVITINIB	3	BMPR2
LESTAURTINIB	3	BMPR2
SILMITASERTIB	2	BMPR2
SU-014813	2	BMPR2
OSI-027	2	BMPR2
AT-9283	2	BMPR2
TOZASERTIB	2	BMPR2
KW-2449	1	BMPR2
RGB-286638	1	BMPR2
PF-03814735	1	BMPR2
CYC-116	1	BMPR2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BMPR2
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	2	MSX1, AXIN2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MSX1	0	—
AXIN2	14	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.