Tooth agenesis, selective, 7

Summary

Tooth agenesis, selective, 7 (MONDO:0014749) is a disease caused by LRP6 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: LRP6 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 39

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, 7
Mondo ID	MONDO:0014749
OMIM	616724
UMLS	C4225231
MedGen	899184
GARD	0018249
Is cancer (heuristic)	no

Also known as: LRP6 tooth agenesis · STHAG7 · tooth agenesis caused by mutation in LRP6 · tooth agenesis, selective, 7 · tooth agenesis, selective, 7; STHAG7 · tooth agenesis, selective, type 7

Data availability: 39 ClinVar variants · 3 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, 7

Related subtypes (11): tooth agenesis, selective, 1, 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, 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

39 retrieved; paginated sample, class counts are floors:

17 pathogenic, 9 uncertain significance, 5 likely pathogenic, 3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1033503	NM_002336.3(LRP6):c.3394_3395del (p.Ser1132fs)	LRP6	Pathogenic	criteria provided, single submitter
1199176	NM_002336.3(LRP6):c.845-1G>A	LRP6	Pathogenic	criteria provided, single submitter
1296979	NM_002336.3(LRP6):c.2840T>C (p.Met947Thr)	LRP6	Pathogenic	no assertion criteria provided
1296980	NM_002336.3(LRP6):c.1154G>C (p.Arg385Pro)	LRP6	Pathogenic	no assertion criteria provided
1328138	NM_002336.3(LRP6):c.56-2A>T	LRP6	Pathogenic	criteria provided, single submitter
1342139	NM_002336.3(LRP6):c.3399del (p.Ala1134fs)	LRP6	Pathogenic	criteria provided, single submitter
1697975	NM_002336.3(LRP6):c.1762+2T>C	LRP6	Pathogenic	no assertion criteria provided
1805121	NM_002336.3(LRP6):c.3332dup (p.Ser1111fs)	LRP6	Pathogenic	criteria provided, single submitter
218878	NM_002336.3(LRP6):c.1779dup (p.Glu594Ter)	LRP6	Pathogenic	no assertion criteria provided
218880	NM_002336.3(LRP6):c.2224_2225dup (p.Leu742fs)	LRP6	Pathogenic	no assertion criteria provided
225148	NM_002336.3(LRP6):c.3398-2A>C	LRP6	Pathogenic	criteria provided, single submitter
2572177	NM_002336.3(LRP6):c.4093G>T (p.Glu1365Ter)	LRP6	Pathogenic	criteria provided, single submitter
2850249	NM_002336.3(LRP6):c.1930C>T (p.Arg644Ter)	LRP6	Pathogenic	criteria provided, multiple submitters, no conflicts
3381211	NM_002336.3(LRP6):c.3074_3082del (p.Ser1025_Tyr1027del)	LRP6	Pathogenic	criteria provided, single submitter
4537441	NM_002336.3(LRP6):c.2292G>A (p.Trp764Ter)	LRP6	Pathogenic	no assertion criteria provided
4537442	NM_002336.3(LRP6):c.1095dup (p.Asp366fs)	LRP6	Pathogenic	no assertion criteria provided
620374	NM_002336.3(LRP6):c.1003C>T (p.Arg335Ter)	LRP6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
689556	NM_002336.3(LRP6):c.2218C>T (p.Gln740Ter)	LRP6	Pathogenic	criteria provided, single submitter
947760	NM_002336.3(LRP6):c.1243C>T (p.Arg415Ter)	LRP6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3341500	NM_001163692.2(UBAP1L):c.910-7G>A	UBAP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2500817	NM_002336.3(LRP6):c.3095G>T (p.Cys1032Phe)	LRP6	Likely pathogenic	criteria provided, single submitter
3900613	NM_002336.3(LRP6):c.1231G>T (p.Asp411Tyr)	LRP6	Likely pathogenic	criteria provided, single submitter
4081498	NM_002336.3(LRP6):c.875del (p.Gly292fs)	LRP6	Likely pathogenic	criteria provided, single submitter
4755459	NM_002336.3(LRP6):c.3550C>T (p.Arg1184Ter)	LRP6	Likely pathogenic	criteria provided, single submitter
4819725	NM_002336.3(LRP6):c.400dup (p.Trp134fs)	LRP6	Likely pathogenic	criteria provided, single submitter
225150	NM_002336.3(LRP6):c.1406C>T (p.Pro469Leu)	LRP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2464538	NM_002336.3(LRP6):c.4525C>T (p.Pro1509Ser)	LRP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
732299	NM_002336.3(LRP6):c.752A>G (p.Asn251Ser)	LRP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1255586	NM_002336.3(LRP6):c.3406C>T (p.Arg1136Trp)	LRP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2056656	NM_002336.3(LRP6):c.3107A>G (p.Asn1036Ser)	LRP6	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
LRP6	Definitive	Autosomal dominant	tooth agenesis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP6	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
LRP6	Orphanet:99798	Oligodontia
UBAP1L	Orphanet:1872	Cone rod dystrophy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRP6	HGNC:6698	ENSG00000070018	O75581	Low-density lipoprotein receptor-related protein 6	gencc,clinvar
UBAP1L	HGNC:40028	ENSG00000246922	F5GYI3	Ubiquitin-associated protein 1-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP6	Low-density lipoprotein receptor-related protein 6	Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRP6	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
UBAP1L	Other/Unknown	no		UMA, UBAP1, UBAP1_C

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
corpus callosum	1
ventricular zone	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP6	139	ubiquitous	marker	calcaneal tendon, corpus callosum, ventricular zone
UBAP1L	171	tissue_specific	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP6	2,525
UBAP1L	164

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP6	O75581	30

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UBAP1L	F5GYI3	66.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 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
Signaling by RNF43 mutants	1	1268.9×	0.005	LRP6
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	713.8×	0.005	LRP6
Signaling by WNT in cancer	1	601.0×	0.005	LRP6
Regulation of FZD by ubiquitination	1	519.1×	0.005	LRP6
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.006	LRP6
TCF dependent signaling in response to WNT	1	117.7×	0.013	LRP6
Signaling by WNT	1	112.0×	0.013	LRP6
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.022	LRP6
Disease	1	13.1×	0.085	LRP6
Signal Transduction	1	10.2×	0.098	LRP6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neural crest formation	1	936.2×	0.008	LRP6
neural crest cell differentiation	1	766.0×	0.008	LRP6
negative regulation of smooth muscle cell apoptotic process	1	702.2×	0.008	LRP6
midbrain dopaminergic neuron differentiation	1	601.9×	0.008	LRP6
cellular response to cholesterol	1	421.3×	0.009	LRP6
dopaminergic neuron differentiation	1	312.1×	0.010	LRP6
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	1	271.8×	0.010	UBAP1L
positive regulation of cell cycle	1	221.7×	0.011	LRP6
response to peptide hormone	1	195.9×	0.011	LRP6
canonical Wnt signaling pathway	1	76.6×	0.025	LRP6
positive regulation of cytosolic calcium ion concentration	1	58.5×	0.026	LRP6
protein localization to plasma membrane	1	54.4×	0.026	LRP6
cell-cell adhesion	1	50.8×	0.026	LRP6
Wnt signaling pathway	1	49.9×	0.026	LRP6
endocytosis	1	47.6×	0.026	LRP6
chemical synaptic transmission	1	38.6×	0.031	LRP6
nervous system development	1	23.0×	0.048	LRP6
positive regulation of DNA-templated transcription	1	14.0×	0.074	LRP6
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	LRP6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRP6	0	0
UBAP1L	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
LRP6	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	LRP6, UBAP1L

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)
LRP6	9	—
UBAP1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.