Tooth agenesis, selective, 10

Summary

Tooth agenesis, selective, 10 (MONDO:0859339) is a disease caused by TSPEAR (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TSPEAR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, 10
Mondo ID	MONDO:0859339
OMIM	620173
UMLS	C5774277
MedGen	1824050
GARD	0026706
Is cancer (heuristic)	no

Data availability: 25 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, 10

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, 7, tooth agenesis, selective, 8, tooth agenesis, selective, 9, hypodontia/oligodontia with orofacial cleft, tooth agenesis, selective, with orofacial cleft

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

25 retrieved; paginated sample, class counts are floors:

11 pathogenic, 7 conflicting classifications of pathogenicity, 5 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1806397	NM_144991.3(TSPEAR):c.1663C>T (p.Gln555Ter)	LOC126653398	Pathogenic	no assertion criteria provided
37311	NM_144991.3(TSPEAR):c.1728del (p.Lys577fs)	LOC126653398	Pathogenic	criteria provided, single submitter
1030229	NM_144991.3(TSPEAR):c.789T>G (p.Tyr263Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
1311928	NM_144991.3(TSPEAR):c.430C>T (p.Arg144Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
1705559	NM_144991.3(TSPEAR):c.1785AGA[1] (p.Glu596del)	TSPEAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1806398	NM_144991.3(TSPEAR):c.1899dup (p.Thr634fs)	TSPEAR	Pathogenic	no assertion criteria provided
2081026	NM_144991.3(TSPEAR):c.1093C>T (p.Gln365Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2891535	NM_144991.3(TSPEAR):c.2T>C (p.Met1Thr)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
2986614	NM_144991.3(TSPEAR):c.1463C>A (p.Ser488Ter)	TSPEAR	Pathogenic	criteria provided, multiple submitters, no conflicts
4081842	NM_144991.3(TSPEAR):c.1238_1239del (p.Phe413fs)	TSPEAR	Pathogenic	criteria provided, single submitter
4081843	NM_144991.3(TSPEAR):c.1794T>A (p.Tyr598Ter)	TSPEAR	Pathogenic	criteria provided, single submitter
4526656	NM_144991.3(TSPEAR):c.1438del (p.Glu480fs)	TSPEAR	Pathogenic	criteria provided, single submitter
1806394	NM_144991.3(TSPEAR):c.1505del (p.Lys502fs)	TSPEAR	Likely pathogenic	criteria provided, single submitter
1188184	NM_144991.3(TSPEAR):c.1493_1494delinsTG (p.Gly498Val)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197259	NM_144991.3(TSPEAR):c.1877T>C (p.Phe626Ser)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1203962	NM_144991.3(TSPEAR):c.1918T>C (p.Trp640Arg)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227135	NM_144991.3(TSPEAR):c.1915G>A (p.Asp639Asn)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
493326	NM_144991.3(TSPEAR):c.1870G>T (p.Glu624Ter)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
504870	NM_144991.3(TSPEAR):c.1528C>T (p.Arg510Ter)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
805690	NM_144991.3(TSPEAR):c.1330C>T (p.Arg444Trp)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3065447	NM_144991.3(TSPEAR):c.1726_1728del (p.Val576del)	LOC126653398	Uncertain significance	criteria provided, single submitter
1806395	NM_144991.3(TSPEAR):c.1331G>A (p.Arg444Gln)	TSPEAR	Uncertain significance	criteria provided, single submitter
3587696	NM_144991.3(TSPEAR):c.1882G>A (p.Ala628Thr)	TSPEAR	Uncertain significance	criteria provided, single submitter
3780755	NM_144991.3(TSPEAR):c.1336+5G>A	TSPEAR	Uncertain significance	criteria provided, single submitter
4081844	NM_144991.3(TSPEAR):c.1919G>A (p.Trp640Ter)	TSPEAR	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
TSPEAR	Strong	Autosomal recessive	ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSPEAR	Orphanet:685067	Hypodontia-scalp hypotrichosis-facial dysmorphism syndrome

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
TSPEAR	HGNC:1268	ENSG00000175894	Q8WU66	Thrombospondin-type laminin G domain and EAR repeat-containing protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSPEAR	Thrombospondin-type laminin G domain and EAR repeat-containing protein	Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

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)
TSPEAR	Other/Unknown	no		EPTP, EAR, ConA-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
adenohypophysis	1
pituitary gland	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSPEAR	88	tissue_specific	yes	primordial germ cell in gonad, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSPEAR	839

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPEAR	Q8WU66	87.47

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
tooth mineralization	1	5617.3×	0.001	TSPEAR
hair cycle process	1	2808.7×	0.001	TSPEAR
regulation of Notch signaling pathway	1	842.6×	0.002	TSPEAR
Notch signaling pathway	1	141.6×	0.011	TSPEAR
sensory perception of sound	1	100.9×	0.012	TSPEAR
signal transduction	1	16.1×	0.062	TSPEAR

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
TSPEAR	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	TSPEAR

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)
TSPEAR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.