Odontochondrodysplasia 1

Summary

Odontochondrodysplasia 1 (MONDO:0100325) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 33
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000703	Dentinogenesis imperfecta	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000926	Platyspondyly	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0004279	Short palm	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0010579	Cone-shaped epiphysis	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0000684	Delayed eruption of teeth	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002673	Coxa valga	Frequent (30-79%)
HP:0003278	Square pelvis	Frequent (30-79%)
HP:0000278	Retrognathia	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0001522	Death in infancy	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)
HP:0006487	Bowing of the long bones	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	odontochondrodysplasia 1
Mondo ID	MONDO:0100325
OMIM	184260
Orphanet	166272
SNOMED CT	717823001
UMLS	C5542277
MedGen	1784281
GARD	0008717
Is cancer (heuristic)	no

Also known as: chondrodysplasia-dentinogenesis imperfecta-joint laxity syndrome · Goldblatt chondrodysplasia · Goldblatt syndrome · ODCD · odontochondrodysplasia

Data availability: 33 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › spondylometaphyseal dysplasia › odontochondrodysplasia › odontochondrodysplasia 1

Related subtypes (1): odontochondrodysplasia 2 with hearing loss and diabetes

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

33 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 9 pathogenic, 7 likely pathogenic, 3 benign, 2 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
522812	NM_004239.4(TRIP11):c.2038G>T (p.Glu680Ter)	TRIP11	Pathogenic	criteria provided, single submitter
522813	NM_004239.4(TRIP11):c.4557+1G>T	TRIP11	Pathogenic	criteria provided, single submitter
546569	NM_004239.4(TRIP11):c.2467_2470del (p.Arg823fs)	TRIP11	Pathogenic	criteria provided, multiple submitters, no conflicts
5508	NM_004239.4(TRIP11):c.790C>T (p.Arg264Ter)	TRIP11	Pathogenic	criteria provided, multiple submitters, no conflicts
619107	NM_004239.4(TRIP11):c.586C>T (p.Gln196Ter)	TRIP11	Pathogenic	criteria provided, single submitter
619108	NM_004239.4(TRIP11):c.2993_2994del (p.Lys998fs)	TRIP11	Pathogenic	no assertion criteria provided
619111	NM_004239.4(TRIP11):c.4815_4818del (p.Glu1606fs)	TRIP11	Pathogenic	no assertion criteria provided
619113	NM_004239.4(TRIP11):c.2128_2129del (p.Ile710fs)	TRIP11	Pathogenic	no assertion criteria provided
619114	NM_004239.4(TRIP11):c.1622del (p.Lys541fs)	TRIP11	Pathogenic	no assertion criteria provided
1251990	NM_004239.4(TRIP11):c.5420G>T (p.Gly1807Val)	TRIP11	Likely pathogenic	criteria provided, single submitter
4277865	NM_004239.4(TRIP11):c.5160+1G>T	TRIP11	Likely pathogenic	criteria provided, single submitter
4845674	NM_004239.4(TRIP11):c.2920C>T (p.Gln974Ter)	TRIP11	Likely pathogenic	criteria provided, single submitter
4845721	NM_004239.4(TRIP11):c.3128_3131del (p.Thr1043fs)	TRIP11	Likely pathogenic	criteria provided, single submitter
619109	NM_004239.4(TRIP11):c.4534C>T (p.Gln1512Ter)	TRIP11	Likely pathogenic	criteria provided, single submitter
619110	NM_004239.4(TRIP11):c.1228G>T (p.Asp410Tyr)	TRIP11	Likely pathogenic	criteria provided, single submitter
619112	NM_004239.4(TRIP11):c.5416A>G (p.Met1806Val)	TRIP11	Likely pathogenic	criteria provided, single submitter
314961	NM_004239.4(TRIP11):c.2357A>C (p.Asp786Ala)	TRIP11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885425	NM_004239.4(TRIP11):c.4062A>C (p.Lys1354Asn)	TRIP11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1062975	NM_004239.4(TRIP11):c.3215A>G (p.His1072Arg)	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1504467	NM_004239.4(TRIP11):c.4447C>A (p.Gln1483Lys)	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
2162835	NM_004239.4(TRIP11):c.4754G>A (p.Arg1585His)	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
2504576	NM_004239.4(TRIP11):c.5343-314T>C	TRIP11	Uncertain significance	criteria provided, single submitter
3065105	NM_004239.4(TRIP11):c.4894C>T (p.His1632Tyr)	TRIP11	Uncertain significance	criteria provided, single submitter
314969	NM_004239.4(TRIP11):c.1289A>G (p.Glu430Gly)	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
314991	NM_004239.4(TRIP11):c.-333G>A	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892725	NM_004239.4(TRIP11):c.31G>A (p.Gly11Arg)	TRIP11	Uncertain significance	criteria provided, single submitter
499894	NM_004239.4(TRIP11):c.4712G>A (p.Arg1571His)	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
959981	NM_004239.4(TRIP11):c.4726C>T (p.Arg1576Cys)	TRIP11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1178934	NM_004239.4(TRIP11):c.5260+24T>C	TRIP11	Benign	criteria provided, multiple submitters, no conflicts
1261817	NM_004239.4(TRIP11):c.1527+41A>G	TRIP11	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRIP11	Orphanet:166272	Odontochondrodysplasia
TRIP11	Orphanet:93299	Achondrogenesis type 1A

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
TRIP11	HGNC:12305	ENSG00000100815	Q15643	Thyroid receptor-interacting protein 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIP11	Thyroid receptor-interacting protein 11	Is a membrane tether required for vesicle tethering to Golgi.

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)
TRIP11	Other/Unknown	no		GRIP_dom

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
adrenal tissue	1
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIP11	270	ubiquitous	marker	calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIP11	2,991

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRIP11	Q15643	66.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Signaling by FLT3 fusion proteins	1	571.0×	0.005	TRIP11
Intra-Golgi traffic	1	259.6×	0.005	TRIP11
Intraflagellar transport	1	200.3×	0.005	TRIP11

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
obsolete vesicle tethering to Golgi	1	3370.4×	0.002	TRIP11
chondrocyte differentiation involved in endochondral bone morphogenesis	1	2808.7×	0.002	TRIP11
Golgi ribbon formation	1	1532.0×	0.002	TRIP11
protein transmembrane transport	1	1296.3×	0.002	TRIP11
inner ear receptor cell stereocilium organization	1	842.6×	0.002	TRIP11
ventricular septum development	1	495.6×	0.003	TRIP11
cartilage development	1	251.5×	0.006	TRIP11
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.008	TRIP11
Golgi organization	1	133.8×	0.008	TRIP11
transcription by RNA polymerase II	1	70.5×	0.014	TRIP11

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
TRIP11	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	TRIP11

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)
TRIP11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.