Odontochondrodysplasia 2 with hearing loss and diabetes

Summary

Odontochondrodysplasia 2 with hearing loss and diabetes (MONDO:0031010) is a disease caused by MIA3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MIA3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	odontochondrodysplasia 2 with hearing loss and diabetes
Mondo ID	MONDO:0031010
OMIM	619269
UMLS	C5543275
MedGen	1782909
GARD	0025674
Is cancer (heuristic)	no

Also known as: ODCD2 · ondontochondrodysplasia 2 with hearing loss and diabetes

Data availability: 4 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 › skeletal dysplasia › spondylometaphyseal dysplasia › odontochondrodysplasia › odontochondrodysplasia 2 with hearing loss and diabetes

Related subtypes (1): odontochondrodysplasia 1

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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4277882	NM_198551.4(MIA3):c.3720+1G>A	MIA3	Likely pathogenic	criteria provided, single submitter
2584658	NM_198551.4(MIA3):c.3721-9_3721-5del	MIA3	Uncertain significance	criteria provided, single submitter
3065730	NM_198551.4(MIA3):c.5669C>T (p.Pro1890Leu)	MIA3	Uncertain significance	criteria provided, single submitter
3236424	NM_198551.4(MIA3):c.5087G>A (p.Arg1696Gln)	MIA3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
MIA3	Strong	Autosomal recessive	odontochondrodysplasia 2 with hearing loss and diabetes	2

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
MIA3	HGNC:24008	ENSG00000154305	Q5JRA6	Transport and Golgi organization protein 1 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MIA3	Transport and Golgi organization protein 1 homolog	Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MIA3	Scaffold/PPI	no		SH3_domain, SH3-like_dom_sf, cTAGE_MIA/OTOR

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
body of pancreas	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MIA3	282	ubiquitous	marker	calcaneal tendon, adrenal tissue, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MIA3	2,561

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MIA3	Q5JRA6	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Cargo concentration in the ER	1	335.9×	0.023	MIA3
ER to Golgi Anterograde Transport	1	132.8×	0.023	MIA3
Transport to the Golgi and subsequent modification	1	102.9×	0.023	MIA3
Post-translational protein phosphorylation	1	100.2×	0.023	MIA3
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.023	MIA3
Asparagine N-linked glycosylation	1	60.1×	0.028	MIA3
Membrane Trafficking	1	37.1×	0.036	MIA3
Vesicle-mediated transport	1	34.8×	0.036	MIA3
Post-translational protein modification	1	19.2×	0.058	MIA3
Metabolism of proteins	1	12.4×	0.081	MIA3

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
negative regulation of lymphocyte migration	1	3370.4×	0.002	MIA3
negative regulation of leukocyte cell-cell adhesion	1	2808.7×	0.002	MIA3
protein localization to endoplasmic reticulum exit site	1	2106.5×	0.002	MIA3
vesicle cargo loading	1	1404.3×	0.002	MIA3
cellular response to oxidised low-density lipoprotein particle stimulus	1	1404.3×	0.002	MIA3
positive regulation of leukocyte migration	1	991.3×	0.002	MIA3
lipoprotein transport	1	991.3×	0.002	MIA3
COPII-coated vesicle cargo loading	1	991.3×	0.002	MIA3
cell migration involved in sprouting angiogenesis	1	648.1×	0.003	MIA3
endoplasmic reticulum organization	1	421.3×	0.004	MIA3
negative regulation of cell adhesion	1	383.0×	0.004	MIA3
protein secretion	1	263.3×	0.005	MIA3
wound healing	1	227.7×	0.006	MIA3
exocytosis	1	151.8×	0.008	MIA3
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.008	MIA3
negative regulation of cell migration	1	111.6×	0.010	MIA3
protein transport	1	43.9×	0.023	MIA3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MIA3	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
MIA3	1	Binding:1

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	MIA3

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)
MIA3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.