Epiphyseal dysplasia, multiple, 3

Summary

Epiphyseal dysplasia, multiple, 3 (MONDO:0010964) is a disease caused by COL9A3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COL9A3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 57

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epiphyseal dysplasia, multiple, 3
Mondo ID	MONDO:0010964
MeSH	C535503
OMIM	600969
DOID	DOID:0070304
UMLS	C1832998
MedGen	322091
GARD	0009792
Is cancer (heuristic)	no

Also known as: COL9A3 multiple epiphyseal dysplasia (disease) · EDM3 · epiphyseal dysplasia multiple 3 · epiphyseal dysplasia, multiple, 3 · epiphyseal dysplasia, multiple, 3, with or without myopathy · epiphyseal dysplasia, multiple, type 3 · multiple epiphyseal dysplasia (disease) caused by mutation in COL9A3 · multiple epiphyseal dysplasia 3

Data availability: 57 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › collagenopathy › multiple epiphyseal dysplasia due to collagen 9 anomaly › epiphyseal dysplasia, multiple, 3

Related subtypes (2): epiphyseal dysplasia, multiple, 2, epiphyseal dysplasia, multiple, 6

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

57 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 7 benign, 5 conflicting classifications of pathogenicity, 5 pathogenic, 4 likely pathogenic, 4 benign/likely benign, 3 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1683454	NM_001853.4(COL9A3):c.183+2T>C	COL9A3	Pathogenic	criteria provided, single submitter
1683456	NM_001853.4(COL9A3):c.1729C>T (p.Arg577Ter)	COL9A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17138	NM_001853.4(COL9A3):c.148-2A>T	COL9A3	Pathogenic	no assertion criteria provided
17141	NM_001853.4(COL9A3):c.148-1G>A	COL9A3	Pathogenic	criteria provided, multiple submitters, no conflicts
3342250	NM_001853.4(COL9A3):c.148-2A>G	COL9A3	Pathogenic	criteria provided, single submitter
3896138	NM_001853.4(COL9A3):c.1740delinsCC (p.Gly581fs)	COL9A3	Pathogenic	criteria provided, single submitter
1705545	NM_001853.4(COL9A3):c.433G>T (p.Gly145Ter)	COL9A3	Likely pathogenic	criteria provided, single submitter
17140	NM_001853.4(COL9A3):c.183+5G>A	COL9A3	Likely pathogenic	criteria provided, single submitter
488486	NM_001853.4(COL9A3):c.183+4A>C	COL9A3	Likely pathogenic	criteria provided, single submitter
931460	NM_001853.4(COL9A3):c.184-2A>G	COL9A3	Likely pathogenic	criteria provided, single submitter
1097828	NM_001853.4(COL9A3):c.387C>T (p.Ser129=)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1221692	NM_001853.4(COL9A3):c.1918G>A (p.Glu640Lys)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1493459	NM_001853.4(COL9A3):c.1928C>T (p.Pro643Leu)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1506300	NM_001853.4(COL9A3):c.1851C>A (p.Asp617Glu)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
632378	NM_001853.4(COL9A3):c.700C>T (p.Arg234Ter)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1016227	NM_001853.4(COL9A3):c.240_248del (p.78LPG[1])	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1048783	NM_001853.4(COL9A3):c.397G>A (p.Gly133Ser)	COL9A3	Uncertain significance	no assertion criteria provided
1172686	NM_001853.4(COL9A3):c.1150C>T (p.Arg384Trp)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1214474	NM_001853.4(COL9A3):c.1547C>T (p.Pro516Leu)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1298874	NM_001853.4(COL9A3):c.1906G>A (p.Gly636Ser)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1307863	NM_001853.4(COL9A3):c.1450G>A (p.Gly484Ser)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1314117	NM_001853.4(COL9A3):c.218C>T (p.Pro73Leu)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1356138	NM_001853.4(COL9A3):c.422C>G (p.Pro141Arg)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1422100	NM_001853.4(COL9A3):c.1651G>A (p.Gly551Arg)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1426054	NM_001853.4(COL9A3):c.97C>A (p.Pro33Thr)	COL9A3	Uncertain significance	criteria provided, single submitter
1466406	NM_001853.4(COL9A3):c.1563C>A (p.Ser521Arg)	COL9A3	Uncertain significance	criteria provided, single submitter
1475803	NM_001853.4(COL9A3):c.1775C>T (p.Pro592Leu)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1686596	NM_001853.4(COL9A3):c.104G>A (p.Gly35Asp)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1979824	NM_001853.4(COL9A3):c.598G>A (p.Glu200Lys)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1991640	NM_001853.4(COL9A3):c.883G>A (p.Gly295Arg)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 2 · 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
COL9A3	Definitive	Autosomal dominant	epiphyseal dysplasia, multiple, 3	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL9A3	Orphanet:166002	Multiple epiphyseal dysplasia due to collagen 9 anomaly
COL9A3	Orphanet:250984	Autosomal recessive Stickler 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
COL9A3	HGNC:2219	ENSG00000092758	Q14050	Collagen alpha-3(IX) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL9A3	Collagen alpha-3(IX) chain	Structural component of hyaline cartilage and vitreous of the eye.

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)
COL9A3	Other/Unknown	no		Collagen, Collagen_superfamily

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
cartilage tissue	1
inferior vagus X ganglion	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL9A3	218	broad	marker	tibia, cartilage tissue, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL9A3	1,482

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL9A3	Q14050	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Collagen chain trimerization	1	259.6×	0.007	COL9A3
Signaling by PDGF	1	253.8×	0.007	COL9A3
NCAM1 interactions	1	248.3×	0.007	COL9A3
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL9A3
Collagen degradation	1	175.7×	0.007	COL9A3
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL9A3
ECM proteoglycans	1	150.3×	0.007	COL9A3
Integrin cell surface interactions	1	134.3×	0.007	COL9A3

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
COL9A3	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	COL9A3

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)
COL9A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.