Epiphyseal dysplasia, multiple, 2

Summary

Epiphyseal dysplasia, multiple, 2 (MONDO:0010844) is a disease caused by COL9A2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COL9A2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 119

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epiphyseal dysplasia, multiple, 2
Mondo ID	MONDO:0010844
MeSH	C535502
OMIM	600204
DOID	DOID:0070298
UMLS	C1838429
MedGen	333092
GARD	0009791
Is cancer (heuristic)	no

Also known as: COL9A2 multiple epiphyseal dysplasia (disease) · EDM2 · epiphyseal dysplasia multiple 2 · epiphyseal dysplasia, multiple, 2 · epiphyseal dysplasia, multiple, type 2 · multiple epiphyseal dysplasia (disease) caused by mutation in COL9A2 · multiple epiphyseal dysplasia 2

Data availability: 119 ClinVar variants · 2 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, 2

Related subtypes (2): epiphyseal dysplasia, multiple, 3, 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

119 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 30 conflicting classifications of pathogenicity, 25 benign, 8 benign/likely benign, 8 likely benign, 7 likely pathogenic, 4 pathogenic/likely pathogenic, 4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1194069	NM_001852.4(COL9A2):c.1506del (p.Asn503fs)	COL9A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17142	NM_001852.4(COL9A2):c.186+2T>C	COL9A2	Pathogenic	no assertion criteria provided
17144	NM_001852.4(COL9A2):c.186+5G>C	COL9A2	Pathogenic	criteria provided, single submitter
17146	NM_001852.4(COL9A2):c.186G>C (p.Pro62=)	COL9A2	Pathogenic	criteria provided, single submitter
1999456	NM_001852.4(COL9A2):c.186+1G>A	COL9A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427128	NM_001852.4(COL9A2):c.186G>A (p.Pro62=)	COL9A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4536678	NM_001852.4(COL9A2):c.282del (p.Met95fs)	COL9A2	Pathogenic	criteria provided, single submitter
632106	NM_001852.4(COL9A2):c.1242del (p.Gly415fs)	COL9A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320223	NM_001852.4(COL9A2):c.1107+1G>T	COL9A2	Likely pathogenic	criteria provided, single submitter
3065674	NM_001852.4(COL9A2):c.1162G>A (p.Gly388Ser)	COL9A2	Likely pathogenic	criteria provided, single submitter
4081923	NM_001852.4(COL9A2):c.1053+2T>C	COL9A2	Likely pathogenic	no assertion criteria provided
4280632	NM_001852.4(COL9A2):c.1067del (p.Pro356fs)	COL9A2	Likely pathogenic	criteria provided, single submitter
4291835	NM_001852.4(COL9A2):c.150+1G>A	COL9A2	Likely pathogenic	criteria provided, single submitter
4292083	NM_001852.4(COL9A2):c.340-2A>G	COL9A2	Likely pathogenic	criteria provided, single submitter
4813074	NM_001852.4(COL9A2):c.186+5G>T	COL9A2	Likely pathogenic	criteria provided, single submitter
1007311	NM_001852.4(COL9A2):c.1485del (p.Gly496fs)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195478	NM_001852.4(COL9A2):c.1041C>T (p.Gly347=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196777	NM_001852.4(COL9A2):c.2019G>A (p.Ser673=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196778	NM_001852.4(COL9A2):c.1982C>T (p.Pro661Leu)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258369	NM_001852.4(COL9A2):c.1188G>A (p.Val396=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258381	NM_001852.4(COL9A2):c.1902C>T (p.Asn634=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291230	NM_001852.4(COL9A2):c.2058C>T (p.Ile686=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297291	NM_001852.4(COL9A2):c.1834G>A (p.Gly612Arg)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297294	NM_001852.4(COL9A2):c.1609C>T (p.Leu537=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297295	NM_001852.4(COL9A2):c.1599G>T (p.Leu533=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297297	NM_001852.4(COL9A2):c.1400A>G (p.Gln467Arg)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297299	NM_001852.4(COL9A2):c.1162-3C>T	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297302	NM_001852.4(COL9A2):c.1123C>G (p.Arg375Gly)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297303	NM_001852.4(COL9A2):c.1054-15A>G	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297305	NM_001852.4(COL9A2):c.942G>A (p.Thr314=)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
COL9A2	Definitive	Autosomal dominant	epiphyseal dysplasia, multiple, 2	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL9A2	Orphanet:166002	Multiple epiphyseal dysplasia due to collagen 9 anomaly
COL9A2	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
COL9A2	HGNC:2218	ENSG00000049089	Q14055	Collagen alpha-2(IX) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL9A2	Collagen alpha-2(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)
COL9A2	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
C1 segment of cervical spinal cord	1
adenohypophysis	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL9A2	213	broad	marker	C1 segment of cervical spinal cord, tibia, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL9A2	1,419

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL9A2	Q14055	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	COL9A2
Signaling by PDGF	1	253.8×	0.007	COL9A2
NCAM1 interactions	1	248.3×	0.007	COL9A2
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL9A2
Collagen degradation	1	175.7×	0.007	COL9A2
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL9A2
ECM proteoglycans	1	150.3×	0.007	COL9A2
Integrin cell surface interactions	1	134.3×	0.007	COL9A2

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
skeletal system development	1	125.8×	0.008	COL9A2

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
COL9A2	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	COL9A2

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)
COL9A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.