Stickler syndrome, type 6

Summary

Stickler syndrome, type 6 (MONDO:0031047) 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: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Stickler syndrome, type 6
Mondo ID	MONDO:0031047
OMIM	620022
UMLS	C5774207
MedGen	1823980
GARD	0025684
Is cancer (heuristic)	no

Also known as: Stickler syndrome, type VI · STL6

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Stickler syndrome › Stickler syndrome, type 6

Related subtypes (4): Stickler syndrome type 1, Stickler syndrome type 2, Stickler syndrome, type 4, Stickler syndrome, type 5

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

19 retrieved; paginated sample, class counts are floors:

7 pathogenic, 6 uncertain significance, 3 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322153	NM_001853.4(COL9A3):c.647dup (p.Gly217fs)	COL9A3	Pathogenic	no assertion criteria provided
1462627	NM_001853.4(COL9A3):c.107_116del (p.Pro36fs)	COL9A3	Pathogenic	criteria provided, single submitter
161450	NM_001853.4(COL9A3):c.1176_1198del (p.Gln393fs)	COL9A3	Pathogenic	no assertion criteria provided
1683455	NM_001853.4(COL9A3):c.268C>T (p.Arg90Ter)	COL9A3	Pathogenic	criteria provided, multiple submitters, no conflicts
1683456	NM_001853.4(COL9A3):c.1729C>T (p.Arg577Ter)	COL9A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1703482	NM_001853.4(COL9A3):c.1204C>T (p.Arg402Ter)	COL9A3	Pathogenic	criteria provided, single submitter
1703483	NM_001853.4(COL9A3):c.355del (p.Leu119fs)	COL9A3	Pathogenic	no assertion criteria provided
520722	NM_001853.4(COL9A3):c.1411C>T (p.Arg471Ter)	COL9A3	Pathogenic	criteria provided, multiple submitters, no conflicts
3773688	NM_001853.4(COL9A3):c.1486G>C (p.Gly496Arg)	COL9A3	Likely pathogenic	criteria provided, single submitter
4526378	NM_001853.4(COL9A3):c.1A>G (p.Met1Val)	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
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
1016227	NM_001853.4(COL9A3):c.240_248del (p.78LPG[1])	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1172686	NM_001853.4(COL9A3):c.1150C>T (p.Arg384Trp)	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
1466406	NM_001853.4(COL9A3):c.1563C>A (p.Ser521Arg)	COL9A3	Uncertain significance	criteria provided, single submitter
1991640	NM_001853.4(COL9A3):c.883G>A (p.Gly295Arg)	COL9A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2090993	NM_001853.4(COL9A3):c.1369-3C>G	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 recessive	Stickler syndrome, type 6	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.