Stickler syndrome, type 5
disease diseaseOn this page
Also known as autosomal recessive Stickler syndrome caused by mutation in COL9A2COL9A2 autosomal recessive Stickler syndromeSTICKLER syndrome, type VSTL5
Summary
Stickler syndrome, type 5 (MONDO:0013666) 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: 21
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Stickler syndrome, type 5 |
| Mondo ID | MONDO:0013666 |
| OMIM | 614284 |
| UMLS | C3280342 |
| MedGen | 481972 |
| GARD | 0018359 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive Stickler syndrome caused by mutation in COL9A2 · COL9A2 autosomal recessive Stickler syndrome · STICKLER syndrome, type V · STL5
Data availability: 21 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › Stickler syndrome › Stickler syndrome, type 5
Related subtypes (4): Stickler syndrome type 1, Stickler syndrome type 2, Stickler syndrome, type 4, Stickler syndrome, type 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
21 retrieved; paginated sample, class counts are floors:
10 conflicting classifications of pathogenicity, 5 uncertain significance, 2 pathogenic/likely pathogenic, 1 benign, 1 benign/likely benign, 1 likely benign, 1 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 |
| 29645 | NM_001852.4(COL9A2):c.843_846+4del | COL9A2 | Pathogenic | no assertion criteria provided |
| 632106 | NM_001852.4(COL9A2):c.1242del (p.Gly415fs) | COL9A2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1007311 | NM_001852.4(COL9A2):c.1485del (p.Gly496fs) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1174415 | NM_001852.4(COL9A2):c.217C>T (p.Pro73Ser) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1199096 | NM_001852.4(COL9A2):c.682C>T (p.Pro228Ser) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1217758 | NM_001852.4(COL9A2):c.1753G>A (p.Val585Met) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 196169 | NM_001852.4(COL9A2):c.1576G>A (p.Val526Met) | 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 |
| 297302 | NM_001852.4(COL9A2):c.1123C>G (p.Arg375Gly) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 417900 | NM_001852.4(COL9A2):c.2059A>G (p.Lys687Glu) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 547939 | NM_001852.4(COL9A2):c.458C>T (p.Pro153Leu) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 689606 | NM_001852.4(COL9A2):c.1237C>T (p.Pro413Ser) | COL9A2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1209914 | NM_001852.4(COL9A2):c.1982C>G (p.Pro661Arg) | COL9A2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1498890 | NM_001852.4(COL9A2):c.749G>C (p.Gly250Ala) | COL9A2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 282805 | NM_001852.4(COL9A2):c.919G>A (p.Gly307Ser) | COL9A2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 283517 | NM_001852.4(COL9A2):c.1219C>A (p.Pro407Thr) | COL9A2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 297293 | NM_001852.4(COL9A2):c.1732C>G (p.Pro578Ala) | COL9A2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1167800 | NM_001852.4(COL9A2):c.1604-26CTCC[7] | COL9A2 | Benign | criteria provided, multiple submitters, no conflicts |
| 258371 | NM_001852.4(COL9A2):c.1323+18T>G | COL9A2 | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 258380 | NM_001852.4(COL9A2):c.1871-8G>T | COL9A2 | Likely benign | criteria provided, multiple submitters, no conflicts |
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 recessive | Stickler syndrome, type 5 | 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.
Related Atlas pages
- Cohort genes: COL9A2