Stickler syndrome, type I, nonsyndromic ocular

Summary

Stickler syndrome, type I, nonsyndromic ocular (MONDO:0012287) is a disease caused by COL2A1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COL2A1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 84

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Stickler syndrome, type I, nonsyndromic ocular
Mondo ID	MONDO:0012287
MeSH	C563709
OMIM	609508
UMLS	C1836080
MedGen	322820
GARD	0015461
Is cancer (heuristic)	no

Also known as: Stickler syndrome, type i, nonsyndromic ocular

Data availability: 84 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Stickler syndrome › Stickler syndrome type 1 › Stickler syndrome, type I, nonsyndromic ocular

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

84 retrieved; paginated sample, class counts are floors:

20 pathogenic, 17 conflicting classifications of pathogenicity, 15 likely pathogenic, 12 uncertain significance, 9 benign/likely benign, 6 pathogenic/likely pathogenic, 5 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074468	NM_001844.5(COL2A1):c.1A>G (p.Met1Val)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1224342	NM_001844.5(COL2A1):c.3121G>A (p.Gly1041Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1455692	NM_001844.5(COL2A1):c.2858del (p.Pro953fs)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17364	NM_001844.5(COL2A1):c.800G>A (p.Gly267Asp)	COL2A1	Pathogenic	criteria provided, single submitter
17366	NM_001844.5(COL2A1):c.2965C>T (p.Arg989Cys)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17383	NM_001844.5(COL2A1):c.1693C>T (p.Arg565Cys)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17384	NM_001844.5(COL2A1):c.1999C>T (p.Leu667Phe)	COL2A1	Pathogenic	no assertion criteria provided
17386	NM_001844.5(COL2A1):c.171_172del (p.Cys57_Asp58delinsTer)	COL2A1	Pathogenic	criteria provided, single submitter
17393	NM_001844.5(COL2A1):c.3508G>A (p.Gly1170Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17395	NM_001844.5(COL2A1):c.1957C>T (p.Arg653Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17399	NM_001844.5(COL2A1):c.3886+2T>C	COL2A1	Pathogenic	no assertion criteria provided
17400	NM_001844.5(COL2A1):c.141G>A (p.Trp47Ter)	COL2A1	Pathogenic	no assertion criteria provided
17401	NM_001844.5(COL2A1):c.192C>A (p.Cys64Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17402	NM_001844.5(COL2A1):c.170G>A (p.Cys57Tyr)	COL2A1	Pathogenic	no assertion criteria provided
1803193	NM_001844.5(COL2A1):c.1420-1G>A	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1805538	NM_001844.5(COL2A1):c.565G>T (p.Glu189Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
195148	NM_001844.5(COL2A1):c.258C>A (p.Cys86Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
195742	NM_001844.5(COL2A1):c.1510G>A (p.Gly504Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2859637	NM_001844.5(COL2A1):c.3085G>T (p.Gly1029Cys)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
286497	NM_001844.5(COL2A1):c.2353C>T (p.Arg785Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
3066029	NM_001844.5(COL2A1):c.696del (p.Glu232fs)	COL2A1	Pathogenic	no assertion criteria provided
3382798	NM_001844.5(COL2A1):c.3040G>A (p.Gly1014Arg)	COL2A1	Pathogenic	criteria provided, single submitter
449001	NM_001844.5(COL2A1):c.905C>T (p.Ala302Val)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4531411	NM_001844.5(COL2A1):c.2716G>T (p.Gly906Ter)	COL2A1	Pathogenic	criteria provided, single submitter
817513	NM_001844.5(COL2A1):c.2659C>T (p.Arg887Ter)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988569	NM_001844.5(COL2A1):c.2059G>A (p.Gly687Ser)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065720	NM_001844.5(COL2A1):c.3757dup (p.Ala1253fs)	COL2A1	Likely pathogenic	criteria provided, single submitter
1177519	NM_001844.5(COL2A1):c.1085_1096del (p.Ala362_Pro365del)	COL2A1	Likely pathogenic	no assertion criteria provided
1471775	NM_001844.5(COL2A1):c.1042G>T (p.Gly348Cys)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1516689	NM_001844.5(COL2A1):c.1618G>A (p.Gly540Ser)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 46 · Orphanet: 18 · 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
COL2A1	Definitive	Autosomal dominant	Stickler syndrome type 1	46

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita

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
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.

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)
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen

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
corpus epididymis	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL2A1	2,491

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL2A1	P02458	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Fibronectin matrix formation	1	571.0×	0.008	COL2A1
MET activates PTK2 signaling	1	380.7×	0.008	COL2A1
Collagen chain trimerization	1	259.6×	0.008	COL2A1
Signaling by PDGF	1	253.8×	0.008	COL2A1
NCAM1 interactions	1	248.3×	0.008	COL2A1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	COL2A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.008	COL2A1
Collagen degradation	1	175.7×	0.008	COL2A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.008	COL2A1
Non-integrin membrane-ECM interactions	1	154.3×	0.008	COL2A1
ECM proteoglycans	1	150.3×	0.008	COL2A1
Integrin cell surface interactions	1	134.3×	0.008	COL2A1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.011	COL2A1

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
otic vesicle development	1	2808.7×	0.002	COL2A1
anterior head development	1	2808.7×	0.002	COL2A1
cartilage development involved in endochondral bone morphogenesis	1	2407.4×	0.002	COL2A1
proteoglycan metabolic process	1	1872.4×	0.002	COL2A1
notochord development	1	1685.2×	0.002	COL2A1
limb bud formation	1	1532.0×	0.002	COL2A1
embryonic skeletal joint morphogenesis	1	1532.0×	0.002	COL2A1
cartilage condensation	1	766.0×	0.004	COL2A1
tissue homeostasis	1	561.7×	0.004	COL2A1
cellular response to BMP stimulus	1	561.7×	0.004	COL2A1
endochondral ossification	1	543.6×	0.004	COL2A1
extrinsic apoptotic signaling pathway in absence of ligand	1	468.1×	0.004	COL2A1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.004	COL2A1
heart morphogenesis	1	374.5×	0.005	COL2A1
chondrocyte differentiation	1	300.9×	0.005	COL2A1
inner ear morphogenesis	1	300.9×	0.005	COL2A1
cartilage development	1	251.5×	0.005	COL2A1
roof of mouth development	1	247.8×	0.005	COL2A1
collagen fibril organization	1	224.7×	0.006	COL2A1
skeletal system development	1	125.8×	0.010	COL2A1
central nervous system development	1	115.4×	0.010	COL2A1
sensory perception of sound	1	100.9×	0.011	COL2A1
regulation of gene expression	1	83.4×	0.013	COL2A1
visual perception	1	79.5×	0.013	COL2A1

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
COL2A1	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
COL2A1	2	Binding:2

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	COL2A1

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)
COL2A1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.