Fibrochondrogenesis 1

Summary

Fibrochondrogenesis 1 (MONDO:0009226) is a disease caused by COL11A1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: COL11A1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 209

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fibrochondrogenesis 1
Mondo ID	MONDO:0009226
OMIM	228520
DOID	DOID:0080672
UMLS	C3278138
MedGen	479768
GARD	0024653
Is cancer (heuristic)	no

Also known as: COL11A1 fibrochondrogenesis · FBCG1 · fibrochondrogenesis 1 · fibrochondrogenesis caused by mutation in COL11A1 · fibrochondrogenesis type 1

Data availability: 209 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › fibrochondrogenesis › fibrochondrogenesis 1

Related subtypes (1): fibrochondrogenesis 2

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

209 retrieved; paginated sample, class counts are floors:

85 conflicting classifications of pathogenicity, 58 uncertain significance, 28 benign, 23 benign/likely benign, 5 pathogenic/likely pathogenic, 4 likely benign, 3 likely pathogenic, 2 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032776	NM_001854.4(COL11A1):c.3816+2dup	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1216773	NM_001854.4(COL11A1):c.2513G>A (p.Gly838Glu)	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1304338	NM_001854.4(COL11A1):c.2241+5G>T	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324096	NM_001854.4(COL11A1):c.1245+1G>A	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3385087	NM_001854.4(COL11A1):c.1245+1G>T	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620141	NM_001854.4(COL11A1):c.4084C>T (p.Arg1362Ter)	COL11A1	Pathogenic	criteria provided, multiple submitters, no conflicts
801531	NM_001854.4(COL11A1):c.3168+2_3168+12del	COL11A1	Pathogenic	criteria provided, single submitter
1179083	NM_001854.4(COL11A1):c.4186G>T (p.Gly1396Cys)	COL11A1	Likely pathogenic	criteria provided, single submitter
3775265	NM_001854.4(COL11A1):c.2655+1G>A	COL11A1	Likely pathogenic	criteria provided, single submitter
973212	NM_001854.4(COL11A1):c.1168G>T (p.Glu390Ter)	COL11A1	Likely pathogenic	criteria provided, single submitter
1032777	NM_001854.4(COL11A1):c.898-185T>C	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038628	NM_001854.4(COL11A1):c.3692G>T (p.Gly1231Val)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1206960	NM_001854.4(COL11A1):c.3068C>A (p.Ala1023Glu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1300948	NM_001854.4(COL11A1):c.2644C>T (p.Arg882Cys)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1314615	NM_001854.4(COL11A1):c.565C>T (p.Pro189Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357917	NM_001854.4(COL11A1):c.2285G>A (p.Arg762Gln)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418086	NM_001854.4(COL11A1):c.4709T>C (p.Leu1570Pro)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1508766	NM_001854.4(COL11A1):c.5231A>G (p.Tyr1744Cys)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
166922	NM_001854.4(COL11A1):c.4032G>A (p.Pro1344=)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1961384	NM_001854.4(COL11A1):c.2203C>G (p.Pro735Ala)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197911	NM_001854.4(COL11A1):c.3811G>T (p.Val1271Leu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197964	NM_001854.4(COL11A1):c.4057G>A (p.Ala1353Thr)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198301	NM_001854.4(COL11A1):c.4468A>G (p.Ile1490Val)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198360	NM_001854.4(COL11A1):c.5198G>A (p.Arg1733His)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198474	NM_001854.4(COL11A1):c.965C>T (p.Pro322Leu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198777	NM_001854.4(COL11A1):c.1021G>C (p.Glu341Gln)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258457	NM_001854.4(COL11A1):c.3277-13A>C	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289407	NM_001854.4(COL11A1):c.2322G>A (p.Lys774=)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289661	NM_001854.4(COL11A1):c.3639G>A (p.Gly1213=)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291475	NM_001854.4(COL11A1):c.*1227T>A	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 5 · 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
COL11A1	Definitive	Autosomal recessive	fibrochondrogenesis 1	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	gencc,clinvar
AMY2A	HGNC:477	ENSG00000243480	P04746	Pancreatic alpha-amylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
AMY2A	Enzyme (other)	yes	3.2.1.1	Alpha_amylase, GH13_cat_dom, A-amylase/branching_C

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
periodontal ligament	1
tibia	1
body of pancreas	1
islet of Langerhans	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
AMY2A	125	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL11A1	2,433
AMY2A	1,844

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AMY2A	P04746	51

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A1	P12107	53.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Digestion of dietary carbohydrate	1	475.8×	0.014	AMY2A
Digestion and absorption	1	380.7×	0.014	AMY2A
Digestion	1	285.5×	0.014	AMY2A
MET activates PTK2 signaling	1	190.3×	0.014	COL11A1
Developmental Lineage of Pancreatic Acinar Cells	1	150.3×	0.014	AMY2A
Collagen chain trimerization	1	129.8×	0.014	COL11A1
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.014	COL11A1
Developmental Cell Lineages	1	112.0×	0.014	AMY2A
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.014	COL11A1
Collagen degradation	1	87.8×	0.014	COL11A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.014	COL11A1
Non-integrin membrane-ECM interactions	1	77.2×	0.014	COL11A1
Developmental Biology	1	7.2×	0.134	AMY2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tendon development	1	2106.5×	0.003	COL11A1
polysaccharide digestion	1	2106.5×	0.003	AMY2A
carbohydrate catabolic process	1	1685.2×	0.003	AMY2A
proteoglycan metabolic process	1	936.2×	0.004	COL11A1
chondrocyte development	1	468.1×	0.005	COL11A1
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.005	COL11A1
cartilage condensation	1	383.0×	0.005	COL11A1
ventricular cardiac muscle tissue morphogenesis	1	351.1×	0.005	COL11A1
endodermal cell differentiation	1	247.8×	0.007	COL11A1
embryonic skeletal system morphogenesis	1	195.9×	0.008	COL11A1
inner ear morphogenesis	1	150.5×	0.009	COL11A1
collagen fibril organization	1	112.3×	0.011	COL11A1
carbohydrate metabolic process	1	68.0×	0.017	AMY2A
sensory perception of sound	1	50.5×	0.021	COL11A1
visual perception	1	39.8×	0.025	COL11A1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
AMY2A	ACARBOSE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AMY2A	1	4
COL11A1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ACARBOSE	4	AMY2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AMY2A	20	Binding:15, Functional:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AMY2A	3.2.1.1	alpha-amylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
ACARBOSE	4	AMY2A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	AMY2A
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	COL11A1

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)
COL11A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.