Fibrochondrogenesis 2

Summary

Fibrochondrogenesis 2 (MONDO:0013795) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 199

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fibrochondrogenesis 2
Mondo ID	MONDO:0013795
OMIM	614524
DOID	DOID:0080673
UMLS	C3281128
MedGen	482758
GARD	0015815
Is cancer (heuristic)	no

Also known as: COL11A2 fibrochondrogenesis · FBCG2 · fibrochondrogenesis 2 · fibrochondrogenesis caused by mutation in COL11A2 · fibrochondrogenesis type 2

Data availability: 199 ClinVar variants.

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 2

Related subtypes (1): fibrochondrogenesis 1

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

199 retrieved; paginated sample, class counts are floors:

85 conflicting classifications of pathogenicity, 48 uncertain significance, 24 benign/likely benign, 19 benign, 7 likely benign, 7 likely pathogenic, 5 pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1252015	NM_080680.3(COL11A2):c.1871dup (p.Gly625fs)	COL11A2	Pathogenic	no assertion criteria provided
17128	NM_080680.3(COL11A2):c.3991C>T (p.Arg1331Ter)	COL11A2	Pathogenic	criteria provided, multiple submitters, no conflicts
2757004	NM_080680.3(COL11A2):c.3329dup (p.Gly1111fs)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2913625	NM_080680.3(COL11A2):c.4798C>T (p.Arg1600Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29650	NM_080680.3(COL11A2):c.1719+1dup	COL11A2	Pathogenic	no assertion criteria provided
29651	NM_080680.3(COL11A2):c.2902_2910del (p.Asp968_Gly970del)	COL11A2	Pathogenic	no assertion criteria provided
3017031	NM_080680.3(COL11A2):c.1297C>T (p.Arg433Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
423882	NM_080680.3(COL11A2):c.3058C>T (p.Arg1020Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807387	NM_080680.3(COL11A2):c.2087_2090del (p.Glu696fs)	COL11A2	Pathogenic	criteria provided, single submitter
3593490	NM_080680.3(COL11A2):c.4081A>T (p.Lys1361Ter)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593492	NM_080680.3(COL11A2):c.3746G>A (p.Gly1249Glu)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593493	NM_080680.3(COL11A2):c.2734_2736+14del	COL11A2	Likely pathogenic	criteria provided, single submitter
3593494	NM_080680.3(COL11A2):c.2589dup (p.Ser864fs)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593495	NM_080680.3(COL11A2):c.2567G>A (p.Gly856Glu)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593497	NM_080680.3(COL11A2):c.2062G>A (p.Gly688Arg)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593499	NM_080680.3(COL11A2):c.129_132dup (p.Asp45delinsProTer)	COL11A2	Likely pathogenic	criteria provided, single submitter
1129450	NM_080680.3(COL11A2):c.2220G>T (p.Glu740Asp)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1200125	NM_080680.3(COL11A2):c.973G>A (p.Asp325Asn)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1213287	NM_080680.3(COL11A2):c.1999G>A (p.Gly667Ser)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1375471	NM_080680.3(COL11A2):c.1399G>A (p.Val467Met)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1398032	NM_080680.3(COL11A2):c.2179G>A (p.Gly727Arg)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1524943	NM_080680.3(COL11A2):c.1726A>G (p.Thr576Ala)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162976	NM_080680.3(COL11A2):c.4683A>G (p.Thr1561=)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162981	NM_080680.3(COL11A2):c.4040C>A (p.Pro1347Gln)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162992	NM_080680.3(COL11A2):c.2186G>A (p.Arg729Gln)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162993	NM_080680.3(COL11A2):c.1287C>T (p.Gly429=)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
17129	NM_080680.3(COL11A2):c.1861C>A (p.Pro621Thr)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178321	NM_080680.3(COL11A2):c.5000G>A (p.Arg1667His)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178325	NM_080680.3(COL11A2):c.3616C>T (p.Leu1206=)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178326	NM_080680.3(COL11A2):c.3576C>T (p.Gly1192=)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.

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)
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen

Expression context

Cohort genes with no expression data: 0.

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
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL11A2	1,583

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A2	P13942	50.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
MET activates PTK2 signaling	1	380.7×	0.006	COL11A2
Collagen chain trimerization	1	259.6×	0.006	COL11A2
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.006	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.006	COL11A2
Collagen degradation	1	175.7×	0.006	COL11A2
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	COL11A2
Non-integrin membrane-ECM interactions	1	154.3×	0.006	COL11A2

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
soft palate development	1	3370.4×	0.002	COL11A2
cartilage development	1	251.5×	0.007	COL11A2
roof of mouth development	1	247.8×	0.007	COL11A2
collagen fibril organization	1	224.7×	0.007	COL11A2
skeletal system development	1	125.8×	0.010	COL11A2
sensory perception of sound	1	100.9×	0.010	COL11A2

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
COL11A2	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	COL11A2

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)
COL11A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.