Hypochondrogenesis

Summary

Hypochondrogenesis (MONDO:0019669) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 5
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypochondrogenesis
Mondo ID	MONDO:0019669
MeSH	C563007
Orphanet	93297
DOID	DOID:0080044
ICD-11	1494246635
UMLS	C0542428
MedGen	107448
GARD	0016815
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

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 › achondrogenesis › hypochondrogenesis

Related subtypes (4): achondrogenesis type IA, achondrogenesis type II, acromesomelic dysplasia 2A, achondrogenesis type IB

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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
17352	NM_001844.5(COL2A1):c.3220G>A (p.Gly1074Ser)	COL2A1	Pathogenic	no assertion criteria provided
17357	NM_001844.5(COL2A1):c.2320G>A (p.Gly774Ser)	COL2A1	Pathogenic	no assertion criteria provided
17359	NM_001844.5(COL2A1):c.3158G>A (p.Gly1053Glu)	COL2A1	Pathogenic	no assertion criteria provided
265429	NM_001844.5(COL2A1):c.2833G>A (p.Gly945Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1202957	NM_001844.5(COL2A1):c.1679G>C (p.Arg560Pro)	COL2A1	Uncertain significance	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	Supportive	Autosomal dominant	hypochondrogenesis	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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05408715	Not specified	RECRUITING	A Natural History Study in Children With a Type II Collagen Disorder With Short Stature