Kyphomelic dysplasia

Summary

Kyphomelic dysplasia (MONDO:0008881) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 18

Clinical features

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000907	Anterior rib cupping	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0003312	Abnormal form of the vertebral bodies	Very frequent (80-99%)
HP:0003498	Disproportionate short stature	Very frequent (80-99%)
HP:0006487	Bowing of the long bones	Very frequent (80-99%)
HP:0010306	Short thorax	Very frequent (80-99%)
HP:0010561	Undulate ribs	Very frequent (80-99%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000895	Lateral clavicle hook	Frequent (30-79%)
HP:0000921	Missing ribs	Frequent (30-79%)
HP:0001376	Limitation of joint mobility	Frequent (30-79%)
HP:0001387	Joint stiffness	Frequent (30-79%)
HP:0003180	Flat acetabular roof	Frequent (30-79%)
HP:0012368	Flat face	Frequent (30-79%)
HP:0001176	Large hands	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	kyphomelic dysplasia
Mondo ID	MONDO:0008881
MeSH	C538128
OMIM	211350
Orphanet	1801
DOID	DOID:0061155
ICD-11	268821879
SNOMED CT	254096001
UMLS	C0432239
MedGen	140930
GARD	0010149
Is cancer (heuristic)	no

Also known as: congenital bowing with short bones · kyphomelic dysplasia

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › bent bone dysplasia › kyphomelic dysplasia

Related subtypes (10): Weismann-Netter syndrome, campomelic dysplasia, parastremmatic dwarfism, congenital bowing of long bones, campomelia, Cumming type, Blount disease, severe lateral tibial bowing with short stature, familial bent bone dysplasia syndrome, Stüve-Wiedemann syndrome 1, autosomal recessive combined immunodeficiency due to complete IL6ST deficiency

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3630046	NM_001901.4(CCN2):c.443G>A (p.Cys148Tyr)	CCN2	Pathogenic	no assertion criteria provided
3630047	NM_001901.4(CCN2):c.779_786del (p.Pro260fs)	CCN2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CCN2	Limited	Autosomal recessive	kyphomelic dysplasia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCN2	Orphanet:220393	Diffuse cutaneous systemic sclerosis
CCN2	Orphanet:220402	Limited cutaneous systemic sclerosis

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
CCN2	HGNC:2500	ENSG00000118523	P29279	CCN family member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCN2	CCN family member 2	Major connective tissue mitoattractant secreted by vascular endothelial cells.

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)
CCN2	Other/Unknown	no		IGFBP-like, TSP1_rpt, VWF_dom

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
ascending aorta	1
thoracic aorta	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCN2	270	ubiquitous	marker	tibia, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCN2	3,887

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCN2	P29279	78.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
RUNX3 regulates YAP1-mediated transcription	1	1427.5×	0.004	CCN2
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	761.3×	0.004	CCN2
Transcriptional regulation by RUNX3	1	271.9×	0.007	CCN2
RNA Polymerase II Transcription	1	22.5×	0.066	CCN2
Gene expression (Transcription)	1	17.8×	0.066	CCN2
Generic Transcription Pathway	1	15.1×	0.066	CCN2

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
regulation of chondrocyte differentiation	1	1404.3×	0.008	CCN2
chondrocyte proliferation	1	1053.2×	0.008	CCN2
DNA biosynthetic process	1	802.5×	0.008	CCN2
cartilage condensation	1	766.0×	0.008	CCN2
tissue homeostasis	1	561.7×	0.008	CCN2
reactive oxygen species metabolic process	1	468.1×	0.008	CCN2
positive regulation of stress fiber assembly	1	312.1×	0.009	CCN2
chondrocyte differentiation	1	300.9×	0.009	CCN2
fibroblast growth factor receptor signaling pathway	1	285.6×	0.009	CCN2
positive regulation of cell differentiation	1	267.5×	0.009	CCN2
response to wounding	1	221.7×	0.009	CCN2
epidermis development	1	210.7×	0.009	CCN2
lung development	1	198.3×	0.009	CCN2
cell-matrix adhesion	1	163.6×	0.009	CCN2
positive regulation of JNK cascade	1	163.6×	0.009	CCN2
integrin-mediated signaling pathway	1	160.5×	0.009	CCN2
osteoblast differentiation	1	121.2×	0.011	CCN2
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.015	CCN2
negative regulation of gene expression	1	69.1×	0.018	CCN2
angiogenesis	1	62.4×	0.018	CCN2
cell migration	1	61.5×	0.018	CCN2
cell adhesion	1	37.5×	0.028	CCN2
signal transduction	1	16.1×	0.062	CCN2

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
CCN2	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
CCN2	16	Binding:16

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	CCN2

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)
CCN2	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.