chondrodysplasia Blomstrand type

Summary

chondrodysplasia Blomstrand type (MONDO:0008970) is a disease caused by PTH1R (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PTH1R (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 131
• Phenotypes (HPO): 37

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000520	Proptosis	Very frequent (80-99%)
HP:0000773	Short ribs	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000916	Broad clavicles	Very frequent (80-99%)
HP:0000926	Platyspondyly	Very frequent (80-99%)
HP:0001538	Protuberant abdomen	Very frequent (80-99%)
HP:0001561	Polyhydramnios	Very frequent (80-99%)
HP:0001622	Premature birth	Very frequent (80-99%)
HP:0002089	Pulmonary hypoplasia	Very frequent (80-99%)
HP:0003015	Flared metaphysis	Very frequent (80-99%)
HP:0003021	Metaphyseal cupping	Very frequent (80-99%)
HP:0003027	Mesomelia	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0005616	Accelerated skeletal maturation	Very frequent (80-99%)
HP:0005716	Lethal skeletal dysplasia	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0006402	Distal shortening of limbs	Very frequent (80-99%)
HP:0006660	Aplastic clavicles	Very frequent (80-99%)
HP:0008905	Rhizomelia	Very frequent (80-99%)
HP:0008921	Neonatal short-limb short stature	Very frequent (80-99%)
HP:0010306	Short thorax	Very frequent (80-99%)
HP:0011001	Increased bone mineral density	Very frequent (80-99%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000695	Natal tooth	Frequent (30-79%)
HP:0001789	Hydrops fetalis	Frequent (30-79%)
HP:0006487	Bowing of the long bones	Frequent (30-79%)
HP:0010049	Short metacarpal	Frequent (30-79%)
HP:0010808	Protruding tongue	Frequent (30-79%)
HP:0100240	Synostosis of joints	Frequent (30-79%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chondrodysplasia Blomstrand type
Mondo ID	MONDO:0008970
MeSH	C537914
OMIM	215045
Orphanet	50945
DOID	DOID:0060387
NCIT	C131420
UMLS	C1859148
MedGen	395189
GARD	0000914
Is cancer (heuristic)	no

Also known as: BLC · Blomstrand chondrodysplasia · Blomstrand lethal chondrodysplasia · Blomstrand lethal osteochondrodysplasia · Blomstrand osteochondrodysplasia · Blomstrand type chondrodysplasia · Blomstrand’s lethal chondrodysplasia · BOCD · chondrodysplasia, Blomstrand type

Data availability: 131 ClinVar variants · 5 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 › neonatal osteosclerotic dysplasia › chondrodysplasia Blomstrand type

Related subtypes (4): Caffey disease, lethal osteosclerotic bone dysplasia, desmosterolosis, dysplastic cortical hyperostosis

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

131 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 21 conflicting classifications of pathogenicity, 13 benign/likely benign, 8 likely benign, 5 pathogenic, 4 likely pathogenic, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13745	NM_000316.3(PTH1R):c.395C>T (p.Pro132Leu)	LOC129936652	Pathogenic	criteria provided, single submitter
13744	NM_000316.3(PTH1R):c.1148G>A (p.Arg383Gln)	PTH1R	Pathogenic	criteria provided, single submitter
13746	NM_000316.3(PTH1R):c.1093del (p.Val365fs)	PTH1R	Pathogenic	criteria provided, single submitter
13750	NM_000316.3(PTH1R):c.310C>T (p.Arg104Ter)	PTH1R	Pathogenic	criteria provided, single submitter
13751	NM_000316.3(PTH1R):c.1049+29C>T	PTH1R	Pathogenic	no assertion criteria provided
4086058	NM_000316.3(PTH1R):c.356C>T (p.Pro119Leu)	LOC129936652	Likely pathogenic	criteria provided, single submitter
3589193	NM_000316.3(PTH1R):c.75+1del	PTH1R	Likely pathogenic	criteria provided, single submitter
3589206	NM_000316.3(PTH1R):c.735C>G (p.Tyr245Ter)	PTH1R	Likely pathogenic	criteria provided, single submitter
3589209	NM_000316.3(PTH1R):c.892T>G (p.Trp298Gly)	PTH1R	Likely pathogenic	criteria provided, single submitter
1050981	NM_000316.3(PTH1R):c.1645G>A (p.Glu549Lys)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1410640	NM_000316.3(PTH1R):c.311G>A (p.Arg104Gln)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2707211	NM_000316.3(PTH1R):c.1144G>A (p.Val382Ile)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345575	NM_000316.3(PTH1R):c.75+9C>T	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345577	NM_000316.3(PTH1R):c.128G>A (p.Arg43His)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345578	NM_000316.3(PTH1R):c.144C>T (p.Cys48=)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345580	NM_000316.3(PTH1R):c.226G>C (p.Gly76Arg)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345582	NM_000316.3(PTH1R):c.313+4C>T	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345591	NM_000316.3(PTH1R):c.876G>T (p.Leu292=)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345592	NM_000316.3(PTH1R):c.1050-3dup	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345593	NM_000316.3(PTH1R):c.1152G>T (p.Val384=)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345594	NM_000316.3(PTH1R):c.1255G>A (p.Val419Ile)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345598	NM_000316.3(PTH1R):c.1427G>A (p.Arg476His)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345601	NM_000316.3(PTH1R):c.1644C>T (p.Leu548=)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
64398	NM_000316.3(PTH1R):c.1304C>T (p.Thr435Met)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
733286	NM_000316.3(PTH1R):c.1212-10G>A	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
899444	NM_000316.3(PTH1R):c.449G>A (p.Arg150His)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900527	NM_000316.3(PTH1R):c.137C>A (p.Ala46Asp)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900571	NM_000316.3(PTH1R):c.638+11C>A	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902323	NM_000316.3(PTH1R):c.1695C>T (p.Asn565=)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903131	NM_000316.3(PTH1R):c.1182C>T (p.Ala394=)	PTH1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 6 · 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
PTH1R	Definitive	Autosomal dominant	metaphyseal chondrodysplasia, Jansen type	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTH1R	Orphanet:296	Ollier disease
PTH1R	Orphanet:33067	Metaphyseal chondrodysplasia, Jansen type
PTH1R	Orphanet:412206	Primary failure of tooth eruption
PTH1R	Orphanet:50945	Blomstrand lethal chondrodysplasia
PTH1R	Orphanet:79106	Eiken syndrome
PLCB4	Orphanet:137888	Auriculocondylar syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PTH1R	HGNC:9608	ENSG00000160801	Q03431	Parathyroid hormone/parathyroid hormone-related peptide receptor	gencc,clinvar
MYL3	HGNC:7584	ENSG00000160808	P08590	Myosin light chain 3	clinvar
PLCB4	HGNC:9059	ENSG00000101333	Q15147	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTH1R	Parathyroid hormone/parathyroid hormone-related peptide receptor	G-protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH).
MYL3	Myosin light chain 3	Regulatory light chain of myosin.
PLCB4	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	Activated phosphatidylinositol-specific phospholipase C enzymes catalyze the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) involved in G-protein coupled receptor signaling pathways.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
GPCR	1	8.0×	0.345
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTH1R	GPCR	yes		GPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_parathyroid_rcpt
MYL3	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, CALM/Myosin/TropC-like
PLCB4	Enzyme (other)	yes	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
metanephros cortex	1
tibia	1
apex of heart	1
heart right ventricle	1
hindlimb stylopod muscle	1
lateral nuclear group of thalamus	1
parotid gland	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTH1R	219	broad	marker	adult mammalian kidney, metanephros cortex, tibia
MYL3	198	broad	marker	apex of heart, heart right ventricle, hindlimb stylopod muscle
PLCB4	273	ubiquitous	marker	parotid gland, lateral nuclear group of thalamus, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYL3	2,255
PTH1R	1,633
PLCB4	1,595

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTH1R	Q03431	48
MYL3	P08590	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLCB4	Q15147	86.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of IP3 and IP4 in the cytosol	1	141.0×	0.026	PLCB4
Striated Muscle Contraction	1	102.9×	0.026	MYL3
PLC beta mediated events	1	88.5×	0.026	PLCB4
Class B/2 (Secretin family receptors)	1	63.4×	0.027	PTH1R
Muscle contraction	1	25.7×	0.047	MYL3
G alpha (s) signalling events	1	24.4×	0.047	PTH1R
G alpha (q) signalling events	1	19.1×	0.051	PLCB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phospholipase C-activating endothelin receptor signaling pathway	1	5617.3×	0.005	PLCB4
positive regulation of inositol phosphate biosynthetic process	1	802.5×	0.014	PTH1R
regulation of striated muscle contraction	1	702.2×	0.014	MYL3
regulation of the force of heart contraction	1	330.4×	0.014	MYL3
osteoblast development	1	330.4×	0.014	PTH1R
phosphatidylinositol metabolic process	1	295.6×	0.014	PLCB4
phosphatidylinositol-mediated signaling	1	234.1×	0.014	PLCB4
ventricular cardiac muscle tissue morphogenesis	1	234.1×	0.014	MYL3
G protein-coupled receptor signaling pathway	2	24.2×	0.014	PTH1R, PLCB4
bone resorption	1	193.7×	0.015	PTH1R
cell maturation	1	147.8×	0.018	PTH1R
cardiac muscle contraction	1	133.8×	0.018	MYL3
release of sequestered calcium ion into cytosol	1	114.6×	0.018	PLCB4
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	112.3×	0.018	PTH1R
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1	104.0×	0.018	PTH1R
chondrocyte differentiation	1	100.3×	0.018	PTH1R
skeletal muscle tissue development	1	96.8×	0.018	MYL3
bone mineralization	1	90.6×	0.018	PTH1R
lipid catabolic process	1	81.4×	0.019	PLCB4
muscle contraction	1	69.3×	0.021	MYL3
intracellular calcium ion homeostasis	1	48.4×	0.028	PTH1R
phospholipase C-activating G protein-coupled receptor signaling pathway	1	43.9×	0.030	PTH1R
skeletal system development	1	41.9×	0.030	PTH1R
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	37.7×	0.032	PTH1R
cell population proliferation	1	34.2×	0.034	PTH1R
in utero embryonic development	1	24.0×	0.046	PTH1R
cell surface receptor signaling pathway	1	21.4×	0.050	PTH1R
negative regulation of cell population proliferation	1	14.0×	0.072	PTH1R
positive regulation of cell population proliferation	1	11.2×	0.087	PTH1R

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
PTH1R	ABALOPARATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTH1R	3	4
MYL3	0	0
PLCB4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ABALOPARATIDE	4	PTH1R
TERIPARATIDE	4	PTH1R
PCO-371	1	PTH1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTH1R	59	Functional:42, Binding:17

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLCB4	3.1.4.11	phosphoinositide phospholipase C

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

3 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)
ABALOPARATIDE	4	PTH1R
TERIPARATIDE	4	PTH1R
PCO-371	1	PTH1R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PTH1R
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	PLCB4
E	Difficult family or no structure, no drug	1	MYL3

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MYL3	0	—
PLCB4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.