Diaphanospondylodysostosis

Summary

Diaphanospondylodysostosis (MONDO:0011946) is a disease caused by BMPER (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: BMPER (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 126
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		18	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000921	Missing ribs	Very frequent (80-99%)
HP:0002098	Respiratory distress	Very frequent (80-99%)
HP:0002475	Myelomeningocele	Very frequent (80-99%)
HP:0003275	Narrow pelvis bone	Very frequent (80-99%)
HP:0004599	Absent or minimally ossified vertebral bodies	Very frequent (80-99%)
HP:0005562	Multiple renal cysts	Very frequent (80-99%)
HP:0005640	Abnormal vertebral segmentation and fusion	Very frequent (80-99%)
HP:0010306	Short thorax	Very frequent (80-99%)
HP:0100625	Enlarged thorax	Very frequent (80-99%)
HP:0000175	Cleft palate	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	diaphanospondylodysostosis
Mondo ID	MONDO:0011946
MeSH	C564305
OMIM	608022
Orphanet	66637
ICD-11	508093071
SNOMED CT	721094006
UMLS	C1842691
MedGen	374993
GARD	0016674
Is cancer (heuristic)	no

Also known as: diaphanospondylodysostosis · vertebral ossification, defect in, with nephrogenic rests

Data availability: 126 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › spondylodysplastic dysplasia › diaphanospondylodysostosis

Related subtypes (8): platyspondylic dysplasia, Torrance type, spondylocarpotarsal synostosis syndrome, skeletal dysplasia-intellectual disability syndrome, spondylocamptodactyly syndrome, brachyolmia, achondrogenesis, skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome, severe spondylodysplastic dysplasia

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

126 retrieved; paginated sample, class counts are floors:

68 uncertain significance, 25 benign, 15 conflicting classifications of pathogenicity, 5 pathogenic, 4 likely pathogenic, 4 likely benign, 4 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30742	NM_001365308.1(BMPER):c.925C>T (p.Gln309Ter)	BMPER	Pathogenic	criteria provided, multiple submitters, no conflicts
30743	NM_001365308.1(BMPER):c.26_35delinsAGACCAGAGCGGCG (p.Ala9fs)	BMPER	Pathogenic	no assertion criteria provided
30744	NM_001365308.1(BMPER):c.1078+5G>A	BMPER	Pathogenic	no assertion criteria provided
30745	NM_001365308.1(BMPER):c.1109C>T (p.Pro370Leu)	BMPER	Pathogenic	no assertion criteria provided
30746	NM_001365308.1(BMPER):c.1638T>A (p.Cys546Ter)	BMPER	Pathogenic	no assertion criteria provided
559441	NM_001365308.1(BMPER):c.410T>A (p.Val137Asp)	BMPER	Pathogenic/Likely pathogenic	no assertion criteria provided
2437599	NM_001365308.1(BMPER):c.721C>T (p.Arg241Ter)	BMPER	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3594596	NM_001365308.1(BMPER):c.403-2A>C	BMPER	Likely pathogenic	criteria provided, single submitter
3594597	NM_001365308.1(BMPER):c.1075G>T (p.Glu359Ter)	BMPER	Likely pathogenic	criteria provided, single submitter
3765626	NM_001365308.1(BMPER):c.531_535dup (p.Phe179fs)	BMPER	Likely pathogenic	criteria provided, single submitter
1360194	NM_001365308.1(BMPER):c.116C>G (p.Ala39Gly)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360099	NM_001365308.1(BMPER):c.372G>A (p.Pro124=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360109	NM_001365308.1(BMPER):c.1248G>A (p.Ser416=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360110	NM_001365308.1(BMPER):c.1323C>T (p.Asn441=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360116	NM_001365308.1(BMPER):c.1818C>A (p.Thr606=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360119	NM_001365308.1(BMPER):c.1978G>A (p.Val660Ile)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
402429	NM_001365308.1(BMPER):c.220A>G (p.Asn74Asp)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
791539	NM_001365308.1(BMPER):c.1974G>A (p.Pro658=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909182	NM_001365308.1(BMPER):c.1902G>C (p.Val634=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909183	NM_001365308.1(BMPER):c.1906G>A (p.Asp636Asn)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910219	NM_001365308.1(BMPER):c.390A>C (p.Leu130=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910221	NM_001365308.1(BMPER):c.403-13T>C	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911114	NM_001365308.1(BMPER):c.493+5C>T	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911115	NM_001365308.1(BMPER):c.664C>T (p.Pro222Ser)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911318	NM_001365308.1(BMPER):c.1311C>T (p.Thr437=)	BMPER	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1395014	NM_001365308.1(BMPER):c.229G>A (p.Val77Met)	BMPER	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679888	NM_001365308.1(BMPER):c.1124T>C (p.Phe375Ser)	BMPER	Uncertain significance	criteria provided, multiple submitters, no conflicts
2180879	NM_001365308.1(BMPER):c.1744C>T (p.Arg582Trp)	BMPER	Uncertain significance	criteria provided, multiple submitters, no conflicts
2688673	NM_001365308.1(BMPER):c.927+6T>A	BMPER	Uncertain significance	criteria provided, single submitter
2688674	NM_001365308.1(BMPER):c.832T>G (p.Cys278Gly)	BMPER	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
BMPER	Definitive	Autosomal recessive	diaphanospondylodysostosis	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPER	Orphanet:66637	Diaphanospondylodysostosis

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
BMPER	HGNC:24154	ENSG00000164619	Q8N8U9	BMP-binding endothelial regulator protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMPER	BMP-binding endothelial regulator protein	Inhibitor of bone morphogenetic protein (BMP) function, it may regulate BMP responsiveness of osteoblasts and chondrocytes.

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)
BMPER	Other/Unknown	no		VWF_dom, VWF_type-D, TIL_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
prefrontal cortex	1
right lung	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMPER	166	broad	marker	upper lobe of left lung, prefrontal cortex, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMPER	1,600

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BMPER	Q8N8U9	80.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	2407.4×	0.003	BMPER
regulation of endothelial cell migration	1	2106.5×	0.003	BMPER
endothelial cell activation	1	1685.2×	0.003	BMPER
SMAD protein signal transduction	1	732.7×	0.004	BMPER
positive regulation of sprouting angiogenesis	1	674.1×	0.004	BMPER
ureteric bud development	1	455.5×	0.004	BMPER
regulation of angiogenesis	1	421.3×	0.004	BMPER
positive regulation of SMAD protein signal transduction	1	383.0×	0.004	BMPER
blood vessel development	1	374.5×	0.004	BMPER
inner ear development	1	374.5×	0.004	BMPER
negative regulation of BMP signaling pathway	1	290.6×	0.004	BMPER
regulation of protein localization	1	205.5×	0.005	BMPER
BMP signaling pathway	1	200.6×	0.005	BMPER
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.012	BMPER

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPER	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	BMPER

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)
BMPER	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.