Osteogenesis imperfecta type 13

Summary

Osteogenesis imperfecta type 13 (MONDO:0013924) is a disease caused by BMP1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BMP1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 113

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 13
Mondo ID	MONDO:0013924
OMIM	614856
DOID	DOID:0110342
UMLS	C3553887
MedGen	766801
GARD	0015856
Is cancer (heuristic)	no

Also known as: BMP1 osteogenesis imperfecta · OI13 · osteogenesis imperfecta caused by mutation in BMP1 · osteogenesis imperfecta, type XIII

Data availability: 113 ClinVar variants · 3 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 › osteogenesis imperfecta › osteogenesis imperfecta type 13

Related subtypes (9): brittle bone disorder, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, high bone mass osteogenesis imperfecta, osteogenesis imperfecta, IIA 22, osteogenesis imperfecta, type 21, osteogenesis imperfecta, type 20, COL1A2-related osteogenesis imperfecta, osteogenesis imperfecta and a reduction of bone mineral density., osteogenesis imperfecta, type 23

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

113 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 25 conflicting classifications of pathogenicity, 14 benign, 10 benign/likely benign, 7 likely pathogenic, 7 pathogenic, 7 likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299300	NM_006129.5(BMP1):c.584dup (p.Gln197fs)	BMP1	Pathogenic	criteria provided, multiple submitters, no conflicts
190231	NM_006129.5(BMP1):c.2108-359T>C	BMP1	Pathogenic	no assertion criteria provided
190232	NM_006129.5(BMP1):c.2107G>C (p.Asp703His)	BMP1	Pathogenic	no assertion criteria provided
190233	NM_006129.5(BMP1):c.808A>G (p.Met270Val)	BMP1	Pathogenic	no assertion criteria provided
190234	NM_006129.5(BMP1):c.1297G>T (p.Ala433Ser)	BMP1	Pathogenic	criteria provided, single submitter
2735141	NM_001199.4(BMP1):c.2188dup (p.Gln730fs)	BMP1	Pathogenic	criteria provided, multiple submitters, no conflicts
3003541	NM_006129.5(BMP1):c.549C>A (p.Cys183Ter)	BMP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37307	NM_006129.5(BMP1):c.34G>C (p.Gly12Arg)	BMP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4082206	NM_006129.5(BMP1):c.835A>G (p.Arg279Gly)	BMP1	Pathogenic	criteria provided, single submitter
1236182	NM_001199.4(BMP1):c.2191T>C (p.Ter731Arg)	BMP1	Likely pathogenic	criteria provided, single submitter
1299299	NM_006129.5(BMP1):c.965G>A (p.Cys322Tyr)	BMP1	Likely pathogenic	criteria provided, single submitter
3595462	NM_006129.5(BMP1):c.1130dup (p.Tyr377Ter)	BMP1	Likely pathogenic	criteria provided, single submitter
3595463	NM_006129.5(BMP1):c.2029C>T (p.Gln677Ter)	BMP1	Likely pathogenic	criteria provided, single submitter
3595464	NM_006129.5(BMP1):c.2288G>A (p.Trp763Ter)	BMP1	Likely pathogenic	criteria provided, single submitter
37306	NM_006129.5(BMP1):c.747C>G (p.Phe249Leu)	BMP1	Likely pathogenic	criteria provided, single submitter
4819338	NM_006129.5(BMP1):c.1926+2dup	BMP1	Likely pathogenic	criteria provided, single submitter
1033073	NM_006129.5(BMP1):c.962-18C>G	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2207884	NM_006129.5(BMP1):c.2569G>A (p.Ala857Thr)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2885627	NM_006129.5(BMP1):c.2424C>T (p.Phe808=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362577	NM_006129.5(BMP1):c.402C>T (p.Val134=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362585	NM_006129.5(BMP1):c.1623C>T (p.Ala541=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362594	NM_006129.5(BMP1):c.2406C>T (p.Tyr802=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362596	NM_006129.5(BMP1):c.2430G>T (p.Gly810=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362597	NM_006129.5(BMP1):c.2445C>T (p.Ala815=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362604	NM_006129.5(BMP1):c.2724C>T (p.Thr908=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
498501	NM_006129.5(BMP1):c.2134G>A (p.Gly712Ser)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
748146	NM_006129.5(BMP1):c.2847G>A (p.Ser949=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
764850	NM_006129.5(BMP1):c.2700C>T (p.Tyr900=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
793400	NM_006129.5(BMP1):c.2487C>A (p.Pro829=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
799728	NM_006129.5(BMP1):c.1938C>T (p.Tyr646=)	BMP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
BMP1	Strong	Autosomal recessive	osteogenesis imperfecta type 13	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMP1	Orphanet:216812	Osteogenesis imperfecta type 3
BMP1	Orphanet:314029	High bone mass osteogenesis imperfecta

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
BMP1	HGNC:1067	ENSG00000168487	P13497	Bone morphogenetic protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP1	Bone morphogenetic protein 1	Metalloprotease that plays key roles in regulating the formation of the extracellular matrix (ECM) via processing of various precursor proteins into mature functional enzymes or structural proteins.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMP1	Protease	yes	2.7.11.4	EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_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
left uterine tube	1
right adrenal gland cortex	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP1	236	ubiquitous	marker	stromal cell of endometrium, left uterine tube, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMP1	2,003

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMP1	P13497	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
HDL assembly	1	1427.5×	0.004	BMP1
Anchoring fibril formation	1	761.3×	0.004	BMP1
Crosslinking of collagen fibrils	1	571.0×	0.004	BMP1
Collagen formation	1	456.8×	0.004	BMP1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.008	BMP1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.008	BMP1
Degradation of the extracellular matrix	1	117.7×	0.010	BMP1
Extracellular matrix organization	1	63.1×	0.016	BMP1

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
positive regulation of cartilage development	1	936.2×	0.006	BMP1
cartilage condensation	1	766.0×	0.006	BMP1
dorsal/ventral pattern formation	1	421.3×	0.007	BMP1
ossification	1	227.7×	0.008	BMP1
collagen fibril organization	1	224.7×	0.008	BMP1
protein processing	1	170.2×	0.009	BMP1
skeletal system development	1	125.8×	0.010	BMP1
proteolysis	1	34.2×	0.033	BMP1
cell differentiation	1	29.1×	0.034	BMP1

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
BMP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BMP1	30	Binding:29, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMP1	2.7.11.4, 3.4.24.19, 3.4.24.21	[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase, procollagen C-endopeptidase, astacin

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	1	BMP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
BMP1	30	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.