BMP3
protein-codingbone morphogenetic protein 3, the group of Bone morphogenetic proteins
Gene summary
This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein suppresses osteoblast differentiation, and negatively regulates bone density, by modulating TGF-beta receptor availability to other ligands. [provided by RefSeq, Jul 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0001476
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BMP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001201.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 71 | 3 | 3 | 77 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 71 | 3 | 3 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001192.4 | 3 | MANE Select | |
| Ensembl | ENSP00000282701.2 | 3 | MANE Select | |
| Ensembl | ENSP00000579168.1 | 3 | Standard | |
| Ensembl | ENSP00000579168.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| bmp3 | Danio rerio | Structure: neurocranium Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adipogenesis
- GPCR signaling-G alpha q
- GPCR signaling-cholera toxin
- GPCR signaling-pertussis toxin
- TGF-beta super family signaling pathway canonical
Biological Process
- skeletal system development
- osteoblast differentiation
- cell-cell signaling
- regulation of signaling receptor activity
- positive regulation of pathway-restricted SMAD protein phosphorylation
Molecular Function
- signaling receptor binding
- cytokine activity
- transforming growth factor beta receptor binding
- growth factor activity
- BMP receptor binding
Cellular Component
- extracellular space
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000282701
- Coding exons
- 3
- Length
- 26567
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0659 | 253 | 256 | 0.988 | 0.0000125 | 3052 |
| Missense (PolyPhen) | 99 | 100.09 | 0.98915 | 1286 | ||
| Synonymous | -0.725 | 111 | 102 | 1.09 | 0.00000509 | 944 |
| Loss of Function | 2.56 | 5 | 16.1 | 0.311 | 7.44e-7 | 205 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000062 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negatively regulates bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentitation and ossification. {ECO:0000269|PubMed:11138004, ECO:0000269|PubMed:15269709}.;
Recessive Scores
- pRec
- 0.203
Intolerance Scores
- LoFtool
- 0.266
- RVIS EVS
- 1.07
- RVIS percentile EVS
- 91.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |