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GeneBe

BMP2

bone morphogenetic protein 2, the group of Bone morphogenetic proteins

Basic information

Region (hg38): 20:6767685-6780246

Previous symbols: [ "BMP2A" ]

Links

ENSG00000125845NCBI:650OMIM:112261HGNC:1069Uniprot:P12643AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • brachydactyly type A2 (Supportive), mode of inheritance: AD
  • brachydactyly type A2 (Limited), mode of inheritance: Unknown
  • short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1ADCardiovascularAmong other features, the condition can involve arrhythmias, and awareness can allow early diagnosis and managementCardiovascular; Craniofacial; Musculoskeletal7390514; 19327734; 21357617; 29198724
Brachydactyly, type A2 involves duplication of a downstream regulatory element of the gene

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BMP2 gene.

  • not provided (116 variants)
  • Inborn genetic diseases (14 variants)
  • Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (7 variants)
  • Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 (7 variants)
  • not specified (6 variants)
  • Ventricular septal defect 1 (1 variants)
  • Brachydactyly type A2 (1 variants)
  • BMP2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
30
clinvar
2
clinvar
33
missense
63
clinvar
4
clinvar
2
clinvar
69
nonsense
7
clinvar
4
clinvar
11
start loss
1
clinvar
1
frameshift
2
clinvar
3
clinvar
1
clinvar
6
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
1
1
non coding
4
clinvar
4
Total 10 7 67 34 8

Variants in BMP2

This is a list of pathogenic ClinVar variants found in the BMP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
20-6770118-AG-CC Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 Pathogenic (Feb 15, 2021)492936
20-6770127-A-G Uncertain significance (Dec 12, 2017)489195
20-6770142-C-T Type A2 brachydactyly • Inborn genetic diseases Uncertain significance (Feb 05, 2024)850711
20-6770169-C-T Pathogenic (Jun 05, 2018)620208
20-6770174-C-G Likely benign (Aug 05, 2020)1100541
20-6770183-CGGCG-C Pathogenic (Aug 24, 2021)1073026
20-6770190-G-A Uncertain significance (Aug 21, 2023)2781045
20-6770194-G-C Uncertain significance (Aug 15, 2022)1506168
20-6770198-C-T BMP2-related condition Likely benign (Mar 27, 2019)3047413
20-6770205-G-T Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies • Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 Likely pathogenic (Oct 15, 2018)492934
20-6770213-C-A Likely benign (Aug 04, 2023)1674924
20-6770213-C-T BMP2-related condition Conflicting classifications of pathogenicity (Jun 02, 2022)1801895
20-6770216-C-A Likely benign (Dec 04, 2021)1660062
20-6770226-G-C Uncertain significance (Aug 12, 2022)2421743
20-6770225-C-CGCG Uncertain significance (Oct 28, 2022)1938652
20-6770233-C-T Uncertain significance (Oct 23, 2022)1920753
20-6770235-T-G not specified • Ventricular septal defect 1 Benign (Jan 30, 2024)195137
20-6770256-C-G Inborn genetic diseases Uncertain significance (May 03, 2023)2542837
20-6770259-C-A Uncertain significance (Sep 10, 2023)2852875
20-6770262-T-A Inborn genetic diseases Uncertain significance (Jan 05, 2024)2361086
20-6770268-G-T Pathogenic (Jun 27, 2022)1451444
20-6770270-G-C Uncertain significance (Sep 24, 2021)1419739
20-6770276-G-C Likely benign (Jun 20, 2022)1609097
20-6770285-C-G Uncertain significance (Dec 25, 2021)1348330
20-6770298-C-T Uncertain significance (Sep 30, 2021)1396590

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BMP2protein_codingprotein_codingENST00000378827 212617
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9880.012000000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.141882370.7920.00001282586
Missense in Polyphen78137.080.569021520
Synonymous-0.49710497.81.060.00000567793
Loss of Function3.38013.30.007.39e-7148

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Induces cartilage and bone formation (PubMed:3201241). Stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- ATF4 pathway. BMP2 activation of EIF2AK3 stimulates phosphorylation of EIF2A which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. In addition stimulates TMEM119, which upregulates the expression of ATF4 (PubMed:24362451). {ECO:0000269|PubMed:24362451, ECO:0000269|PubMed:3201241}.;
Disease
DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (SSFSC) [MIM:617877]: An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract. {ECO:0000269|PubMed:29198724}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
TGF-beta signaling pathway - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);TGF-Core;Bone Morphogenic Protein (BMP) Signalling and Regulation;Heart Development;Adipogenesis;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Differentiation of white and brown adipocyte;Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway;BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation;Senescence and Autophagy in Cancer;Transcriptional regulation by RUNX2;Signal Transduction;Gene expression (Transcription);alk in cardiac myocytes;Generic Transcription Pathway;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;RNA Polymerase II Transcription;Extracellular matrix organization;BMP2 signaling TAK1;Molecules associated with elastic fibres;Elastic fibre formation;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;BMP receptor signaling;BMP Signalling Pathway;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;Signaling by BMP;Signaling by TGF-beta family members;BMP signaling Dro;Regulation of RUNX2 expression and activity (Consensus)

Recessive Scores

pRec
0.775

Intolerance Scores

loftool
rvis_EVS
-0.27
rvis_percentile_EVS
34.6

Haploinsufficiency Scores

pHI
1.00
hipred
Y
hipred_score
0.875
ghis
0.535

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.937

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Bmp2
Phenotype
growth/size/body region phenotype; craniofacial phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; embryo phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype;

Zebrafish Information Network

Gene name
bmp2b
Affected structure
erythroid lineage cell
Phenotype tag
abnormal
Phenotype quality
absent

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;activation of MAPK activity;skeletal system development;osteoblast differentiation;branching involved in ureteric bud morphogenesis;response to hypoxia;in utero embryonic development;epithelial to mesenchymal transition;positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;chondrocyte differentiation;BMP signaling pathway involved in heart induction;atrioventricular valve morphogenesis;endocardial cushion morphogenesis;negative regulation of Wnt signaling pathway involved in heart development;proteoglycan metabolic process;regulation of transcription, DNA-templated;protein phosphorylation;inflammatory response;Notch signaling pathway;cell-cell signaling;heart development;negative regulation of cell population proliferation;response to bacterium;animal organ morphogenesis;regulation of signaling receptor activity;positive regulation of gene expression;negative regulation of gene expression;positive regulation of epithelial to mesenchymal transition;positive regulation of pathway-restricted SMAD protein phosphorylation;negative regulation of steroid biosynthetic process;positive regulation of phosphatase activity;telencephalon development;telencephalon regionalization;positive regulation of Wnt signaling pathway;bone mineralization;positive regulation of cell migration;positive regulation of bone mineralization;BMP signaling pathway;protein destabilization;positive regulation of protein binding;negative regulation of aldosterone biosynthetic process;positive regulation of osteoblast proliferation;cardiocyte differentiation;embryonic heart tube anterior/posterior pattern specification;bone mineralization involved in bone maturation;odontogenesis of dentin-containing tooth;positive regulation of odontogenesis;regulation of odontogenesis of dentin-containing tooth;regulation of apoptotic process;positive regulation of apoptotic process;regulation of MAPK cascade;positive regulation of MAPK cascade;negative regulation of insulin-like growth factor receptor signaling pathway;cell fate commitment;positive regulation of fat cell differentiation;positive regulation of neuron differentiation;positive regulation of osteoblast differentiation;positive regulation of ossification;negative regulation of cell cycle;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell development;positive regulation of astrocyte differentiation;mesenchymal cell differentiation;inner ear development;negative regulation of calcium-independent cell-cell adhesion;cardiac muscle cell differentiation;cardiac muscle tissue morphogenesis;oxidation-reduction process;pericardium development;corticotropin hormone secreting cell differentiation;thyroid-stimulating hormone-secreting cell differentiation;cardiac epithelial to mesenchymal transition;pathway-restricted SMAD protein phosphorylation;SMAD protein signal transduction;mesenchyme development;positive regulation of Wnt signaling pathway by BMP signaling pathway;positive regulation of cartilage development;positive regulation of ERK1 and ERK2 cascade;cellular response to organic cyclic compound;cellular response to BMP stimulus;mesenchymal cell proliferation involved in ureteric bud development;negative regulation of canonical Wnt signaling pathway;positive regulation of p38MAPK cascade;positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus;positive regulation of pri-miRNA transcription by RNA polymerase II;negative regulation of cortisol biosynthetic process;negative regulation of cardiac muscle cell differentiation
Cellular component
extracellular region;extracellular space;cell surface;intracellular membrane-bounded organelle;BMP receptor complex
Molecular function
retinol dehydrogenase activity;signaling receptor binding;cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity;phosphatase activator activity;co-receptor binding;SMAD binding;protein heterodimerization activity;BMP receptor binding