BMP2

bone morphogenetic protein 2, the group of Bone morphogenetic proteins

Basic information

Region (hg38): 20:6767685-6780246

Previous symbols: [ "BMP2A" ]

Links

ENSG00000125845 ∙ NCBI:650 ∙ OMIM:112261 ∙ HGNC:1069 ∙ Uniprot:P12643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1	AD	Cardiovascular	Among other features, the condition can involve arrhythmias, and awareness can allow early diagnosis and management	Cardiovascular; Craniofacial; Musculoskeletal	7390514; 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	30	2	33
missense			63	4	2	69
nonsense	7	4				11
start loss			1			1
frameshift	2	3	1			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1					1
splice region			1			1
non coding					4	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)
20-6770127-A-G			Uncertain significance (Dec 12, 2017)
20-6770142-C-T		Type A2 brachydactyly • Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
20-6770169-C-T			Pathogenic (Jun 05, 2018)
20-6770174-C-G			Likely benign (Aug 05, 2020)
20-6770183-CGGCG-C			Pathogenic (Aug 24, 2021)
20-6770190-G-A			Uncertain significance (Aug 21, 2023)
20-6770194-G-C			Uncertain significance (Aug 15, 2022)
20-6770198-C-T		BMP2-related disorder	Likely benign (Mar 27, 2019)
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)
20-6770213-C-A			Likely benign (Aug 04, 2023)
20-6770213-C-T		BMP2-related disorder	Conflicting classifications of pathogenicity (Jun 02, 2022)
20-6770216-C-A			Likely benign (Dec 04, 2021)
20-6770226-G-C			Uncertain significance (Aug 12, 2022)
20-6770225-C-CGCG			Uncertain significance (Oct 28, 2022)
20-6770233-C-T			Uncertain significance (Oct 23, 2022)
20-6770235-T-G		not specified • Ventricular septal defect 1	Benign (Jan 30, 2024)
20-6770256-C-G		Inborn genetic diseases	Uncertain significance (May 03, 2023)
20-6770259-C-A			Uncertain significance (Sep 10, 2023)
20-6770262-T-A		Inborn genetic diseases	Uncertain significance (Jan 05, 2024)
20-6770268-G-T			Pathogenic (Jun 27, 2022)
20-6770270-G-C			Uncertain significance (Sep 24, 2021)
20-6770276-G-C			Likely benign (Jun 20, 2022)
20-6770285-C-G			Uncertain significance (Dec 25, 2021)
20-6770298-C-T			Uncertain significance (Sep 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BMP2	protein_coding	protein_coding	ENST00000378827	2	12617

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0120	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	188	237	0.792	0.0000128	2586
Missense in Polyphen		78	137.08	0.56902		1520
Synonymous	-0.497	104	97.8	1.06	0.00000567	793
Loss of Function	3.38	0	13.3	0.00	7.39e-7	148

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

• 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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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