BMP1

bone morphogenetic protein 1, the group of Astacins|Bone morphogenetic proteins

Basic information

Region (hg38): 8:22165140-22212326

Previous symbols: [ "PCOLC" ]

Links

ENSG00000168487 ∙ NCBI:649 ∙ OMIM:112264 ∙ HGNC:1067 ∙ Uniprot:P13497 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 13 (Moderate), mode of inheritance: AR
• osteogenesis imperfecta type 13 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
• high bone mass osteogenesis imperfecta (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XIII	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Ophthalmologic	22052668; 22482805
The use of bisphosphonates has been described, but it is unclear if an early (genetic) diagnosis would be advantageous

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BMP1 gene.

• not provided (15 variants)
• Osteogenesis imperfecta type 13 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMP1 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			2	310	7	319
missense	1	3	186	15	3	208
nonsense	6	1				7
start loss	2					2
frameshift	7	1	1			9
inframe indel						0
splice donor/acceptor (+/-2bp)		7	1			8
splice region		2	7	38		47
non coding			12	198	52	262
Total	16	12	202	523	62

Highest pathogenic variant AF is 0.0000268

Variants in BMP1

This is a list of pathogenic ClinVar variants found in the BMP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-22165142-CGGAG-C		Osteogenesis Imperfecta, Recessive	Conflicting classifications of pathogenicity (Oct 23, 2019)
8-22165236-A-G		Osteogenesis Imperfecta, Recessive • Interstitial lung disease 2 • Pulmonary Surfactant Metabolism Dysfunction, Dominant	Benign (Jun 14, 2018)
8-22165280-G-A		Surfactant metabolism dysfunction, pulmonary, 2 • Interstitial lung disease 2 • Osteogenesis Imperfecta, Recessive	Uncertain significance (Jan 13, 2018)
8-22165391-C-G		Osteogenesis Imperfecta, Recessive • Interstitial lung disease 2 • Pulmonary Surfactant Metabolism Dysfunction, Dominant • not specified • Osteogenesis imperfecta type 13	Benign/Likely benign (Jan 13, 2018)
8-22165406-A-G			Pathogenic (Oct 12, 2023)
8-22165407-T-C			Pathogenic (Oct 27, 2022)
8-22165411-C-G			Likely benign (Dec 23, 2023)
8-22165412-G-C			Uncertain significance (Oct 18, 2022)
8-22165414-C-T			Likely benign (Apr 19, 2023)
8-22165422-G-T		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
8-22165426-G-C			Likely benign (Nov 22, 2023)
8-22165428-C-G		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
8-22165435-G-A			Likely benign (May 01, 2023)
8-22165438-C-T			Benign/Likely benign (Jan 26, 2024)
8-22165439-G-C		Osteogenesis imperfecta type 13 • Abnormality of the skeletal system • Osteogenesis imperfecta	Pathogenic/Likely pathogenic (May 14, 2024)
8-22165441-G-A			Likely benign (Sep 30, 2023)
8-22165441-G-T			Likely benign (Dec 03, 2023)
8-22165453-C-A			Likely benign (Dec 21, 2022)
8-22165454-C-T		Osteogenesis imperfecta	Uncertain significance (May 01, 2020)
8-22165456-G-T			Likely benign (Aug 28, 2023)
8-22165462-C-G			Likely benign (May 19, 2023)
8-22165465-C-A			Likely benign (Dec 10, 2023)
8-22165466-C-A			Likely benign (Oct 18, 2023)
8-22165483-C-G			Likely benign (Oct 22, 2023)
8-22165483-C-T			Likely benign (Oct 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BMP1	protein_coding	protein_coding	ENST00000306385	20	47591

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000886	0.999	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.99	512	655	0.782	0.0000437	6505
Missense in Polyphen		136	226.14	0.60139		2117
Synonymous	-0.281	274	268	1.02	0.0000198	1862
Loss of Function	4.74	16	53.3	0.300	0.00000287	560

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000417	0.000416
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000159	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000660	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves the C-terminal propeptides of procollagen I, II and III. Induces cartilage and bone formation. May participate in dorsoventral patterning during early development by cleaving chordin (CHRD). Responsible for the proteolytic activation of lysyl oxidase LOX.
• Disease: DISEASE: Osteogenesis imperfecta 13 (OI13) [MIM:614856]: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI13 is characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, severe bone deformity, and recurrent fractures affecting both upper and lower limbs. {ECO:0000269|PubMed:22052668, ECO:0000269|PubMed:22482805, ECO:0000269|PubMed:25402547}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adipogenesis;Cardiac Progenitor Differentiation;Canonical and Non-Canonical TGF-B signaling;EDA Signalling in Hair Follicle Development;Crosslinking of collagen fibrils;Assembly of collagen fibrils and other multimeric structures;HDL assembly;Plasma lipoprotein assembly;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;DroToll-like;Transport of small molecules;Anchoring fibril formation;Degradation of the extracellular matrix;Plasma lipoprotein assembly, remodeling, and clearance (Consensus)

Recessive Scores

• pRec: 0.475

Intolerance Scores

• loftool: 0.687
• rvis_EVS: -1.96
• rvis_percentile_EVS: 1.84

Haploinsufficiency Scores

• pHI: 0.750
• hipred: Y
• hipred_score: 0.563
• ghis: 0.646

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bmp1
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; muscle phenotype; 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); 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); hematopoietic system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: bmp1a
• Affected structure: osteoblast
• Phenotype tag: abnormal
• Phenotype quality: cuboid

Gene ontology

• Biological process: skeletal system development;cartilage condensation;ossification;proteolysis;multicellular organism development;regulation of signaling receptor activity;extracellular matrix disassembly;cell differentiation;high-density lipoprotein particle assembly;positive regulation of cartilage development
• Cellular component: extracellular region;extracellular space;Golgi apparatus;vesicle
• Molecular function: metalloendopeptidase activity;serine-type endopeptidase activity;cytokine activity;calcium ion binding;protein binding;growth factor activity;peptidase activity;metallopeptidase activity;zinc ion binding;identical protein binding