Menu
GeneBe

BMP1

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

Basic information

Region (hg38): 8:22165139-22212326

Previous symbols: [ "PCOLC" ]

Links

ENSG00000168487NCBI:649OMIM:112264HGNC:1067Uniprot:P13497AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Osteogenesis imperfecta, type XIIIARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Ophthalmologic22052668; 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 (459 variants)
  • Osteogenesis imperfecta type 13 (95 variants)
  • Inborn genetic diseases (43 variants)
  • Osteogenesis imperfecta (26 variants)
  • not specified (20 variants)
  • Osteogenesis Imperfecta, Recessive (3 variants)
  • BMP1-related condition (3 variants)
  • Interstitial lung disease 2 (3 variants)
  • Pulmonary Surfactant Metabolism Dysfunction, Dominant (2 variants)
  • Osteogenesis imperfecta type III (2 variants)
  • Abnormality of the skeletal system (1 variants)
  • Surfactant metabolism dysfunction, pulmonary, 2 (1 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
4
clinvar
104
clinvar
6
clinvar
114
missense
1
clinvar
3
clinvar
167
clinvar
10
clinvar
3
clinvar
184
nonsense
1
clinvar
1
clinvar
2
start loss
1
clinvar
1
frameshift
3
clinvar
1
clinvar
1
clinvar
5
inframe indel
0
splice donor/acceptor (+/-2bp)
5
clinvar
1
clinvar
6
splice region
1
8
18
1
28
non coding
13
clinvar
105
clinvar
48
clinvar
166
Total 6 10 186 219 57

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)362572
8-22165236-A-G Osteogenesis Imperfecta, Recessive • Interstitial lung disease 2 • Pulmonary Surfactant Metabolism Dysfunction, Dominant Benign (Jun 14, 2018)362573
8-22165280-G-A Surfactant metabolism dysfunction, pulmonary, 2 • Interstitial lung disease 2 • Osteogenesis Imperfecta, Recessive Uncertain significance (Jan 13, 2018)362574
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)362575
8-22165406-A-G Pathogenic (Oct 12, 2023)2987540
8-22165407-T-C Pathogenic (Oct 27, 2022)1433797
8-22165411-C-G Likely benign (Dec 23, 2023)2807564
8-22165412-G-C Uncertain significance (Oct 18, 2022)2070218
8-22165414-C-T Likely benign (Apr 19, 2023)2091830
8-22165426-G-C Likely benign (Nov 22, 2023)2980022
8-22165428-C-G Inborn genetic diseases Uncertain significance (Jan 02, 2024)1478749
8-22165435-G-A Likely benign (May 01, 2023)2860285
8-22165438-C-T Benign/Likely benign (Jan 26, 2024)512914
8-22165439-G-C Osteogenesis imperfecta type 13 • Abnormality of the skeletal system Pathogenic/Likely pathogenic (Jun 17, 2023)37307
8-22165441-G-A Likely benign (Sep 30, 2023)2889505
8-22165441-G-T Likely benign (Dec 03, 2023)3005374
8-22165453-C-A Likely benign (Dec 21, 2022)2822935
8-22165454-C-T Osteogenesis imperfecta Uncertain significance (May 01, 2020)1702087
8-22165456-G-T Likely benign (Aug 28, 2023)2755299
8-22165462-C-G Likely benign (May 19, 2023)1638515
8-22165465-C-A Likely benign (Dec 10, 2023)2993724
8-22165466-C-A Likely benign (Oct 18, 2023)2892224
8-22165483-C-G Likely benign (Oct 22, 2023)2807837
8-22165483-C-T Likely benign (Oct 15, 2023)2779669
8-22165491-C-A Inborn genetic diseases Uncertain significance (Jun 24, 2022)1506549

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BMP1protein_codingprotein_codingENST00000306385 2047591
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0008860.9991257120361257480.000143
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.995126550.7820.00004376505
Missense in Polyphen136226.140.601392117
Synonymous-0.2812742681.020.00001981862
Loss of Function4.741653.30.3000.00000287560

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004170.000416
Ashkenazi Jewish0.0001000.0000992
East Asian0.00005440.0000544
Finnish0.0001860.000185
European (Non-Finnish)0.0001590.000149
Middle Eastern0.00005440.0000544
South Asian0.00006600.0000653
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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