BMPR1B
bone morphogenetic protein receptor type 1B, the group of CD molecules|Type 1 receptor serine/threonine kinases
Basic information
Region (hg38): 4:94757955-95158448
Links
Phenotypes
GenCC
Source:
- brachydactyly type A2 (Definitive), mode of inheritance: AR
- brachydactyly type A1D (Moderate), mode of inheritance: AD
- acromesomelic dysplasia 3 (Moderate), mode of inheritance: AR
- acromesomelic dysplasia 2A (Supportive), mode of inheritance: AR
- acromesomelic dysplasia 2B (Supportive), mode of inheritance: AR
- brachydactyly type A1 (Supportive), mode of inheritance: AD
- brachydactyly type A2 (Supportive), mode of inheritance: AD
- acromesomelic dysplasia 3 (Strong), mode of inheritance: AR
- brachydactyly type A2 (Strong), mode of inheritance: AD
- pulmonary arterial hypertension (Disputed Evidence), mode of inheritance: Unknown
- brachydactyly (Moderate), mode of inheritance: AD
- acromesomelic dysplasia 3 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Acromesomelic dysplasia 3; Brachydactyly, type A1, D; Brachydactyly, type A2; Brachydactyly C/Symphalangism-like phenotype | AD/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 | Genitourinary; Musculoskeletal | 14523231; 15805157; 16957682; 24129431; 25758993; 26105076 |
| In Acromesomelic dysplasia, Demirhan type, interventions may be beneficial to allow reproductive capacity |
ClinVar
This is a list of variants' phenotypes submitted to
- Acromesomelic_dysplasia_3 (212 variants)
- Type_A2_brachydactyly (207 variants)
- Inborn_genetic_diseases (53 variants)
- not_provided (46 variants)
- Brachydactyly (30 variants)
- BMPR1B-related_disorder (17 variants)
- Brachydactyly_type_A1D (7 variants)
- Pulmonary_arterial_hypertension (2 variants)
- not_specified (2 variants)
- Premature_ovarian_insufficiency (1 variants)
- Idiopathic_pulmonary_arterial_hypertension (1 variants)
- Pulmonary_hypertension,_primary,_3 (1 variants)
- Acromesomelic_dysplasia_2C,_Hunter-Thompson_type (1 variants)
- Acromesomelic_dysplasia_2B (1 variants)
- Pulmonary_arterial_hypertension_associated_with_congenital_heart_disease (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMPR1B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001203.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 42 | 47 | ||||
| missense | 136 | 32 | 183 | |||
| nonsense | 3 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 10 | 6 | 138 | 75 | 9 |
Highest pathogenic variant AF is 0.000013147688
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BMPR1B | protein_coding | protein_coding | ENST00000440890 | 11 | 400481 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00137 | 125726 | 0 | 7 | 125733 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.270 | 278 | 291 | 0.955 | 0.0000148 | 3490 |
| Missense in Polyphen | 115 | 141.81 | 0.81096 | 1653 | ||
| Synonymous | -0.679 | 108 | 99.4 | 1.09 | 0.00000486 | 999 |
| Loss of Function | 4.55 | 2 | 28.0 | 0.0714 | 0.00000145 | 337 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000905 | 0.0000905 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000943 | 0.0000924 |
| European (Non-Finnish) | 0.00000884 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP7/OP-1 and GDF5. Positively regulates chondrocyte differentiation through GDF5 interaction. {ECO:0000250|UniProtKB:P36898}.;
- Disease
- DISEASE: Acromesomelic dysplasia, Demirhan type (AMDD) [MIM:609441]: A form of chondrodysplasia. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDD inheritance is autosomal recessive. {ECO:0000269|PubMed:15805157, ECO:0000269|PubMed:24129431, ECO:0000269|PubMed:26105076}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly A2 (BDA2) [MIM:112600]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially. {ECO:0000269|PubMed:14523231, ECO:0000269|PubMed:16957682}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly A1, D (BDA1D) [MIM:616849]: A form of brachydactyly type A1. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1D inheritance is autosomal dominant. {ECO:0000269|PubMed:25758993}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- TGF-beta signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);TGF-Core;Bone Morphogenic Protein (BMP) Signalling and Regulation;Ovarian Infertility Genes;ESC Pluripotency Pathways;Signal Transduction;BMP2 signaling TAK1;TGF-beta super family signaling pathway canonical;IL-7 signaling;BMP receptor signaling;BMP Signalling Pathway;JAK STAT pathway and regulation;EPO signaling;BMP2 signaling TGF-beta MV;VEGF;Signaling by BMP;Signaling by TGF-beta family members;BMP signaling Dro
(Consensus)
Recessive Scores
- pRec
- 0.339
Intolerance Scores
- loftool
- 0.100
- rvis_EVS
- -0.76
- rvis_percentile_EVS
- 13.45
Haploinsufficiency Scores
- pHI
- 0.895
- hipred
- Y
- hipred_score
- 0.853
- ghis
- 0.582
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bmpr1b
- Phenotype
- growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; craniofacial phenotype; vision/eye 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); normal phenotype; reproductive system phenotype; pigmentation phenotype; embryo phenotype; skeleton 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;
Zebrafish Information Network
- Gene name
- bmpr1ba
- Affected structure
- skeletal muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- differentiated
Gene ontology
- Biological process
- skeletal system development;cartilage condensation;ovarian cumulus expansion;eye development;chondrocyte development;protein phosphorylation;inflammatory response;transforming growth factor beta receptor signaling pathway;pattern specification process;dorsal/ventral pattern formation;proteoglycan biosynthetic process;positive regulation of bone mineralization;BMP signaling pathway;retinal ganglion cell axon guidance;positive regulation of chondrocyte differentiation;limb morphogenesis;ovulation cycle;positive regulation of cell differentiation;positive regulation of osteoblast differentiation;positive regulation of transcription by RNA polymerase II;retina development in camera-type eye;endochondral bone morphogenesis;positive regulation of cartilage development;cellular response to BMP stimulus;positive regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of chondrocyte proliferation
- Cellular component
- plasma membrane;integral component of plasma membrane;dendrite;neuronal cell body;receptor complex;HFE-transferrin receptor complex
- Molecular function
- protein serine/threonine kinase activity;transmembrane receptor protein serine/threonine kinase activity;transforming growth factor beta-activated receptor activity;transforming growth factor beta receptor activity, type I;protein binding;ATP binding;growth factor binding;SMAD binding;metal ion binding