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BMPR1B

bone morphogenetic protein receptor type 1B, the group of CD molecules|Type 1 receptor serine/threonine kinases

Basic information

Region (hg38): 4:94757954-95158448

Links

ENSG00000138696NCBI:658OMIM:603248HGNC:1077Uniprot:O00238AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Acromesomelic dysplasia 3; Brachydactyly, type A1, D; Brachydactyly, type A2; Brachydactyly C/Symphalangism-like phenotypeAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingGenitourinary; Musculoskeletal14523231; 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 ClinVar and linked to the BMPR1B gene.

  • Brachydactyly (123 variants)
  • Brachydactyly type A2;Acromesomelic dysplasia 3 (85 variants)
  • not provided (62 variants)
  • Acromesomelic dysplasia 3;Brachydactyly type A2 (42 variants)
  • Inborn genetic diseases (23 variants)
  • Acromesomelic dysplasia 3 (6 variants)
  • BMPR1B-related condition (4 variants)
  • Brachydactyly type A2 (3 variants)
  • not specified (3 variants)
  • Idiopathic pulmonary arterial hypertension (1 variants)
  • Pulmonary hypertension, primary, 3 (1 variants)
  • Brachydactyly type A2;Brachydactyly type A1D (1 variants)
  • Acromesomelic dysplasia 3;Brachydactyly type A1D;Brachydactyly type A2 (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.

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
29
clinvar
3
clinvar
33
missense
1
clinvar
3
clinvar
79
clinvar
17
clinvar
6
clinvar
106
nonsense
0
start loss
0
frameshift
0
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
2
3
1
6
non coding
55
clinvar
24
clinvar
57
clinvar
136
Total 1 4 135 71 66

Highest pathogenic variant AF is 0.0000131

Variants in BMPR1B

This is a list of pathogenic ClinVar variants found in the BMPR1B region.

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

Position Type Phenotype Significance ClinVar
4-94757964-C-G Brachydactyly Uncertain significance (Jan 13, 2018)904995
4-94758053-G-C Brachydactyly Uncertain significance (Jan 13, 2018)904996
4-94875831-G-A Brachydactyly Uncertain significance (Jan 12, 2018)904997
4-94875846-A-G Brachydactyly Uncertain significance (Mar 02, 2018)904998
4-94875884-A-G Brachydactyly Benign (Jan 12, 2018)906578
4-94875896-T-C Brachydactyly • BMPR1B-related condition Benign (Sep 16, 2019)906579
4-94996064-C-G Brachydactyly Uncertain significance (Feb 09, 2018)906580
4-94996135-G-T Brachydactyly Likely benign (Oct 02, 2017)906581
4-95051389-G-A Likely benign (Feb 13, 2020)1208314
4-95051585-C-T Acromesomelic dysplasia 3 Uncertain significance (-)2504599
4-95051729-G-A BMPR1B-related condition Likely benign (Nov 25, 2019)3055277
4-95051734-A-G BMPR1B-related condition Benign (Jul 29, 2019)3035814
4-95051768-A-G BMPR1B-related condition Likely benign (Mar 16, 2019)3050330
4-95051944-GCTTT-G Benign (Jun 25, 2021)1302826
4-95051945-C-T Likely benign (Jul 18, 2020)1213412
4-95052055-A-T Benign (Nov 10, 2018)1175514
4-95104151-T-G Benign (Sep 04, 2018)1246297
4-95104271-A-G Likely benign (Mar 14, 2020)1202241
4-95104435-G-A Brachydactyly • Type A2 brachydactyly;Acromesomelic dysplasia 3 • Acromesomelic dysplasia 3 • Idiopathic pulmonary arterial hypertension Conflicting classifications of pathogenicity (Jan 22, 2024)906582
4-95104439-T-G Type A2 brachydactyly;Acromesomelic dysplasia 3 Likely benign (Jul 12, 2022)1405714
4-95104440-G-A Acromesomelic dysplasia 3;Type A2 brachydactyly • Inborn genetic diseases Conflicting classifications of pathogenicity (May 15, 2023)1043555
4-95104442-A-G Type A2 brachydactyly;Acromesomelic dysplasia 3 Likely benign (Jan 02, 2024)1126554
4-95104445-A-G Type A2 brachydactyly;Acromesomelic dysplasia 3 Likely benign (Jul 12, 2022)1629430
4-95104460-C-T Brachydactyly Uncertain significance (Jan 12, 2018)906583
4-95104462-C-T Inborn genetic diseases Uncertain significance (Dec 21, 2022)2338263

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BMPR1Bprotein_codingprotein_codingENST00000440890 11400481
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9990.00137125726071257330.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2702782910.9550.00001483490
Missense in Polyphen115141.810.810961653
Synonymous-0.67910899.41.090.00000486999
Loss of Function4.55228.00.07140.00000145337

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00009050.0000905
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00009430.0000924
European (Non-Finnish)0.000008840.00000879
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0001640.000163

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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