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

ENSG00000138696 ∙ NCBI:658 ∙ OMIM:603248 ∙ HGNC:1077 ∙ Uniprot:O00238 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

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 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	29	3	33
missense	1	3	79	17	6	106
nonsense						0
start loss						0
frameshift						0
inframe indel		1				1
splice donor/acceptor (+/-2bp)				1		1
splice region			2	3	1	6
non coding			55	24	57	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)
4-94758053-G-C		Brachydactyly	Uncertain significance (Jan 13, 2018)
4-94875831-G-A		Brachydactyly	Uncertain significance (Jan 12, 2018)
4-94875846-A-G		Brachydactyly	Uncertain significance (Mar 02, 2018)
4-94875884-A-G		Brachydactyly	Benign (Jan 12, 2018)
4-94875896-T-C		BMPR1B-related disorder • Brachydactyly	Benign (Sep 16, 2019)
4-94996064-C-G		Brachydactyly	Uncertain significance (Feb 09, 2018)
4-94996135-G-T		Brachydactyly	Likely benign (Oct 02, 2017)
4-95051389-G-A			Likely benign (Feb 13, 2020)
4-95051585-C-T		Acromesomelic dysplasia 3	Uncertain significance (-)
4-95051729-G-A		BMPR1B-related disorder	Likely benign (Nov 25, 2019)
4-95051734-A-G		BMPR1B-related disorder	Benign (Jul 29, 2019)
4-95051768-A-G		BMPR1B-related disorder	Likely benign (Mar 16, 2019)
4-95051944-GCTTT-G			Benign (Jun 25, 2021)
4-95051945-C-T			Likely benign (Jul 18, 2020)
4-95052055-A-T			Benign (Nov 10, 2018)
4-95104151-T-G			Benign (Sep 04, 2018)
4-95104271-A-G			Likely benign (Mar 14, 2020)
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)
4-95104439-T-G		Type A2 brachydactyly;Acromesomelic dysplasia 3	Likely benign (Jul 12, 2022)
4-95104440-G-A		Acromesomelic dysplasia 3;Type A2 brachydactyly • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 15, 2023)
4-95104442-A-G		Type A2 brachydactyly;Acromesomelic dysplasia 3	Likely benign (Jan 02, 2024)
4-95104445-A-G		Type A2 brachydactyly;Acromesomelic dysplasia 3	Likely benign (Jul 12, 2022)
4-95104460-C-T		Brachydactyly	Uncertain significance (Jan 12, 2018)
4-95104462-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

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: 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

	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