BMPR1B

Chr 4ARAD

bone morphogenetic protein receptor type 1B

Also known as: ALK-6, ALK6, AMD3, AMDD, BDA1D, BDA2, CDw293

This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

Primary Disease Associations & Inheritance

Acromesomelic dysplasia 3MIM #609441
AR
Brachydactyly, type A1, DMIM #616849
AD
Brachydactyly, type A2MIM #112600
AD
UniProtBrachydactyly A2
UniProtBrachydactyly A1, D
0
Active trials
38
Pubs (1 yr)
46
P/LP submissions
25%
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryBMPR1B
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Gene-Disease Validity (ClinGen)
pulmonary arterial hypertension · UDDisputed

Disputed — evidence questions this relationship

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 220 VUS of 476 total submissions
📖
GeneReview available — BMPR1B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.999
Z-score 4.55
OE 0.07 (0.030.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.27Z-score
OE missense 0.96 (0.861.05)
278 obs / 291.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.23)
00.351.4
Missense OE0.96 (0.861.05)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 2 / 28.0Missense obs/exp: 278 / 291.0Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBMPR1B-related brachydactylyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4785th %ile
GOF
0.5465th %ile
LOF
0.62top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNOverexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis.PMID:32714600

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

476 submitted variants in ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic12
VUS220
Likely Benign112
Benign69
Conflicting17
28
Pathogenic
12
Likely Pathogenic
220
VUS
112
Likely Benign
69
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
5
19
0
28
Likely Pathogenic
1
5
6
0
12
VUS
1
150
67
2
220
Likely Benign
1
19
43
49
112
Benign
0
6
59
4
69
Conflicting
17
Total718519455458

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BMPR1B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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