BMPR1A

Chr 10AD

bone morphogenetic protein receptor type 1A

Also known as: 10q23del, ACVRLK3, ALK-3, ALK3, BMPR-1A, CD292, SKR5

NCBI Gene: 657ENSG00000107779UniProt: P36894OMIM: 601299

The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 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. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.352 OMIM phenotypes
Clinical Summary— BMPR1A
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Gene-Disease Validity (ClinGen)
juvenile polyposis syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — BMPR1A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.35LOEUF
pLI 0.903
Z-score 4.19
OE 0.17 (0.09–0.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.92Z-score
OE missense 0.69 (0.61–0.77)
206 obs / 299.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.17 (0.09–0.35)
0≤0.351.4
Missense OE?0.69 (0.61–0.77)
0≤0.61.4
Synonymous OE?0.97
0≤1.21.6
LoF obs/exp: 5 / 29.6Missense obs/exp: 206 / 299.4Syn Z: 0.27
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBMPR1A-related juvenile polypopsis syndrome, infantile formLOFAD

This gene — mechanism propensity

DN
0.4685th %ile
GOF
0.5562th %ile
LOF
0.61top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · LOEUF 0.35 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFGermline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis1

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

References

  1. 1.PMID 11381269 ↗

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

BMPR1A · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients