BMPR1A

Chr 10AD

bone morphogenetic protein receptor type 1A

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

BMPR1A encodes a transmembrane serine/threonine kinase receptor that binds bone morphogenetic proteins and activates SMAD transcriptional regulators to control chondrocyte differentiation and adipogenesis. Mutations cause autosomal dominant juvenile polyposis syndrome and hereditary mixed polyposis syndrome, which present with intestinal polyps and increased colorectal cancer risk. The gene is highly constrained against loss-of-function variants (pLI 0.90, LOEUF 0.36), indicating that such mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.352 OMIM phenotypes
Clinical SummaryBMPR1A
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Gene-Disease Validity (ClinGen)
juvenile polyposis syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.903
Z-score 4.19
OE 0.17 (0.090.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.92Z-score
OE missense 0.69 (0.610.77)
206 obs / 299.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.090.35)
00.351.4
Missense OE0.69 (0.610.77)
00.61.4
Synonymous OE0.97
01.21.6
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
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

Literature Evidence

LOFGermline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposisPMID:11381269

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

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗