BMPR1A

Chr 10AD

bone morphogenetic protein receptor type 1A

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

NCBI Gene: 657ENSG00000107779UniProt: P36894

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]

Primary Disease Associations & Inheritance

Polyposis syndrome, hereditary mixed, 2MIM #610069
Polyposis, juvenile intestinalMIM #174900
AD
UniProtJuvenile polyposis syndrome
596
ClinVar variants
89
Pathogenic / LP
0.90
pLI score· haploinsufficient
3
Active trials
Clinical Summary— BMPR1A
🧬
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.
📋
ClinVar Variants
89 Pathogenic / Likely Pathogenic· 263 VUS of 596 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.92Z-score
OE missense 0.69 (0.61–0.77)
206 obs / 299.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.09–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.61–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 5 / 29.6Missense obs/exp: 206 / 299.4Syn Z: 0.27

ClinVar Variant Classifications

596 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic24
VUS263
Likely Benign189
Benign51
Conflicting4
65
Pathogenic
24
Likely Pathogenic
263
VUS
189
Likely Benign
51
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
36
0
29
0
65
Likely Pathogenic
16
3
5
0
24
VUS
7
231
25
0
263
Likely Benign
0
1
99
89
189
Benign
1
0
13
37
51
Conflicting
—4
Total60235171126596

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

View 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.

Gene2Phenotype Curations

BMPR1A-related juvenile polypopsis syndrome, infantile form

definitive
ADLoss Of FunctionAbsent Gene Product
Cancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Polyposis syndrome, hereditary mixed, 2

MIM #610069

Molecular basis of disorder known

Polyposis, juvenile intestinal

MIM #174900

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — BMPR1A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Predisposition to Colorectal Cancer: How Many and Which Genes to Test?
Rebuzzi F et al.·Int J Mol Sci
2023Review
Lethal variants in humans: lessons learned from a large molecular autopsy cohort.
Shamseldin HE et al.·Genome Med
2021Cohort
H3K27me3-modulated Hofbauer cell BMP2 signalling enhancement compensates for shallow trophoblast invasion in preeclampsia.
Deng J et al.·EBioMedicine
2023
Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.
Welch CL et al.·Genet Med
2023
Juvenile polyposis syndrome.
Brosens LA et al.·World J Gastroenterol
2011Review
Genetic landscape of a large cohort of Primary Ovarian Insufficiency: New genes and pathways and implications for personalized medicine.
Heddar A et al.·EBioMedicine
2022Cohort
Adenomatous Polyposis Phenotype in BMPR1A and SMAD4 Variant Carriers.
Rosner G et al.·Clin Transl Gastroenterol
2022
Juvenile polyposis syndrome: An overview.
Dal Buono A et al.·Best Pract Res Clin Gastroenterol
2022Review
A Novel Missense Variant of BMPR1A in Juvenile Polyposis Syndrome: Assessment of Structural and Functional Alternations.
Yang M et al.·Hum Mutat
2025Functional
Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer.
Boland CR et al.·Gastroenterology
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
BRCA1 MutationPOLD1 Gene MutationCDKN2A Mutation

An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results

RECRUITING
NCT05420064Phase NAMemorial Sloan Kettering Cancer CenterStarted 2022-12-01
Intervention Arm At-risk Relative/ARR ContactsMyGene PortalStandard of Care
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Lynch SyndromeLi Fraumeni SyndromePTEN Hamartoma Syndrome

Video Capsule Examination in Patients With Lynch Syndrome

RECRUITING
NCT06712095Phase NARoyal Marsden NHS Foundation TrustStarted 2024-03-04
Video capsule investigation

External Resources

Links to major genomics databases and tools