• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
BMPR1A (HGNC:1076) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
bone morphogenetic protein receptor type 1A
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
ACVRLK3
Alias symbols
ALK3, CD292
%HI
30.17(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.9(Read more about gnomAD pLI score)
LOEUF
0.36(Read more about gnomAD LOEUF score)
Cytoband
10q23.2
Genomic Coordinates
GRCh37/hg19: chr10:88516376-88687726 NCBI Ensembl UCSC
GRCh38/hg38: chr10:86755763-86932844 NCBI Ensembl UCSC
MANE Select Transcript
NM_004329.3 ENST00000372037.8 (Read more about MANE Select)
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 BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction. Mediates induction of adipogenesis by GDF6. May promote the expression of HAMP, potentially via its interaction with ... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-36549
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
06/24/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 11381269
    Howe et al. (2001) identified four BMPR1A germline truncation pathogenic variants in four juvenile polyposis kindreds. Genomic sequencing of BMPR1A in each of these juvenile polyposis kindreds disclosed these truncation pathogenic variants in all affected kindred members but not in normal individuals (figure 2). Individual Case Evidence: Segregation Among Similarly Affected Family Members • NM_004329.2(BMPR1A):c.44_47delTGTT (p.Leu15Serfs) • NM_004329.2(BMPR1A):c.715C>T (p.Gln239Ter) • NM_004329.2(BMPR1A):c.812G>A (p.Trp271Ter) • NM_004329.2(BMPR1A):c.961del (p.Phe320_Leu321insTer)
  • PUBMED: 15235019
    Howe et al (2004) performed a large cohort study including a total of 77 Juvenile polyposis (JP) cases. Germline BMPR1A gene pathogenic variants were identified in 16 cases (20.8%). These included ten truncation (including nonsense and deletion) variants and six missense mutations. Individual Case Evidence: Unknown Inheritance, total 10 cases
  • PUBMED: 23399955
    Ngeow et al (2013) performed a large prospective, referral-based study of 603 patients with moderate-load colorectal polyps. Twenty cases (3.3%) were identified carrying a BMPR1A pathogenic variants including twelve BMPR1A focal deletion and/or truncation variants and eight misssense variatns. All the BMPR1A pathogenic variants carriers were diagnosed with Juvenile polyposis and/or other types of cancers (supplementary table). Individual Case Evidence: Unknown Inheritance, total 12 cases
HI Evidence Comments:
BMPR1A is a type I receptor of the TGF-β superfamily, with a cysteine-rich extracellular region, an intracellular glycine–serinerich (GS) domain near the plasma membrane and an intracellular kinase domain. Loss of function pathogenic variants have been associated with Juvenile polyposis syndrome, an autosomal dominant condition that predisposes gene carriers to various types of tumors (see GeneReviews for additional information http://www.ncbi.nlm.nih.gov/books/NBK1469/) . As described above, Howe et al. (2001) first identified four BMPR1A germline truncation pathogenic variants in four juvenile polyposis kindreds. Further sequencing indicated the pathogenic variants were inherited and segregated with disease in these four families. Afterwards, many case reports and cohort studies further supported and provided additional evidence for the association between BMPR1A haploinsufficiency and Juvenile polyposis syndrome (PMID: 11381269, 15235019, 23399955). Other supporting evidence for BMPR1A haploinsufficiency includes but is not limited to: • Zhou et al. (2001) PubMed: 11536076 • Cao et al. (2006) PubMed: 16525031 • O'Riordan et al (2009) PMID: 19438883 • Gao et al. (2020) PMID: 32487124

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
There are currently no reports of focal duplications involving only BMPR1A, therefore the current triplosensitivity score is 0.

Genomic View

Select assembly: (NC_000010.10) (NC_000010.11)