BMP4

Chr 14AD

bone morphogenetic protein 4

Also known as: BMP2B, BMP2B1, MCOPS6, OFC11, ZYME

NCBI Gene: 652 ENSG00000125378 UniProt: P12644 OMIM: 112262

This protein is a secreted growth factor of the TGF-beta superfamily that regulates essential developmental processes including neurogenesis, vascular development, and tooth formation by binding to BMP receptors and activating SMAD transcription factors. Mutations cause autosomal dominant microphthalmia and orofacial clefts, affecting craniofacial and ocular development. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.33), indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microphthalmia, syndromic 6MIM #607932

Orofacial cleft 11MIM #600625

UniProtNon-syndromic orofacial cleft 11

Clinical highlights

Gene-disease validity (ClinGen)

BMP4-related ocular growth disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

332

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· G2P