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FLASH GENE
Symbol BMP15 contributors: mct/npt - updated : 02-04-2021
HGNC name bone morphogenetic protein 15
HGNC id 1068
Corresponding disease
ODG2 ovarian dysgenesis 2
Location Xp11.22      Physical location : 50.653.734 - 50.659.640
Synonym name
  • oocyte-derived growth factor
  • growth/differentiation factor 9B
  • Synonym symbol(s) GDF9B, POF4
    DNA
    TYPE functioning gene
    STRUCTURE 5.82 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - DMD DMD - [MAOA - TIMP1 ] - PHKA1 - XIST - PDHA1 - cen
    Authors Galloway (00)]
    Text [BMP15 ]
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1262 - 392 - Di Pasquale (2009)
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemovary    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegranulosa cell Homo sapiens
    Reproductiveoocyte Homo sapiens
    cell lineage oocytes of late primary follicles
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide of 17AA, five potential N-linked glycosylation sites
  • 244 AA proregion
  • a putative 125 AA C terminal mature peptide region
  • TGF-beta like domain
  • mono polymer homomer , heteromer , dimer
    isoforms Precursor cleaved by a consensus Arg-X-X-Arg to yield a C terminus mature domain
    HOMOLOGY
    interspecies ortholog to BMP15 sheep,mutated in infertile females FecX (Inverdale or Hanna)
    homolog to murine Bmp15
    homolog to C.elegans c52b9.1
    Homologene
    FAMILY
  • transforming growth factor beta superfamily
  • bone morphogenetic protein family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
    text secreted, colocalized with GDF9
    basic FUNCTION
  • likely involved in follicular development and oocyte maturation modulating selectively FSH function
  • could play a physiological role in the monotropic rise of FSH secretion by the pituitary during the estrous and menstrual cycle and in the negative regulation of FSH receptor in the ovary, plaiyng a major role in female fertility
  • oocyte-secreted factor critical for the regulation of ovarian physiology (Saito 2008)
  • ovarian follicle organizer whose adequate function is critical for female fertility (Rossetti 2009)
  • having a necessary and sufficient role for the specification of dorso-anterior structures (Di Pasquale 2009)
  • GDF9 and BMP15 are likely germ cell-specific factors in the testis, and GDF9 can modulate key Sertoli cell functions
  • play likely roles in corpus luteum activity
  • crucial role of GDF9 and BMP15 in female fertility
  • BMP15 and GDF9 promoted activation of human primordial follicles from girls/women in a dose-dependent manner, but GDF9 seems more beneficial
  • GDF9 and bone morphogenetic protein 15 (BMP15) are two proteins selectively expressed in the oocyte which are essential for normal fertility
  • GDF9 and bone morphogenetic protein 15 (BMP15) act synergistically to regulate granulosa cell proliferation and steroid production
  • GDF9 and BMP15 act synergistically to stimulate granulosa cell proliferation, a response that also involves species-specific non-SMAD signalling pathways
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS reproduction/sex
    text oogenesis
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • homodimer and heterodimer with GDF9
  • GDF9:BMP15 heterodimers are potent regulators of ovarian functions
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specifically interacts with BMP4 protein (blocks the epidermal-inducing activity of BMP4 protein) (Di Pasquale 2009)
  • GDF9/BMP15 synergistic interactions were specific such that neither factor could be replaced by an analogous TGFB superfamily member
  • oocyte-derived BMP15 decreases GJA1 activity between human granulosa cells by down-regulating Cx43 expression, most likely via a Smad-dependent signaling pathway
  • GDF9 and BMP15 and FSH Regulate AMH expression via modulation of H3K27AC in granulosa cells
  • interaction between Clock NR5A1/NR5A2 and BMP15 is likely to be involved in the fine-tuning of steroidogenesis by ovarian granulosa cells
  • cell & other
    REGULATION
    activated by cleaved by subtilisin-like convertases
    ASSOCIATED DISORDERS
    corresponding disease(s) ODG2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    associated with primary ovarian insufficiency cause a defective production of bioactive protein (Rossetti 2009)
    constitutional germinal mutation      
    in BMP15 associated with Primary Ovarian Insufficiencyreduce mature protein production, activity, or synergy with GDF9
    Susceptibility to premature ovarian failure (POF)
    Variant & Polymorphism other mutations minor cause of ovarian insufficiency and POF
    Candidate gene
    Marker
  • GDF9 and BMP15 mRNAs in cumulus granulosa cells may be considered as new molecular markers for predicting oocyte developmental potential
  • Therapy target
    ANIMAL & CELL MODELS