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 subunits of a disulfide-linked homodimer,... See more...

Aliases for BMP15 Gene

Aliases for BMP15 Gene

  • Bone Morphogenetic Protein 15 2 3 4 5
  • GDF9B 2 3 4
  • Growth/Differentiation Factor 9B 3 4
  • BMP-15 4
  • GDF-9B 4
  • BMP15 5
  • ODG2 3
  • POF4 3

External Ids for BMP15 Gene

Previous GeneCards Identifiers for BMP15 Gene

  • GC0XP049198
  • GC0XP048656
  • GC0XP049338
  • GC0XP049570
  • GC0XP050486
  • GC0XP050670
  • GC0XP048097

Summaries for BMP15 Gene

Entrez Gene Summary for BMP15 Gene

  • 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 subunits of a disulfide-linked homodimer, or alternatively, a heterodimer, with the related protein, growth differentiation factor 9 (GDF9). This protein plays a role in oocyte maturation and follicular development, through activation of granulosa cells. Defects in this gene are the cause of ovarian dysgenesis and are associated with premature ovarian failure. [provided by RefSeq, Aug 2016]

GeneCards Summary for BMP15 Gene

BMP15 (Bone Morphogenetic Protein 15) is a Protein Coding gene. Diseases associated with BMP15 include Ovarian Dysgenesis 2 and 46,Xx Sex Reversal 1. Among its related pathways are PEDF Induced Signaling and Akt Signaling. Gene Ontology (GO) annotations related to this gene include cytokine activity and transforming growth factor beta receptor binding. An important paralog of this gene is GDF9.

UniProtKB/Swiss-Prot Summary for BMP15 Gene

  • May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth.

Gene Wiki entry for BMP15 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for BMP15 Gene

Genomics for BMP15 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for BMP15 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ050707 Enhancer 0.7 Ensembl CraniofacialAtlas 12.5 -202.3 -202334 2 ZIC2 FEZF1 ZNF341 PRDM6 HNF4A PKNOX1 ZNF660 POLR2A ARNT SCRT2 BMP15 lnc-DGKK-4 piR-32325-209 SHROOM4 DGKK
GH0XJ050798 Enhancer 0.5 ENCODE 11.2 -111.1 -111095 1.8 ATF2 ZNF644 HLF TCF7 ZNF7 SCRT2 BMP15 SHROOM4 FJ601684-485 DGKK
GH0XJ050945 Enhancer 0.2 Ensembl 12.1 +34.4 34366 0.2 BMP15 RF00994-1176 piR-59907-036 MG828814 NUDT10
GH0XJ050689 Enhancer 0.2 Ensembl 12.1 -221.4 -221434 0.2 BMP15 lnc-DGKK-4 piR-32470-076 SHROOM4 DGKK
GH0XJ050913 Enhancer 0.2 Ensembl 0.7 +3.2 3166 0.2 BMP15 HSALNG0137902 NUDT10
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around BMP15 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for BMP15

Top Transcription factor binding sites by QIAGEN in the BMP15 gene promoter:
  • AML1a
  • Chx10
  • MIF-1
  • NF-E2
  • NF-E2 p45
  • Nkx2-5
  • POU2F1
  • POU2F1a
  • RP58
  • STAT5A

Genomic Locations for BMP15 Gene

Latest Assembly
chrX:50,910,735-50,916,641
(GRCh38/hg38)
Size:
5,907 bases
Orientation:
Plus strand

Previous Assembly
chrX:50,653,735-50,659,641
(GRCh37/hg19 by Entrez Gene)
Size:
5,907 bases
Orientation:
Plus strand

chrX:50,653,784-50,659,607
(GRCh37/hg19 by Ensembl)
Size:
5,824 bases
Orientation:
Plus strand

Genomic View for BMP15 Gene

Genes around BMP15 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BMP15 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BMP15 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for BMP15 Gene

Proteins for BMP15 Gene

  • Protein details for BMP15 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95972-BMP15_HUMAN
    Recommended name:
    Bone morphogenetic protein 15
    Protein Accession:
    O95972
    Secondary Accessions:
    • Q17RM6
    • Q5JST1
    • Q9UMS1

    Protein attributes for BMP15 Gene

    Size:
    392 amino acids
    Molecular mass:
    45055 Da
    Quaternary structure:
    • Homodimer. But, in contrast to other members of this family, cannot be disulfide-linked.
    Miscellaneous:
    • The mature protein migrates in two distinct mature proteins, P16 (16KDa) and P17 (17KDa).
    • Ovarian physiology and fertility are controlled by endocrine and paracrine signals. These act in a species-dependent manner and determine the ovulation quota in different mammalian species. While humans, and mammals such as the cow or red deer, normally ovulate only one egg per cycle, other mammals such as mouse and pig can ovulate in excess of ten per cycle. The mechanisms that regulate the species-specific differences in the number of follicles that go onto ovulate during each reproductive cycle are poorly understood. According to PubMed:21970812, mRNA expression levels of GDF9 and BMP15 are tightly coregulated within each species and influence species-specific ovulation-rates.

neXtProt entry for BMP15 Gene

Post-translational modifications for BMP15 Gene

  • Glycosylation at Asn87, Asn147, Asn237, Thr277, and Asn373
  • Modification sites at PhosphoSitePlus

Other Protein References for BMP15 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for BMP15 Gene

Domains & Families for BMP15 Gene

Gene Families for BMP15 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for BMP15 Gene

InterPro:
Blocks:
  • Transforming growth factor beta (TGFb)
  • Inhibin alpha chain signature

Suggested Antigen Peptide Sequences for BMP15 Gene

GenScript: Design optimal peptide antigens:
  • Growth/differentiation factor 9B (BMP15_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95972

UniProtKB/Swiss-Prot:

BMP15_HUMAN :
  • Belongs to the TGF-beta family.
Family:
  • Belongs to the TGF-beta family.
genes like me logo Genes that share domains with BMP15: view

Function for BMP15 Gene

Molecular function for BMP15 Gene

UniProtKB/Swiss-Prot Function:
May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth.
GENATLAS Biochemistry:
bone morphogenetic protein 15,expressed in oocytes,co-localized with GDF9,and likely involved in follicular development

Gene Ontology (GO) - Molecular Function for BMP15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IBA 21873635
GO:0008083 growth factor activity IEA --
GO:0070698 type I activin receptor binding IBA 21873635
genes like me logo Genes that share ontologies with BMP15: view
genes like me logo Genes that share phenotypes with BMP15: view

Human Phenotype Ontology for BMP15 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for BMP15 Gene

MGI Knock Outs for BMP15:

miRNA for BMP15 Gene

miRTarBase miRNAs that target BMP15

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BMP15

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for BMP15 Gene

Localization for BMP15 Gene

Subcellular locations from UniProtKB/Swiss-Prot for BMP15 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for BMP15 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 4
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
peroxisome 1
cytosol 1
golgi apparatus 1
lysosome 0

Gene Ontology (GO) - Cellular Components for BMP15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA 21873635
GO:0005737 cytoplasm IEA --
GO:0005788 endoplasmic reticulum lumen TAS --
genes like me logo Genes that share ontologies with BMP15: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for BMP15 Gene

Pathways & Interactions for BMP15 Gene

PathCards logo

SuperPathways for BMP15 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.57
.51
.47
.46
.43
2 TGF-Beta Pathway
.60
.60
.57
.51
.43
.40
3 Akt Signaling
.60
.60
.55
4 ERK Signaling
.61
.61
.51
5 PAK Pathway
.56
.56
genes like me logo Genes that share pathways with BMP15: view

Pathways by source for BMP15 Gene

27 Qiagen pathways for BMP15 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Endothelin-1 Signaling Pathway
  • ERK Signaling

SIGNOR curated interactions for BMP15 Gene

Activates:

Gene Ontology (GO) - Biological Process for BMP15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001541 ovarian follicle development IEA --
GO:0007292 female gamete generation TAS 9849956
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation IBA 21873635
GO:0030509 BMP signaling pathway IBA 21873635
GO:0043687 post-translational protein modification TAS --
genes like me logo Genes that share ontologies with BMP15: view

Drugs & Compounds for BMP15 Gene

(1) Drugs for BMP15 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with BMP15: view

Transcripts for BMP15 Gene

mRNA/cDNA for BMP15 Gene

1 REFSEQ mRNAs :
3 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BMP15

Alternative Splicing Database (ASD) splice patterns (SP) for BMP15 Gene

No ASD Table

Relevant External Links for BMP15 Gene

GeneLoc Exon Structure for
BMP15

Expression for BMP15 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for BMP15 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for BMP15 Gene

This gene is overexpressed in Testis (x35.6), Ovary (x8.8), Cervix - Endocervix (x4.4), and Lung (x4.1).

Protein differential expression in normal tissues from HIPED for BMP15 Gene

This gene is overexpressed in Monocytes (64.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for BMP15 Gene



Protein tissue co-expression partners for BMP15 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for BMP15

SOURCE GeneReport for Unigene cluster for BMP15 Gene:

Hs.532692

Phenotype-based relationships between genes and organs from Gene ORGANizer for BMP15 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • skeleton
Regions:
Head and neck:
  • brain
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • pituitary gland
  • skull
Thorax:
  • breast
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Pelvis:
  • ovary
  • pelvis
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vulva
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • hair
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with BMP15: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Evidence on tissue expression from TISSUES for BMP15 Gene

Orthologs for BMP15 Gene

This gene was present in the common ancestor of chordates.

Orthologs for BMP15 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia BMP15 29 30
  • 99.23 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia BMP15 29 30
  • 83.46 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia BMP15 29 30
  • 82.32 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Bmp15 29 16 30
  • 75.95 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Bmp15 29
  • 75.62 (n)
Oppossum
(Monodelphis domestica)
Mammalia BMP15 30
  • 52 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia BMP15 30
  • 43 (a)
OneToOne
Chicken
(Gallus gallus)
Aves BMP15 29 30
  • 54.26 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia BMP15 30
  • 38 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100485893 29
  • 53.53 (n)
Str.19786 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.18594 29
Zebrafish
(Danio rerio)
Actinopterygii bmp15 29 30
  • 46.92 (n)
OneToOne
wufi35a05 29
Species where no ortholog for BMP15 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for BMP15 Gene

ENSEMBL:
Gene Tree for BMP15 (if available)
TreeFam:
Gene Tree for BMP15 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for BMP15: view image
Alliance of Genome Resources:
Additional Orthologs for BMP15

Paralogs for BMP15 Gene

genes like me logo Genes that share paralogs with BMP15: view

Variants for BMP15 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for BMP15 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
1034178 Pathogenic: Ovarian dysgenesis 2 50,915,771(+) C/T
NM_005448.2(BMP15):c.343C>T (p.Gln115Ter)
NONSENSE
1034179 Pathogenic: Ovarian dysgenesis 2 50,916,343(+) G/A
NM_005448.2(BMP15):c.915G>A (p.Trp305Ter)
NONSENSE
913022 Uncertain Significance: Ovarian dysgenesis 2 50,916,239(+) G/T
NM_005448.2(BMP15):c.811G>T (p.Gly271Cys)
MISSENSE
913023 Uncertain Significance: Ovarian dysgenesis 2 50,916,348(+) A/G
NM_005448.2(BMP15):c.920A>G (p.His307Arg)
MISSENSE
914978 Benign: Ovarian dysgenesis 2 50,910,945(+) C/T
NM_005448.2(BMP15):c.162C>T (p.Gly54=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for BMP15 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for BMP15 Gene

Variant ID Type Subtype PubMed ID
dgv2293e212 CNV loss 25503493

Variation tolerance for BMP15 Gene

Residual Variation Intolerance Score: 85.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.30; 81.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for BMP15 Gene

Human Gene Mutation Database (HGMD)
BMP15
SNPedia medical, phenotypic, and genealogical associations of SNPs for
BMP15
Leiden Open Variation Database (LOVD)
BMP15

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for BMP15 Gene

Disorders for BMP15 Gene

MalaCards: The human disease database

(16) MalaCards diseases for BMP15 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search BMP15 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

BMP15_HUMAN
  • Ovarian dysgenesis 2 (ODG2) [MIM:300510]: A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. {ECO:0000269 PubMed:15136966}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Premature ovarian failure 4 (POF4) [MIM:300510]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269 PubMed:16464940, ECO:0000269 PubMed:16508750, ECO:0000269 PubMed:16645022, ECO:0000269 PubMed:19263482, ECO:0000269 PubMed:19438907}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for BMP15

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with BMP15: view

No data available for Genatlas for BMP15 Gene

Publications for BMP15 Gene

  1. Missense mutations in the BMP15 gene are associated with ovarian failure. (PMID: 16508750) Dixit H … Singh L (Human genetics 2006) 3 4 22 40 72
  2. BMP15 mutations associated with primary ovarian insufficiency cause a defective production of bioactive protein. (PMID: 19263482) Rossetti R … Persani L (Human mutation 2009) 3 4 22 40
  3. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. (PMID: 16645022) Laissue P … Veitia RA (European journal of endocrinology 2006) 3 4 22 40
  4. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. (PMID: 15136966) Di Pasquale E … Persani L (American journal of human genetics 2004) 3 4 22 72
  5. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. (PMID: 9849956) Dube JL … Matzuk MM (Molecular endocrinology (Baltimore, Md.) 1998) 2 3 4 22

Products for BMP15 Gene

Sources for BMP15 Gene