BMP15

bone morphogenetic protein 15, the group of Bone morphogenetic proteins

Basic information

Region (hg38): X:50910735-50916641

Links

ENSG00000130385 ∙ NCBI:9210 ∙ OMIM:300247 ∙ HGNC:1068 ∙ Uniprot:O95972 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ovarian dysgenesis 2 (Moderate), mode of inheritance: AD
• 46 XX gonadal dysgenesis (Supportive), mode of inheritance: AD
• ovarian dysgenesis 2 (Strong), mode of inheritance: XL
• ovarian dysgenesis 2 (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian dysgenesis 2	XL	Obstetric	Genetic knowledge may allow reproductive capabilities such as via egg preservation	Endocrine; Genitourinary; Obstetric	15136966; 16508750; 19263482

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BMP15 gene.

• Inborn_genetic_diseases (37 variants)
• Ovarian_dysgenesis_2 (24 variants)
• not_provided (12 variants)
• BMP15-related_disorder (5 variants)
• Premature_ovarian_failure_4 (4 variants)
• not_specified (2 variants)
• Genetic_non-acquired_premature_ovarian_failure (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMP15 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005448.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense	5	3	39	11	1	59
nonsense	2					2
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)						0
Total	7	4	39	13	3

Highest pathogenic variant AF is 0.00019167423

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BMP15	protein_coding	protein_coding	ENST00000252677	2	5824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000183	0.722	125707	4	11	125722	0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0699	157	159	0.984	0.0000127	2547
Missense in Polyphen		34	36.963	0.91984		606
Synonymous	0.0609	56	56.6	0.990	0.00000405	794
Loss of Function	0.948	7	10.3	0.681	8.83e-7	143

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000188	0.000160
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000137	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000524	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in follicular development. Oocyte- specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth. {ECO:0000269|PubMed:18227435}.
• Disease: DISEASE: 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 mutations affecting the gene represented in this entry.; DISEASE: 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 mutations affecting the gene represented in this entry.
• Pathway: Ovarian steroidogenesis - Homo sapiens (human);TGF-Core;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;TGF-beta super family signaling pathway canonical;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;BMP signaling Dro (Consensus)

Recessive Scores

• pRec: 0.191

Intolerance Scores

• loftool: 0.215
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.66

Haploinsufficiency Scores

• pHI: 0.413
• hipred: N
• hipred_score: 0.229

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.223

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bmp15
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: bmp15
• Affected structure: ovarian follicle
• Phenotype tag: abnormal
• Phenotype quality: maturity

Gene ontology

• Biological process: ovarian follicle development;female gamete generation;regulation of signaling receptor activity;positive regulation of pathway-restricted SMAD protein phosphorylation;BMP signaling pathway;regulation of apoptotic process;regulation of MAPK cascade;post-translational protein modification;cellular protein metabolic process;positive regulation of transcription, DNA-templated;cell development;granulosa cell development;SMAD protein signal transduction
• Cellular component: extracellular space;endoplasmic reticulum lumen
• Molecular function: cytokine activity;transforming growth factor beta receptor binding;growth factor activity