BMP7

protein-coding

bone morphogenetic protein 7, the group of Bone morphogenetic proteins

Gene summary

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, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001719.3

Inheritance

ClinVar variants

P:2U:74B:24

Top phenotype

BMP7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr20:57,168,753-57,266,641

External References & Databases

Ensembl (ENSG00000101144)

Transcript & Mutation Effects

hg38 • Region Span ~97.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated craniosynostosisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015337

Submitter: PanelApp Australia

congenital anomaly of kidney and urinary tractLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019719

Submitter: PanelApp Australia

Mayer-Rokitansky-Kuster-Hauser syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0017771

Submitter: PanelApp Australia

multiple congenital anomalies/dysmorphic syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

hypospadiasLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005345

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BMP7 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 54

not specifiedTotal: 50

BMP7-related disorderTotal: 12

Congenital anomaly of kidney and urinary tractTotal: 3

Congenital heart defects, multiple types, 4Total: 1

Atrial septal defect 8Total: 1

Congenital total pulmonary venous return anomalyTotal: 1

Tetralogy of FallotTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001719.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	15 clinvar	6 clinvar	22
missense	2 clinvar		69 clinvar		3 clinvar	74
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	2	0	74	15	9	100

Highest pathogenic variant AF is 0.000008054962

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001719.3	RefSeq	NP_001710.1	7	MANE Select
ENST00000395863.8	Ensembl	ENSP00000379204.3	7	MANE Select
ENST00000395864.7	Ensembl	ENSP00000379205.3	6	Standard
ENST00000395864.8	Ensembl	ENSP00000379205.3	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bmp7a	Danio rerio	Structure: erythroid lineage cell Quality: absent abnormal

Gene / Model

Organism

Observed Phenotype

bmp7a

Danio rerio

Structure: erythroid lineage cell

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta signaling pathway - Homo sapiens (human)
Axon guidance - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
TGF-Core

Biological Process

skeletal system development
ossification
metanephros development
ureteric bud development
mesoderm formation

Molecular Function

cytokine activity
transforming growth factor beta receptor binding
protein binding
growth factor activity
heparin binding

Cellular Component

extracellular region
extracellular space
vesicle
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395863
Coding exons: 7
Length: 97882
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.78	190	273	0.696	0.0000182	2841
Missense (PolyPhen)		56	113.52	0.49333		1196
Synonymous	0.236	111	114	0.972	0.00000826	807
Loss of Function	2.90	5	18.5	0.271	9.60e-7	189

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis.;

Recessive Scores

pRec: 0.673

Intolerance Scores

LoFtool: 0.123
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.958

Gene Damage Prediction

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