BMP5

protein-coding

bone morphogenetic protein 5, 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 and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]

MANE transcript

NM_021073.4

Inheritance

ClinVar variants

P:2U:69B:10

Top phenotype

BMP5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr6:55,753,653-55,875,590

External References & Databases

Ensembl (ENSG00000112175)

Transcript & Mutation Effects

hg38 • Region Span ~121.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

skeletal dysplasiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0018230

Submitter: PanelApp Australia

dysostosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0018234

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BMP5 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 68

BMP5-related disorderTotal: 12

not providedTotal: 4

Patellar aplasiaTotal: 2

Hypoplastic ischiopubic ramusTotal: 2

MicrotiaTotal: 2

Atrioventricular canal defectTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021073.4. 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				3 clinvar	2 clinvar	5
missense			68 clinvar	2 clinvar	3 clinvar	73
nonsense						0
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	0	2	69	5	5	81

Highest pathogenic variant AF is 0.000006581632

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_021073.4	RefSeq	NP_066551.1	7	MANE Select
ENST00000370830.4	Ensembl	ENSP00000359866.3	7	MANE Select
NM_001329754.2	RefSeq	NP_001316683.1	6	Standard
NM_001329756.2	RefSeq	NP_001316685.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bmp5	Danio rerio	Structure: perineuronal satellite cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

bmp5

Danio rerio

Structure: perineuronal satellite cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta signaling pathway - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
alk in cardiac myocytes
GPCR signaling-G alpha q
GPCR signaling-cholera toxin

Biological Process

skeletal system development
ossification
endocardial cushion formation
type B pancreatic cell development
pericardium morphogenesis

Molecular Function

cytokine activity
transforming growth factor beta receptor binding
growth factor activity
BMP receptor binding

Cellular Component

cellular_component
extracellular space
vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370830
Coding exons: 7
Length: 121920
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125745
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.625	228	256	0.890	0.0000144	2993
Missense (PolyPhen)		63	94.471	0.66687		1131
Synonymous	0.0172	87	87.2	0.998	0.00000468	863
Loss of Function	2.64	9	22.5	0.400	0.00000136	241

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces cartilage and bone formation.;

Recessive Scores

pRec: 0.260

Intolerance Scores

LoFtool: 0.465
RVIS EVS: 0.35
RVIS percentile EVS: 74.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.406

Gene Damage Prediction

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