BMPER

protein-coding

BMP binding endothelial regulator, the group of Cysteine rich transmembrane BMP regulators

Gene summary

This gene encodes a secreted protein that interacts with, and inhibits bone morphogenetic protein (BMP) function. It has been shown to inhibit BMP2- and BMP4-dependent osteoblast differentiation and BMP-dependent differentiation of the chondrogenic cells. Mutations in this gene are associated with a lethal skeletal disorder, diaphanospondylodysostosis. [provided by RefSeq, Dec 2011]

MANE transcript

NM_001365308.1

Inheritance

ClinVar variants

P:20U:160B:97

Top phenotype

Diaphanospondylodysostosis

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr7:33,904,308-34,156,427

External References & Databases

Ensembl (ENSG00000164619)

Transcript & Mutation Effects

hg38 • Region Span ~252.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

diaphanospondylodysostosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011946

Submitter: Orphanet

diaphanospondylodysostosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011946

Submitter: PanelApp Australia

diaphanospondylodysostosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011946

Submitter: Labcorp Genetics (formerly Invitae)

diaphanospondylodysostosisDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011946

Submitter: G2P

Clinical Genomic Database (CGD)

DiaphanospondylodysostosisAR

Manifestation: Craniofacial; Musculoskeletal; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 20869035; 30006055

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BMPER variants in ClinVar

6 Conditions Cataloged

not providedTotal: 244

Inborn genetic diseasesTotal: 102

DiaphanospondylodysostosisTotal: 65

not specifiedTotal: 19

BMPER-related disorderTotal: 8

HP:0003549Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365308.1. 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				79 clinvar	5 clinvar	84
missense	1 clinvar	2 clinvar	160 clinvar	11 clinvar	2 clinvar	176
nonsense	8 clinvar	3 clinvar				11
start loss						0
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	12	8	160	90	7	277

Highest pathogenic variant AF is 0.000015489333

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365308.1	RefSeq	NP_001352237.1	15	MANE Select
ENST00000649409.2	Ensembl	ENSP00000497748.1	15	MANE Select
NM_001410872.1	RefSeq	NP_001397801.1	14	Standard
NM_133468.5	RefSeq	NP_597725.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bmper	Danio rerio	Structure: blood cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

bmper

Danio rerio

Structure: blood cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ureteric bud development
blood vessel endothelial cell proliferation involved in sprouting angiogenesis
regulation of endothelial cell migration
negative regulation of BMP signaling pathway
endothelial cell activation

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297161
Coding exons: 15
Length: 250962
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0102	380	381	0.999	0.0000228	4492
Missense (PolyPhen)		94	118.75	0.79156		1415
Synonymous	0.284	141	145	0.970	0.00000919	1256
Loss of Function	3.21	17	38.5	0.442	0.00000201	455

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.0021	0.0021	notable
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibitor of bone morphogenetic protein (BMP) function, it may regulate BMP responsiveness of osteoblasts and chondrocytes. {ECO:0000269|PubMed:14766204}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.616
RVIS EVS: 0.07
RVIS percentile EVS: 59.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.261

Gene Damage Prediction

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