BMPER

Chr 7AR

BMP binding endothelial regulator

Also known as: CRIM3, CV-2, CV2

NCBI Gene: 168667ENSG00000164619UniProt: Q8N8U9

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]

Primary Disease Associations & Inheritance

DiaphanospondylodysostosisMIM #608022
AR
462
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BMPER
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 214 VUS of 462 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.66LOEUF
pLI 0.000
Z-score 3.21
OE 0.44 (0.30–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.01Z-score
OE missense 1.00 (0.92–1.09)
380 obs / 380.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.30–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.92–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 17 / 38.5Missense obs/exp: 380 / 380.6Syn Z: 0.28

ClinVar Variant Classifications

462 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic11
VUS214
Likely Benign131
Benign57
Conflicting17
32
Pathogenic
11
Likely Pathogenic
214
VUS
131
Likely Benign
57
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
28
0
32
Likely Pathogenic
3
2
6
0
11
VUS
0
156
58
0
214
Likely Benign
0
4
60
67
131
Benign
0
2
45
10
57
Conflicting
—17
Total616519777462

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BMPER · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BMPER-related diaphanospondylodysostosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Diaphanospondylodysostosis

MIM #608022

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.
Wang G et al.·Adv Sci (Weinh)
2024Functional
SUGP2 p.(Arg639Gln) variant is involved in the pathogenesis of hemochromatosis via the CIRBP/BMPER signaling pathway.
Li Y et al.·Am J Hematol
2024
Further evidence for attenuated phenotype with variants in the BMPER gene causing DSD: Case report and literature review.
Batey N et al.·Eur J Med Genet
2022Review
FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome.
Wang SK et al.·Int Endod J
2023
Identification of conserved skeletal enhancers associated with craniosynostosis risk genes.
He 何璇 XA et al.·Hum Mol Genet
2024
Krüppel-like factor 15 regulates BMPER in endothelial cells.
Helbing T et al.·Cardiovasc Res
2010
BMPER is an endothelial cell regulator and controls bone morphogenetic protein-4-dependent angiogenesis.
Heinke J et al.·Circ Res
2008
Extending the phenotype of BMPER-related skeletal dysplasias to ischiospinal dysostosis.
Kuchinskaya E et al.·Orphanet J Rare Dis
2016
Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis.
Pi X et al.·Arterioscler Thromb Vasc Biol
2012
Expansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process.
Braun F et al.·Mol Genet Genomic Med
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools