BMPER

Chr 7AR

BMP binding endothelial regulator

Also known as: CRIM3, CV-2, CV2

NCBI Gene: 168667 ENSG00000164619 UniProt: Q8N8U9 OMIM: 608699

The protein is a secreted inhibitor of bone morphogenetic protein (BMP) function that regulates BMP responsiveness in osteoblasts and chondrocytes. Mutations cause diaphanospondylodysostosis, a lethal skeletal disorder with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation (LOEUF 0.663), consistent with recessive disease requiring biallelic mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.661 OMIM phenotype

Clinical Summary— BMPER

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

22 unique Pathogenic / Likely Pathogenic· 208 VUS of 441 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.000

Z-score 3.21

OE 0.44 (0.30–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.92–1.09)

380 obs / 380.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.30–0.66)

0≤0.351.4

Missense OE?1.00 (0.92–1.09)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 17 / 38.5Missense obs/exp: 380 / 380.6Syn Z: 0.28

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveBMPER-related diaphanospondylodysostosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7133th %ile

GOF

0.6736th %ile

LOF

0.2774th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

441 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic8

VUS208

Likely Benign130

Benign57

Conflicting17

Pathogenic

Likely Pathogenic

208

VUS

130

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	1	2	0	14
Likely Pathogenic	5	2	1	0	8
VUS	0	157	51	0	208
Likely Benign	0	4	59	67	130
Benign	0	2	45	10	57
Conflicting	—				17
Total	16	166	158	77	434

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap BMPER — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →