BMP8B

Chr 1

bone morphogenetic protein 8b

Also known as: BMP8, OP2

NCBI Gene: 656 ENSG00000116985 UniProt: P34820

This protein is a secreted signaling molecule of the TGF-beta superfamily that induces cartilage and bone formation and plays a role in calcium regulation and bone homeostasis. The gene is not highly constrained against loss-of-function variants (pLI 0.0002, LOEUF 1.27), and no definitive Mendelian disease associations have been established for this gene in the provided data.

ResearchSummary from RefSeq, UniProt

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. The encoded protein stimulates thermogenesis in brown adipose tissue. Expression of this gene may be downregulated in pancreatic cancer. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.27

Clinical Summary— BMP8B

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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

144 VUS of 165 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.96

OE 0.68 (0.38–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.86 (0.75–0.98)

146 obs / 170.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.38–1.27)

0≤0.351.4

Missense OE?0.86 (0.75–0.98)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 7 / 10.3Missense obs/exp: 146 / 170.5Syn Z: 0.85

This gene — mechanism propensity

0.6937th %ile

GOF

0.5071th %ile

LOF

0.3261th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

165 submitted variants in ClinVar

ClinVar

Classification Summary

VUS144

Likely Benign11

Benign2

Conflicting1

144

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	144	0	0	144
Likely Benign	0	6	1	4	11
Benign	0	1	1	0	2
Conflicting	—				1
Total	0	151	2	4	158

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap BMP8B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →