BMP8A

Chr 1

bone morphogenetic protein 8a

Also known as: OP-2, Op2

The protein is a secreted signaling molecule that induces cartilage and bone formation and regulates thermogenesis and energy balance through brown adipose tissue and hypothalamic pathways. Mutations cause autosomal recessive hypogonadotropic hypogonadism with failure to undergo puberty. The gene is highly constrained against loss-of-function variants, suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.35
Clinical SummaryBMP8A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.000
Z-score 0.67
OE 0.80 (0.491.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.27Z-score
OE missense 0.73 (0.630.85)
128 obs / 175.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.491.35)
00.351.4
Missense OE0.73 (0.630.85)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 10 / 12.6Missense obs/exp: 128 / 175.3Syn Z: 0.14
DN
0.6551th %ile
GOF
0.4382th %ile
LOF
0.3744th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BMP8A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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