GPM6B

Chr X

glycoprotein M6B

Also known as: M6B

This gene encodes a membrane glycoprotein involved in neural development and regulation of osteoblast function and bone formation. Mutations cause autosomal recessive intellectual disability with seizures and behavioral abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), affecting both neurological and skeletal systems.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.59
Clinical SummaryGPM6B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.346
Z-score 2.58
OE 0.23 (0.100.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.99Z-score
OE missense 0.51 (0.420.63)
68 obs / 132.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.100.59)
00.351.4
Missense OE0.51 (0.420.63)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 3 / 13.1Missense obs/exp: 68 / 132.4Syn Z: -0.41
DN
0.5968th %ile
GOF
0.77top 25%
LOF
0.3647th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

GPM6B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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