GPM6A
Chr 4glycoprotein M6A
Also known as: GPM6, M6A
The protein functions in neuronal differentiation and migration, neurite outgrowth, and synaptic plasticity through calcium channel activity and MAPK signaling pathways. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delays, typically with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.22), indicating intolerance to protein-truncating mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
105 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 74 |
Likely Pathogenic | — | — | — | — | 2 |
VUS | — | — | — | — | 16 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 0 |
| Total | — | 93 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GPM6A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools