SHISA6
Chr 17shisa family member 6
The protein regulates AMPA-type glutamate receptor function at synapses, maintaining high-frequency synaptic transmission by preventing receptor immobilization and synaptic depression. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, epilepsy, and progressive microcephaly. The gene is highly constrained against loss-of-function variants, reflecting its critical role in synaptic function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
128 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 11 | 0 | 11 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 110 | 4 | 0 | 114 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 110 | 15 | 0 | 125 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SHISA6 · 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