SIPA1L2
Chr 1signal induced proliferation associated 1 like 2
Also known as: SPAL2, SPAR2
This gene encodes a GTPase-activating protein that regulates the small GTPase Rap through its GTPase activating domain, PDZ domain, and C-terminal coiled-coil domain with leucine zipper. Mutations cause neurodevelopmental disorders with intellectual disability and autism spectrum features, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29), indicating intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SIPA1L2 · 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