MAPK8IP3
Chr 16ADmitogen-activated protein kinase 8 interacting protein 3
Also known as: JIP-3, JIP3, JSAP1, NEDBA, SYD2, syd
The protein functions as a scaffold protein that mediates JNK signaling and regulates axonal transport by bridging interactions between motor proteins like kinesin-1 and neuronal cargo, promoting axon elongation and cortical neuronal migration during brain development. Mutations cause neurodevelopmental disorder with or without variable brain abnormalities with autosomal dominant inheritance. This gene is highly constrained against loss-of-function mutations (pLI ~1.0, LOEUF 0.15), indicating that even single functional copies are critical for normal neurodevelopment.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MAPK8IP3 · 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
External Resources
Links to major genomics databases and tools