SPRED1
Chr 15ADsprouty related EVH1 domain containing 1
Also known as: LGSS, NFLS, PPP1R147, hSpred1, spred-1
The SPRED1 protein regulates activation of the MAP kinase cascade by forming homodimers or heterodimers with SPRED2, and is phosphorylated by tyrosine kinases in response to growth factors. Loss-of-function mutations cause Legius syndrome (also known as neurofibromatosis type 1-like syndrome), which follows autosomal dominant inheritance. The pathogenic mechanism involves loss of normal MAP kinase regulation due to reduced SPRED1 function.
Definitive — sufficient evidence for diagnostic panels
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).
Literature Evidence
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
SPRED1 · 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