APLP2
Chr 11amyloid beta precursor like protein 2
Also known as: APLP-2, APPH, APPL2, CDEBP
APLP2 encodes amyloid precursor-like protein 2, which inhibits multiple coagulation factors and proteases including trypsin, chymotrypsin, and factor XIA, and works synergistically with amyloid precursor protein to mediate neuromuscular transmission and synaptic plasticity. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and neuromotor dysfunction. The gene shows significant constraint against loss-of-function variation (LOEUF 0.393), indicating intolerance to protein-truncating mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
APLP2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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