MAP3K15
Chr Xmitogen-activated protein kinase kinase kinase 15
Also known as: ASK3, bA723P2.3
The MAP3K15 protein is a serine/threonine kinase that functions as an upstream activator in the p38 MAPK signaling cascade, phosphorylating and activating MAP kinase kinases in response to cellular stress and osmotic changes. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene shows tolerance to loss-of-function variants (low constraint), consistent with the recessive inheritance pattern observed in affected patients.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is gain-of-function.
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
500 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 | 82 | 0 | 82 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 4 | 206 | 23 | 0 | 233 |
Likely Benign | 2 | 10 | 5 | 17 | 34 |
Benign | 0 | 9 | 19 | 4 | 32 |
Conflicting | — | 6 | |||
| Total | 6 | 225 | 132 | 21 | 390 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MAP3K15 · 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