MAP3K7
Chr 6ADmitogen-activated protein kinase kinase kinase 7
Also known as: CSCF, FMD2, MEKK7, TAK1, TGF1a
MAP3K7 encodes a serine/threonine kinase that mediates signal transduction for multiple pathways including TGF-beta, BMP, and cytokine signaling, and serves as a key activator of NF-kappa-B and MAPK pathways in response to environmental stresses. Mutations cause autosomal dominant developmental delay, intellectual disability, and multiple congenital anomalies, often with cardiac defects and distinctive facial features. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.21), reflecting its essential role in cellular signaling pathways.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
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
234 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 | 9 | 11 | 0 | 20 |
Likely Pathogenic | 0 | 8 | 0 | 0 | 8 |
VUS | 8 | 86 | 22 | 4 | 120 |
Likely Benign | 0 | 5 | 41 | 24 | 70 |
Benign | 0 | 1 | 5 | 1 | 7 |
Conflicting | — | 9 | |||
| Total | 8 | 109 | 79 | 29 | 234 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MAP3K7 · 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