MXD4
Chr 4MAX dimerization protein 4
Also known as: MAD4, MST149, MSTP149, bHLHc12
The MXD4 protein is a transcriptional repressor that heterodimerizes with MAX protein to form DNA-binding complexes, antagonizing MYC transcriptional activity and suppressing cell transformation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene shows high constraint against loss-of-function variants, suggesting that even single functional copies may be insufficient for normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
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
187 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 | 128 | 0 | 128 |
Likely Pathogenic | 0 | 0 | 6 | 0 | 6 |
VUS | 0 | 28 | 13 | 0 | 41 |
Likely Benign | 0 | 0 | 0 | 1 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 28 | 147 | 1 | 176 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MXD4 · 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