DNM1
Chr 9ADARdynamin 1
Also known as: DEE31, DEE31A, DEE31B, DNM, EIEE31
The protein tubulates and severs membranes through its mechanochemical GTPase activity and is essential for clathrin-mediated endocytosis and vesicular trafficking processes. Mutations cause developmental and epileptic encephalopathy 31A (autosomal dominant) and 31B (autosomal recessive), with the gene being highly intolerant to loss-of-function variants. Disease can result from different mechanisms depending on the specific variant, with some mutations likely causing haploinsufficiency while others may act through dominant-negative or gain-of-function effects.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
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
400 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 | 5 | 7 | 6 | 0 | 18 |
Likely Pathogenic | 5 | 6 | 0 | 0 | 11 |
VUS | 8 | 168 | 27 | 8 | 211 |
Likely Benign | 0 | 1 | 64 | 73 | 138 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 6 | |||
| Total | 18 | 182 | 98 | 81 | 385 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DNM1 · 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
External Resources
Links to major genomics databases and tools