DCTN1
Chr 2ADARdynactin subunit 1
Also known as: DAP-150, DP-150, HMND14, P135
The encoded protein is the largest subunit of dynactin, which binds to microtubules and cytoplasmic dynein to facilitate intracellular transport including ER-to-Golgi transport, organelle movement, and axonogenesis. Mutations cause autosomal dominant distal hereditary motor neuronopathy type 14 and Perry syndrome, as well as autosomal recessive forms, through disruption of dynein-mediated axonal transport. The protein contains a conserved CAP-Gly domain that directly binds microtubules and interacts with dynein intermediate chains.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
600 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 | 1 | 0 | 4 | 0 | 5 |
Likely Pathogenic | 1 | 2 | 1 | 0 | 4 |
VUS | 15 | 246 | 27 | 5 | 293 |
Likely Benign | 0 | 8 | 147 | 101 | 256 |
Benign | 0 | 0 | 7 | 2 | 9 |
Conflicting | — | 3 | |||
| Total | 17 | 256 | 186 | 108 | 570 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DCTN1 · 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