DCTN3
Chr 9dynactin subunit 3
Also known as: DCTN-22, DCTN22
The protein is the smallest subunit of the dynactin complex, which activates the molecular motor dynein for transport along microtubules and is involved in diverse cellular functions including ER-to-Golgi transport, organelle movement, spindle formation, and axonogenesis. Mutations cause autosomal recessive spinal muscular atrophy with congenital bone fractures, a severe neuromuscular disorder affecting the spinal cord and skeletal system from birth. This gene shows extremely low constraint against loss-of-function variants (pLI near zero), indicating tolerance to such mutations in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-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.
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
120 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 | 63 | 0 | 63 |
Likely Pathogenic | 0 | 0 | 8 | 0 | 8 |
VUS | 0 | 26 | 10 | 0 | 36 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 26 | 81 | 0 | 107 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DCTN3 · 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