DCTN5
Chr 16dynactin subunit 5
This gene encodes a subunit of the dynactin complex that activates dynein for transport along microtubules, with the protein serving as a component of the pointed-end subcomplex that binds membranous cargo. Mutations cause autosomal recessive spastic paraplegia-78, a neurological disorder affecting motor function. The gene shows tolerance to loss-of-function variation (low pLI score), consistent with the recessive inheritance pattern observed in affected individuals.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
67 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 | 27 | 0 | 27 |
Likely Pathogenic | 1 | 0 | 3 | 0 | 4 |
VUS | 0 | 20 | 5 | 0 | 25 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 1 | 20 | 37 | 0 | 58 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DCTN5 · 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