DCTN3

Chr 9

dynactin 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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.54
Clinical SummaryDCTN3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.54LOEUF
pLI 0.000
Z-score 0.21
OE 0.94 (0.591.54)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.90 (0.771.07)
96 obs / 106.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.591.54)
00.351.4
Missense OE0.90 (0.771.07)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 11 / 11.8Missense obs/exp: 96 / 106.1Syn Z: -0.30
DN
0.7229th %ile
GOF
0.6442th %ile
LOF
0.3356th %ile

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.

DNprediction above median
GOFprediction above median

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

0 submitted variants 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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC