DCTN5

Chr 16

dynactin subunit 5

NCBI Gene: 84516 ENSG00000166847 UniProt: Q9BTE1 OMIM: 612962

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a component of the pointed-end subcomplex and is thought to bind membranous cargo. A pseudogene of this gene is located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.00

Clinical Summary— DCTN5

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.007

Z-score 1.58

OE 0.47 (0.25–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.69Z-score

OE missense 0.54 (0.43–0.67)

57 obs / 106.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.25–1.00)

0≤0.351.4

Missense OE?0.54 (0.43–0.67)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 5 / 10.6Missense obs/exp: 57 / 106.0Syn Z: 1.18

This gene — mechanism propensity

0.7132th %ile

GOF

0.6051th %ile

LOF

0.3552th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.