DYNLRB2

Chr 16

dynein light chain roadblock-type 2

ENSG00000168589 UniProt: Q8TF09 OMIM: 607168

DYNLRB2 encodes a non-catalytic accessory component of the cytoplasmic dynein 1 complex that links dynein to cellular cargo and regulatory adapter proteins, facilitating retrograde transport of vesicles and organelles along microtubules. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy with seizures and severe developmental delays. The gene shows high constraint against loss-of-function variants (pLI = 1.00), indicating intolerance to haploinsufficiency in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.84

Clinical Summary— DYNLRB2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — 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?

1.84LOEUF

pLI 0.000

Z-score -0.24

OE 1.11 (0.59–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.92Z-score

OE missense 1.35 (1.12–1.65)

72 obs / 53.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.59–1.84)

0≤0.351.4

Missense OE?1.35 (1.12–1.65)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 6 / 5.4Missense obs/exp: 72 / 53.2Syn Z: -0.54

This gene — mechanism propensity

0.7230th %ile

GOF

0.6540th %ile

LOF

0.3454th %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.