DYNLRB2

Chr 16

dynein light chain roadblock-type 2

Also known as: DNCL2B, DNLC2B, ROBLD2

NCBI Gene: 83657ENSG00000168589UniProt: Q8TF09OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.84
Clinical Summary— DYNLRB2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 40 VUS of 82 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE1.11 (0.59–1.84)
0≤0.351.4
Missense OE1.35 (1.12–1.65)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 6 / 5.4Missense obs/exp: 72 / 53.2Syn Z: -0.54
DN
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.

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic5
VUS40
Benign1
34
Pathogenic
5
Likely Pathogenic
40
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
5
0
5
VUS
0
28
12
0
40
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total02851180

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DYNLRB2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients