RAB11B

Chr 19AD

RAB11B, member RAS oncogene family

Also known as: H-YPT3, NDAGSCW

NCBI Gene: 9230ENSG00000185236UniProt: Q15907OMIM: 604198

The protein regulates recycling endosome membrane trafficking and exocytotic/endocytotic pathways. Dominant-negative mutations cause autosomal dominant neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter. The pathogenic mechanism involves dominant-negative effects that disrupt normal endosomal trafficking functions.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.641 OMIM phenotype
Clinical Summary— RAB11B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 79 VUS of 271 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
0.64LOEUF
pLI 0.444
Z-score 2.31
OE 0.20 (0.08–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.48Z-score
OE missense 0.44 (0.36–0.53)
67 obs / 153.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.20 (0.08–0.64)
0≤0.351.4
Missense OE0.44 (0.36–0.53)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 2 / 9.8Missense obs/exp: 67 / 153.6Syn Z: -0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRAB11B-related intellectual disabilityOTHERAD
DN
0.76top 25%
GOF
0.6832th %ile
LOF
0.3746th %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 · 1 literature citation
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.

Literature Evidence

DNLamers et al. (2017) concluded that the mutations act in a dominant-negative manner to alter GDP/GTP binding, thus inactivating the protein and causing alterations in binding to certain guanine nucleotide exchange factors (GEFs), as well as protein mislocalization, which may have additional adverse PMID:29106825

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

271 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic6
VUS79
Likely Benign136
Benign34
Conflicting7
5
Pathogenic
6
Likely Pathogenic
79
VUS
136
Likely Benign
34
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
4
0
5
Likely Pathogenic
0
5
1
0
6
VUS
5
63
11
0
79
Likely Benign
1
15
47
73
136
Benign
0
3
22
9
34
Conflicting
—7
Total6878582267

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB11B · 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 5 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