RAB26

Chr 16

RAB26, member RAS oncogene family

RAB26 encodes a small GTPase that regulates intracellular vesicle trafficking and transport of specific proteins from the Golgi to the cell membrane, and plays a role in secretory granule maturation and secretion in stomach and salivary gland cells. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF 1.589), and no clear Mendelian diseases have been established from RAB26 mutations. Based on current evidence, RAB26 variants are unlikely to cause monogenic pediatric neurological disorders.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.59
Clinical SummaryRAB26
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.59LOEUF
pLI 0.000
Z-score 0.03
OE 0.99 (0.631.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.81Z-score
OE missense 1.20 (1.051.37)
156 obs / 130.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.99 (0.631.59)
00.351.4
Missense OE1.20 (1.051.37)
00.61.4
Synonymous OE1.31
01.21.6
LoF obs/exp: 12 / 12.1Missense obs/exp: 156 / 130.0Syn Z: -1.81
DN
0.82top 10%
GOF
0.77top 25%
LOF
0.3258th %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

RAB26 · 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.

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Clinical Literature
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