RAB25

Chr 1

RAB25, member RAS oncogene family

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). RAB25 regulates epithelial cell differentiation, proliferation and survival, thereby playing key roles in tumorigenesis (PubMed:17925226). Promotes invasive migration of cells in which it functions to localize and maintain integrin alpha-V/beta-1 at the tips of extending pseudopodia (PubMed:17925226). Involved in the regulation of epithelial morphogenesis through the control of CLDN4 expression and localization at tight junctions (By similarity). May selectively regulate the apical recycling pathway (By similarity). Together with MYO5B regulates transcytosis (By similarity)

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.55
Clinical SummaryRAB25
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?
1.55LOEUF
pLI 0.000
Z-score 0.17
OE 0.95 (0.591.55)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.82Z-score
OE missense 0.80 (0.680.94)
106 obs / 132.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.95 (0.591.55)
00.351.4
Missense OE?0.80 (0.680.94)
00.61.4
Synonymous OE?0.99
01.21.6
LoF obs/exp: 11 / 11.6Missense obs/exp: 106 / 132.4Syn Z: 0.06

This gene — mechanism propensity

DN
0.81top 10%
GOF
0.75top 25%
LOF
0.2775th %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

RAB25 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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