RAB27A

Ras-related protein Rab-27A

Score: 0.548 Price: $0.55 Low Druggability Status: active Wiki: RAB27A

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

28

KG EDGES

94

DEBATES

1

3D Protein Structure

🧬 RAB27A — PDB 2OT3 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.35

Clinical Stage

Phase II

Target Class

Signaling Protein

Safety

0.40

Druggability Analysis

Drug Development0.30

Structural Tractability0.85

Target Class0.50

Safety Profile0.40

Key Metrics

PDB Structures:

11

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Preclinical

Druggability Rationale: RAB27A presents medium druggability (0.55 score) due to its GTPase activity domain and availability of 11 PDB structures at 2.0 Å resolution, which support structure-based drug design. However, the challenging kinetics of GTPase inhibition and the small GTPase protein class's inherent difficulty in targeting make this moderately challenging; Nexinhib20's preclinical status reflects the early-stage nature of this approach.

Mechanism: RAB27A inhibitors would block GTP binding or GTPase activity, preventing the recruitment of effector proteins required for vesicular trafficking and exosome biogenesis. This would reduce the release of extracellular vesicles and potentially modulate intercellular communication in disease states involving excessive exosome-mediated signaling or pathological cargo transfer.

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

Nexinhib20 (preclinical) — Rab27a inhibitor, blocks exosome secretion

Structural Data:

PDB (11) ✓AlphaFold ✓Cryo-EM —

6HUF 7OPP 7OPQ 7OPR 8P3G+6 more

UniProt: H3BS49

🧬 3D Protein Structure

🧬 RAB27A — PDB 2OT3 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

RAB27A selectivity is a significant challenge due to homology with other RAB GTPases (RAB27B, RAB3A, RAB11); off-target inhibition could disrupt alternative vesicular trafficking pathways. Structure-guided design exploiting RAB27A-specific residues and allosteric pockets may improve selectivity over closely related isoforms.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

1

Completed

7

Total Enrollment

860

By Phase

NA: 5 · PHASE1: 1 · PHASE2: 1 · Unknown: 1

Anger Control Training for Youth With Tourette Syndrome Completed

NA NCT00486551 n=26

Tourette Syndrome, Chronic Tic Disorder, Oppositional Defiant Disorder

Interventions: Anger control training

Sponsor: Yale University | Started: 2001-08

Adaptive vs. Continuous Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease Recruiting

NA NCT06909045 n=130

Deep Brain Stimulation, Parkinson Disease

Interventions: Adaptive DBS, Continue DBS

Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC | Started: 2026-01-27

Expiratory Muscle Training in Patients With Parkinson's Disease Completed

PHASE1 NCT00843739 n=90

Parkinson's Disease

Interventions: EMST - Active Treatment, sham EMST

Sponsor: University of Florida | Started: 2004-01

Study of the Follow-up of Stroke Treated With Anticoagulants Completed

Unknown NCT03292575 n=441

Stroke

Interventions: Anticoagulants

Sponsor: Centre Hospitalier Universitaire Dijon | Started: 2016-01

Early Detection and Prevention of Mild Cognitive Impairment Due to Cerebrovascular Disease Completed

NA NCT01924312 n=80

Cerebrovascular Disease, Mild Cognitive Impairment

Interventions: Heart Health Intervention

Sponsor: Gregory Jicha, 323-5550 | Started: 2013-05

Effects of Modern Board Games on Well Being in Older Adults Completed

NA NCT06306365 n=35

Executive Functions

Interventions: Modern board game-based learning

Sponsor: European University Miguel de Cervantes | Started: 2024-02-07

Treatment of Alzheimer's and Dementia With the Metabolism, Infections, Nutrition, Drug Elimination (MIND) Protocol Completed

NA NCT02260167 n=25

Alzheimer's Disease, Dementia

Interventions: A mix of natural treatments and medicati

Sponsor: Practitioners Alliance Network | Started: 2014-09

A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2) Completed

PHASE2 NCT03987295 n=33

Frontotemporal Dementia

Interventions: AL001

Sponsor: Alector Inc. | Started: 2019-09-27

Linked Hypotheses (3)

Rab27A/B-mediated exosomal tau secretion from microglia drives frontal cortex propagation at Braak I0.690

RAB27A-dependent extracellular vesicle engineering for mitochondrial cargo delivery0.674

Exosomal α-Synuclein as an Interneuronal Propagation Vector in Parkinson's Disease0.595

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (3)

JUN→RAB27ALATS2→RAB27ARAB27A→LATS2

associated with (1)

co discussed (6)

COX4I1→RAB27APRKAA1→RAB27AGJA1→RAB27ARAB27A→GAP43RAB27A→TFAM

▸ Show 1 more

TRAK1_KIF5A→RAB27A

inhibits (9)

CDKN2A→RAB27ATLR4→RAB27ATNC→RAB27ANTRK2→RAB27AWNT7A→RAB27A

▸ Show 4 more

LZTS1→RAB27ADCC→RAB27AKCNK2→RAB27ACD44→RAB27A

regulates (1)

RAB27A→RAB27B

Debate History (1)

Should RAB27A (Ras-related protein Rab-27A) be prioritized as a therapeutic targ2026-04-22