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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RABEP1
rabaptin, RAB GTPase binding effector protein 1
Chromosome 17 · 17p13.2
NCBI Gene: 9135Ensembl: ENSG00000029725.18HGNC: HGNC:17677UniProt: B4DMM4
120PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
endocytic vesicleprotein bindingprotein-containing complexvesicle-mediated transportAlzheimer diseaseplacenta praeviapancreatic ductal adenocarcinomanodular melanoma
✦AI Summary

RABEP1 (rabaptin, RAB GTPase binding effector protein 1) is a Rab effector protein that functions as a linker between gamma-adaptin and RAB4A/RAB5A, mediating endocytic membrane fusion and recycling endosome trafficking. RABEP1 forms complexes with RABGEF1 to stimulate nucleotide exchange on RAB5A and regulates the trafficking of ion channels like KCNH1 to the cell membrane. The protein operates through a conserved Rab4/Rab5 binding domain essential for its function 1. Mechanistically, RABEP1 drives endosomal recycling and actin polymerization at the leading edge of cells through Rac activation, with ITSN2L acting as a negative regulator by promoting RABEP1 degradation 2. The protein exists as multiple splice variants 3. Clinically, RABEP1 dysregulation contributes to multiple diseases. In chr17 pancreatitis, RABEP1-mediated endocytosis of trypsinogen promotes pancreatic stellate cell activation 4. In neutrophils, RABEP1 is essential for cell motility and chemotaxis 1. RABEP1 represents a pleiotropic gene linked to schizophrenia and inflammatory bowel disease susceptibility 5. In Alzheimer's disease, RABEP1 mutations (p.R845W) dysregulate endocytosis and exacerbate amyloid-β accumulation 6, with the protein identified as a predictive biomarker across disease stages 7. RABEP1 also inhibits autophagy in atherosclerosis through miR-224-3p regulation 8.

Sources cited
1
RABEP1 drives endosomal recycling, Rac activation, and leading-edge actin polymerization; contains essential Rab4/Rab5 binding domain required for neutrophil motility
PMID: 40463167
2
ITSN2L negatively regulates RABEP1 by promoting its degradation and repressing RABEP1-enhanced endosome aggregation
PMID: 26633357
3
RABEP1 exists as multiple splice variants (Rabaptin-5, Rabaptin-5delta, Rabaptin-5gamma) encoded by the RAB5EP gene
PMID: 12119113
4
RABEP1 mediates trypsinogen endocytosis in pancreatic stellate cells, promoting their activation in chronic pancreatitis
PMID: 36008957
5
RABEP1 is a pleiotropic gene identified in cross-trait analysis of schizophrenia and inflammatory bowel disease with shared genetic basis
PMID: 38563283
6
RABEP1 p.R845W mutation dysregulates endocytosis and exacerbates amyloid-β accumulation in Alzheimer's disease; linked to cognitive decline and brain atrophy
PMID: 39713882
7
RABEP1 identified as predictive biomarker for Alzheimer's disease classification across disease stages
PMID: 36776048
8
RABEP1 targeted by miR-224-3p, which mediates LINC01235-induced autophagy inhibition in atherosclerosis
PMID: 39316662
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.33Weak
placenta praeviaOpen Targets
0.22Weak
pancreatic ductal adenocarcinomaOpen Targets
0.19Weak
cecum adenocarcinomaOpen Targets
0.18Weak
colon adenocarcinomaOpen Targets
0.18Weak
cutaneous melanomaOpen Targets
0.18Weak
Duodenal AdenocarcinomaOpen Targets
0.18Weak
esophageal adenocarcinomaOpen Targets
0.18Weak
gliomaOpen Targets
0.18Weak
head and neck squamous cell carcinomaOpen Targets
0.18Weak
Hepatobiliary NeoplasmOpen Targets
0.18Weak
lobular breast carcinomaOpen Targets
0.18Weak
nodular melanomaOpen Targets
0.18Weak
oral squamous cell carcinomaOpen Targets
0.18Weak
ovarian serous adenocarcinomaOpen Targets
0.18Weak
papillary thyroid carcinomaOpen Targets
0.18Weak
rectal adenocarcinomaOpen Targets
0.18Weak
skin carcinomaOpen Targets
0.18Weak
thyroid carcinomaOpen Targets
0.18Weak
urinary bladder carcinomaOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RAB5BProtein interaction100%GGA3Protein interaction99%MON1AProtein interaction97%GAPVD1Protein interaction95%RBSNProtein interaction94%AP1G1Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Heart
95%
Liver
45%
Lung
42%
Ovary
42%
Bone Marrow
28%
Gene Interaction Network
Click a node to explore
RABEP1RAB5BGGA3MON1AGAPVD1RBSNAP1G1
PROTEIN STRUCTURE
Preparing viewer…
PDB1P4U · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.49Moderately Constrained
pLIⓘ
0.96Intolerant
Observed/Expected LoF0.38 [0.29–0.49]
RankingsWhere RABEP1 stands among ~20K protein-coding genes
  • #3,936of 20,598
    Most Researched120 · top quartile
  • #2,903of 17,882
    Most Constrained (LOEUF)0.49 · top quartile
Genes detectedRABEP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PMID: 33712570
1.00
2
The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation.
PMID: 36008957
Biomolecules · 2022
0.90
3
ITSN2L Interacts with and Negatively Regulates RABEP1.
PMID: 26633357
Int J Mol Sci · 2015
0.80
4
Multiple Rabaptin-5-like transcripts.
PMID: 12119113
Gene · 2002
0.70
5
LPI-GPR55 promotes endothelial cell activation and inhibits autophagy through inducing LINC01235 expression.
PMID: 39316662
Ann Med · 2024
0.60