HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RBSN
rabenosyn, RAB effector
Chromosome 3 Β· 3p25.1
NCBI Gene: 64145Ensembl: ENSG00000131381.14HGNC: HGNC:20759UniProt: A8K5H3
65PubMed Papers
22Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingphosphatidylinositol-3-phosphate bindingearly endosome to Golgi transportGolgi to lysosome transportKariminejad neurodevelopmental syndromemyelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalitiesinsomniaGenu valgum
✦AI Summary

RBSN (rabenosyn) is a conserved Rab4/Rab5 effector protein that functions as a critical regulator of early endocytic membrane trafficking and cargo sorting. Structurally, RBSN contains a FYVE domain that binds phosphatidylinositol 3-phosphate (PtdInsP3), enabling its translocation to early endosomes where it mediates homotypic endosome fusion and fusion with clathrin-coated vesicles 1. RBSN bridges interactions between Rab5 and the SNARE fusion machinery through Vps45, linking small GTPase activation to membrane fusion events 2. The protein functions as part of the FERARI tethering platform that coordinates Rab11-dependent recycling pathways at sorting endosomes, combining fusion activity with membrane fission through interactions with VPS45 and EHD1 3. Beyond endosomal recycling, RBSN promotes transferrin receptor recycling to the plasma membrane and lysosomal trafficking of cathepsin D from the Golgi 1. Recently, RBSN was identified as a GAP protein that suppresses non-small cell lung cancer metastasis by inhibiting CDC42 activity and filopodia formation 4. Mutations in RBSN cause distinct Mendelian disorders: separation-of-function FYVE domain variants impair PI3P binding and delay endosomal maturation without affecting recycling, causing muscle weakness and ophthalmoplegia 1, while other mutations result in intractable seizures and multi-organ dysfunction through defective endocytic trafficking 5.

Sources cited
1
RBSN FYVE domain binds PI3P and mediates endosome fusion; mutations cause endosomal maturation delay affecting lysosomal degradation
PMID: 35652444
2
RBSN is a Rab5 effector that bridges Rab5 to Vps45 and SNARE machinery on early endosomes
PMID: 18685079
3
RBSN is part of the FERARI tethering platform involved in Rab11-dependent endocytic recycling
PMID: 31988382
4
RBSN acts as a GAP protein inhibiting CDC42 activity to suppress lung cancer metastasis
PMID: 39075137
5
RBSN mutations cause intractable seizures, developmental delay, and impaired transferrin endocytosis
PMID: 25233840
Disease Associationsβ“˜22
Kariminejad neurodevelopmental syndromeOpen Targets
0.52Moderate
myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalitiesOpen Targets
0.45Moderate
insomniaOpen Targets
0.24Weak
benign chondrogenic neoplasmOpen Targets
0.23Weak
Genu valgumOpen Targets
0.23Weak
hypertrophic cardiomyopathyOpen Targets
0.23Weak
Genu varumOpen Targets
0.23Weak
phimosisOpen Targets
0.09Suggestive
paraphimosisOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.04Suggestive
protozoa infectious diseaseOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
malariaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
juvenile dermatomyositisOpen Targets
0.01Suggestive
lymph node metastatic carcinomaOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
gliomaOpen Targets
0.00Suggestive
Kariminejad neurodevelopmental syndromeUniProt
Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalitiesUniProt
Pathogenic Variants3
NM_022340.4(RBSN):c.289G>C (p.Gly97Arg)Pathogenic
Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities
β˜†β˜†β˜†β˜†2025β†’ Residue 97
NM_022340.4(RBSN):c.547G>A (p.Gly183Arg)Pathogenic
Kariminejad neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2025β†’ Residue 183
NM_022340.4(RBSN):c.538C>G (p.Arg180Gly)Pathogenic
Kariminejad neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2025β†’ Residue 180
View on ClinVar β†—
Related Genes
STX6Protein interaction100%RAB4AProtein interaction100%RABEP1Protein interaction94%RABGEF1Protein interaction94%RAB22AProtein interaction94%RAB5CProtein interaction87%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
85%
Heart
67%
Ovary
59%
Liver
42%
Lung
42%
Gene Interaction Network
Click a node to explore
RBSNSTX6RAB4ARABEP1RABGEF1RAB22ARAB5C
PROTEIN STRUCTURE
Preparing viewer…
PDB1Z0J Β· 1.32 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.74LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.56 [0.42–0.74]
RankingsWhere RBSN stands among ~20K protein-coding genes
  • #7,202of 20,598
    Most Researched65
  • #4,039of 5,498
    Most Pathogenic Variants3
  • #5,824of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedRBSN
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
RABENOSYN separation-of-function mutations uncouple endosomal recycling from lysosomal degradation, causing a distinct Mendelian disorder.
PMID: 35652444
Hum Mol Genet Β· 2022
1.00
2
Rabenosyn-5 suppresses non-small cell lung cancer metastasis via inhibiting CDC42 activity.
PMID: 39075137
Cancer Gene Ther Β· 2024
0.90
3
Identification of New Interactions between Endolysosomal Tethering Factors.
PMID: 33781757
J Mol Biol Β· 2021
0.80
4
FERARI is required for Rab11-dependent endocytic recycling.
PMID: 31988382
Nat Cell Biol Β· 2020
0.70
5
Regulation of early endosomal entry by the Drosophila tumor suppressors Rabenosyn and Vps45.
PMID: 18685079
Mol Biol Cell Β· 2008
0.60