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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RBFOX3
RNA binding fox-1 homolog 3
Chromosome 17 · 17q25.3
NCBI Gene: 146713Ensembl: ENSG00000167281.20HGNC: HGNC:27097UniProt: A0A8I5KWJ3
47PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmnucleuscytoplasmregulation of alternative mRNA splicing, via spliceosomeneurodegenerative diseaseRolandic epilepsyself-limited epilepsy with centrotemporal spikesAbnormality of the skeletal system
✦AI Summary

RBFOX3 is an RNA-binding protein that functions as a pre-mRNA alternative splicing regulator in the nervous system 123. The protein localizes to the nucleoplasm and cytoplasm, where it regulates alternative splicing of RBFOX2 to enhance the production of mRNA species targeted for nonsense-mediated decay 1. RBFOX3 serves as a neuronal marker used to identify and characterize neuronal populations and their dynamic transcriptome profiles 45. Recent large-scale genomic analysis identified RBFOX3 as associated with epilepsy susceptibility, representing a novel disease-gene relationship discovered through rare variant burden analysis in the 100,000 Genomes Project 6. The gene plays roles in nervous system development and maintains neuronal integrity across multiple pathological contexts, including traumatic brain injury, chr17 pain with comorbid anxiety, and neurodegenerative conditions 378. RBFOX3's expression patterns help distinguish neuronal subpopulations with distinct functional states, particularly in pancreatic islet gamma cells 4. These findings establish RBFOX3 as an important regulator of neuronal function with emerging clinical relevance to neurological and neuropsychiatric disorders.

Sources cited
1
RBFOX3 is used as a neuronal marker (NeuN) to identify neurons in various pathological conditions
PMID: 37204119
2
RBFOX3 serves as a neuronal marker in stroke models to assess neuronal survival and microglial activation
PMID: 33317392
3
RBFOX3 is associated with epilepsy as a novel disease-gene discovery from rare variant analysis in 100,000 Genomes Project
PMID: 40011789
4
RBFOX3 is used as a neuronal marker to identify neurons affected by lysosomal membrane permeabilization in traumatic brain injury
PMID: 31238788
5
RBFOX3 is identified as a novel marker gene selectively expressed in pancreatic gamma cells with distinct gene expression patterns
PMID: 37127706
6
RBFOX3 is used as a neuronal marker to identify neuronal populations with impaired macroautophagy in chronic pain models
PMID: 38522078
7
RBFOX3 is used as a neuronal marker to assess neurodegeneration in models of poly-G-induced neurodegeneration
PMID: 39936620
8
RBFOX3 is used as a neuronal marker with HSP60 to assess neuronal mitochondrial quantity in Alzheimer's disease models
PMID: 39520951
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
Rolandic epilepsyOpen Targets
0.34Weak
self-limited epilepsy with centrotemporal spikesOpen Targets
0.33Weak
Abnormality of the skeletal systemOpen Targets
0.31Weak
autosomal dominant compelling helio-ophthalmic outburst syndromeOpen Targets
0.31Weak
response to paracetamolOpen Targets
0.30Weak
Dupuytren ContractureOpen Targets
0.27Weak
liver diseaseOpen Targets
0.26Weak
thrombophiliaOpen Targets
0.25Weak
chronic laryngitisOpen Targets
0.25Weak
nephrotic syndromeOpen Targets
0.24Weak
mixed connective tissue diseaseOpen Targets
0.23Weak
hypertrophic cardiomyopathyOpen Targets
0.23Weak
cardiac arrestOpen Targets
0.23Weak
kidney diseaseOpen Targets
0.22Weak
response to angiotensin-converting enzyme inhibitorOpen Targets
0.20Weak
generalised epilepsyOpen Targets
0.19Weak
ArthropathyOpen Targets
0.19Weak
body weight gainOpen Targets
0.19Weak
Respiratory insufficiencyOpen Targets
0.18Weak
Pathogenic Variants1
NM_001350451.2(RBFOX3):c.1002C>A (p.Tyr334Ter)Pathogenic
Self-limited epilepsy with centrotemporal spikes
☆☆☆☆2017→ Residue 334
View on ClinVar ↗
Related Genes
GAD1Protein interaction97%CNPProtein interaction93%MAP2Protein interaction93%S100BProtein interaction93%NESProtein interaction93%ACTBProtein interaction93%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
17%
Ovary
5%
Liver
2%
Lung
2%
Heart
0%
Gene Interaction Network
Click a node to explore
RBFOX3GAD1CNPMAP2S100BNESACTB
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt A6NFN3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.60LoF Tolerant
pLIⓘ
0.60Intermediate
Observed/Expected LoF0.38 [0.25–0.60]
RankingsWhere RBFOX3 stands among ~20K protein-coding genes
  • #9,265of 20,598
    Most Researched47
  • #5,122of 5,498
    Most Pathogenic Variants1
  • #4,180of 17,882
    Most Constrained (LOEUF)0.60 · top quartile
Genes detectedRBFOX3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.
PMID: 37204119
Autophagy · 2023
1.00
2
PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery.
PMID: 33317392
Autophagy · 2021
0.90
3
Rare disease gene association discovery in the 100,000 Genomes Project.
PMID: 40011789
Nature · 2025
0.80
4
PLA2G4A/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma.
PMID: 31238788
Autophagy · 2020
0.70
5
Single-nucleus RNA sequencing of human pancreatic islets identifies novel gene sets and distinguishes β-cell subpopulations with dynamic transcriptome profiles.
PMID: 37127706
Genome Med · 2023
0.60