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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ELAVL4
ELAV like RNA binding protein 4
Chromosome 1 · 1p33-p32.3
NCBI Gene: 1996Ensembl: ENSG00000162374.18HGNC: HGNC:3315UniProt: A0A0R4J2E6
77PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of 3'-UTR-mediated mRNA stabilizationpoly(A) bindingmRNA 3'-UTR AU-rich region bindingpre-mRNA intronic pyrimidine-rich bindingsmoking initiationobesityneurodegenerative diseaseAbnormality of the skeletal system
✦AI Summary

ELAVL4 (HuD) is a neuron-enriched RNA-binding protein that post-transcriptionally regulates mRNA stability, alternative splicing, and translation 1. The protein binds AU-rich elements (AREs) in the 3' untranslated regions (3'UTR) of target mRNAs including GAP43, VEGF, and ACHE, decreasing mRNA deadenylation and protecting transcripts from decay 23. ELAVL4 plays a critical role in neuron-specific RNA processing, promoting neural progenitor differentiation and contributing to learning, memory, neurite outgrowth, and dendritic development 45. ELAVL4 dysfunction is implicated in multiple neurodegenerative diseases. In Alzheimer's disease, ELAVL4 knockout increases pathological APP isoforms and phosphorylated tau, while overexpression reduces extracellular amyloid-beta levels 6. In amyotrophic lateral sclerosis (ALS), FUS mutations increase HuD levels, causing overstabilization of axonal growth transcripts NRN1 and GAP43 7, and HuD overexpression impairs neuromuscular junctions and induces motoneuron apoptosis 8. In frontotemporal dementia, ELAVL4 upregulation precedes glutamatergic neuronal loss 9. Additionally, ELAVL4 regulates neuronal dsRNA levels through 3'UTR length control, maintaining antiviral immunity while preventing pathological neuroinflammation 10. Beyond neurology, ELAVL4 stabilizes oncogenic lncRNAs in small cell lung cancer 11. These findings establish ELAVL4 as a critical neuronal RBP with therapeutic potential across multiple disease contexts.

Sources cited
1
ELAVL4 (HuD) is a neuron-enriched RNA-binding protein that post-transcriptionally regulates mRNA stability, alternative splicing, and translation .
PMID: 23861535
2
In Alzheimer's disease, ELAVL4 knockout increases pathological APP isoforms and phosphorylated tau, while overexpression reduces extracellular amyloid-beta levels .
PMID: 35843356
3
In amyotrophic lateral sclerosis (ALS), FUS mutations increase HuD levels, causing overstabilization of axonal growth transcripts NRN1 and GAP43 , and HuD overexpression impairs neuromuscular junctions and induces motoneuron apoptosis .
PMID: 34471224
4
In amyotrophic lateral sclerosis (ALS), FUS mutations increase HuD levels, causing overstabilization of axonal growth transcripts NRN1 and GAP43 , and HuD overexpression impairs neuromuscular junctions and induces motoneuron apoptosis .
PMID: 39511225
5
In frontotemporal dementia, ELAVL4 upregulation precedes glutamatergic neuronal loss .
PMID: 34314701
6
Additionally, ELAVL4 regulates neuronal dsRNA levels through 3'UTR length control, maintaining antiviral immunity while preventing pathological neuroinflammation .
PMID: 37862432
7
Beyond neurology, ELAVL4 stabilizes oncogenic lncRNAs in small cell lung cancer .
PMID: 37676718
Disease Associationsⓘ20
smoking initiationOpen Targets
0.44Moderate
obesityOpen Targets
0.41Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
Abnormality of the skeletal systemOpen Targets
0.36Weak
attention deficit hyperactivity disorderOpen Targets
0.35Weak
substance abuseOpen Targets
0.31Weak
smoking behaviorOpen Targets
0.31Weak
dislocationOpen Targets
0.30Weak
HypercalcemiaOpen Targets
0.30Weak
cannabis dependenceOpen Targets
0.29Weak
smoking cessationOpen Targets
0.29Weak
major depressive disorderOpen Targets
0.25Weak
Peyronie diseaseOpen Targets
0.24Weak
schizophreniaOpen Targets
0.23Weak
anorexia nervosaOpen Targets
0.15Weak
major depressive episodeOpen Targets
0.15Weak
substance-related disorderOpen Targets
0.13Weak
pathological myopiaOpen Targets
0.12Weak
atrial fibrillationOpen Targets
0.12Weak
myopiaOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDCP2Protein interaction89%HIVEP3Protein interaction80%USP24Protein interaction79%IGF2BP1Protein interaction76%NXF1Protein interaction74%NOVA1Protein interaction72%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
0%
Liver
0%
Ovary
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
ELAVL4CDCP2HIVEP3USP24IGF2BP1NXF1NOVA1
PROTEIN STRUCTURE
Preparing viewer…
PDB1FXL · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.14Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.03 [0.01–0.14]
RankingsWhere ELAVL4 stands among ~20K protein-coding genes
  • #6,151of 20,598
    Most Researched77
  • #156of 17,882
    Most Constrained (LOEUF)0.14 · top 1%
Genes detectedELAVL4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids.
PMID: 34314701
Cell · 2021
1.00
2
Long 3'UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation.
PMID: 37862432
Sci Immunol · 2023
0.90
3
HuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models.
PMID: 39511225
Nat Commun · 2024
0.80
4
Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction.
PMID: 23861535
RNA · 2013
0.70
5
RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons.
PMID: 35843356
Prog Neurobiol · 2022
0.60