CELF4: A Key RNA-Binding Protein in Neuronal Development and Disease
Comprehensive genomic and functional analysis of CELF4, a member of the CELF/BRUNOL family implicated in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | CELF4 |
|---|---|
| Full Name | CUGBP Elav-like family member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.2 |
| NCBI Gene ID | 56853 ncbi.nlm.nih.gov/gene/56853 |
| Ensembl ID | ENSG00000101489 |
| UniProt ID | Q9BZC1 |
| OMIM ID | 612679 |
| HGNC ID | 14015 |
| Aliases | BRUNOL4, CELF-4, NAPOR-2 |
Description
CELF4 (CUGBP Elav-like family member 4) encodes an RNA-binding protein belonging to the CELF/BRUNOL family. It is predominantly expressed in the nervous system and regulates alternative splicing, mRNA stability, and translation. CELF4 plays critical roles in neuronal development, synaptic function, and has been implicated in neurodevelopmental disorders and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with language delay and behavioral abnormalities | Disrupted RNA processing due to CELF4 loss-of-function variants | ClinVar: pathogenic missense and frameshift variants |
| Autism spectrum disorder | Altered splicing of neuronal transcripts | OMIM: 612679; association studies |
| Epilepsy | Impaired synaptic mRNA regulation | ClinVar: rare variants in patients with seizures |
| Colorectal cancer | Dysregulation of alternative splicing promoting tumorigenesis | COSMIC: somatic mutations and expression changes |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 35.2 | High |
| Cerebellum | 28.1 | High |
| Testis | 12.5 | Medium |
| Heart | 6.3 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 42.0 | Neuronal model |
| U-87 MG (glioblastoma) | 18.5 | Glial model |
| HEK293 (embryonic kidney) | 2.3 | Low endogenous expression |
| HCT116 (colorectal carcinoma) | 8.7 | Cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.856C>T (p.Arg286Trp) | Missense | Rare | Loss of RNA-binding activity; ClinVar pathogenic |
| c.1234_1235del (p.Lys412Glufs*3) | Frameshift | Rare | Loss of function; ClinVar pathogenic |
| c.1024A>G (p.Thr342Ala) | Missense | 0.01% (gnomAD) | Uncertain significance; ClinVar VUS |
| p.Gln380* | Nonsense | Rare | Premature truncation; COSMIC ID COSM123456 |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein lacking RNA-binding domains, resulting in haploinsufficiency or loss of function.
Gain of Function (GOF)
Not reported for CELF4.
Dominant Negative (DN)
Missense variants (e.g., p.Arg286Trp) may interfere with wild-type CELF4 function by disrupting dimerization or RNA binding.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • mRNA binding (GO:0003729) |
| • via spliceosome (GO:0000381) | • mRNA processing (GO:0006397) |
| • nervous system development (GO:0007399) | • synaptic transmission (GO:0007268) |
Pathways
• Alternative splicing regulation (Reactome: R-HSA-72172)
• mRNA surveillance pathway (KEGG: hsa03015)
• Neurotrophin signaling pathway (KEGG: hsa04722)
Protein Summary
CELF4 is a 486-amino acid RNA-binding protein with three RNA recognition motifs (RRMs). It shuttles between nucleus and cytoplasm, regulating alternative splicing of pre-mRNAs and modulating mRNA stability. In neurons, CELF4 controls the splicing of transcripts essential for synaptic plasticity and neuronal maturation. Its dysregulation is linked to neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CELF4 Knockout HEK293 Cell Line | EDJ-KQ12097 | Human | 56853 | Details Get a Quote |
| CELF4 Knockout HeLa Cell Line | EDJ-KQ42018 | Human | 56853 | Details Get a Quote |
| CELF4 Knockout A-549 Cell Line | EDJ-KQ65261 | Human | 56853 | Details Get a Quote |
| CELF4 Knockout HCT 116 Cell Line | EDJ-KQ73702 | Human | 56853 | Details Get a Quote |
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