Details for: CELF4

Gene ID: 56853

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CELF4

Ensembl ID: ENSG00000101489

Description: CUGBP Elav-like family member 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sst GABAergic cortical interneuron CL4023017
    CSI 44.96
    rCSI 57.96%
    PRS 95.52
  • VIP GABAergic cortical interneuron CL4023016
    CSI 43.63
    rCSI 52.12%
    PRS 94.89
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 42.57
    rCSI 52.95%
    PRS 94.11
  • sncg GABAergic cortical interneuron CL4023015
    CSI 39.18
    rCSI 63.01%
    PRS 94.91
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 37.16
    rCSI 62.38%
    PRS 95.17
  • retina horizontal cell CL0000745
    CSI 35.95
    rCSI 54.81%
    PRS 97.12
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 33.56
    rCSI 59.28%
    PRS 94.93
  • interneuron CL0000099
    CSI 32.14
    rCSI 64.53%
    PRS 96.8
  • cerebellar granule cell CL0001031
    CSI 31.09
    rCSI 45.7%
    PRS 96.18
  • amacrine cell CL0000561
    CSI 30.63
    rCSI 88.78%
    PRS 95.28
  • inhibitory interneuron CL0000498
    CSI 27.99
    rCSI 64.61%
    PRS 95.23
  • peripheral nervous system neuron CL2000032
    CSI 27.32
    rCSI 37.23%
    PRS 96.36
  • glycinergic amacrine cell CL4030028
    CSI 27
    rCSI 70.34%
    PRS 95.09
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 24.72
    rCSI 59.12%
    PRS 93.88
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 23.95
    rCSI 58.2%
    PRS 93.65
  • neuron CL0000540
    CSI 22.96
    rCSI 61.14%
    PRS 92.55
  • rod bipolar cell CL0000751
    CSI 21.09
    rCSI 37.89%
    PRS 96.47
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 20.66
    rCSI 23.86%
    PRS 95.89
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 20.32
    rCSI 44.08%
    PRS 92.93
  • GABAergic amacrine cell CL4030027
    CSI 20.26
    rCSI 69.39%
    PRS 92.63
  • enteroendocrine cell CL0000164
    CSI 20.23
    rCSI 27.64%
    PRS 97.29
  • retinal ganglion cell CL0000740
    CSI 19.83
    rCSI 43.8%
    PRS 94.76
  • glutamatergic neuron CL0000679
    CSI 19.77
    rCSI 40.63%
    PRS 92.72
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 19.6
    rCSI 57.86%
    PRS 98.29
  • L6b glutamatergic cortical neuron CL4023038
    CSI 19.56
    rCSI 61.11%
    PRS 95.17
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 18.72
    rCSI 58.54%
    PRS 95.55
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 18.67
    rCSI 23.97%
    PRS 97.45
  • pancreatic D cell CL0000173
    CSI 18.6
    rCSI 18.29%
    PRS 98.3
  • cerebral cortex endothelial cell CL1001602
    CSI 17.95
    rCSI 31.05%
    PRS 96.79
  • Mueller cell CL0000636
    CSI 16.48
    rCSI 37.62%
    PRS 96.32
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 16.13
    rCSI 53.01%
    PRS 93.32
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 16.02
    rCSI 60.55%
    PRS 94.5
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 14.96
    rCSI 53.84%
    PRS 93.97
  • neural cell CL0002319
    CSI 14.94
    rCSI 56.37%
    PRS 92.46
  • OFF-bipolar cell CL0000750
    CSI 14.9
    rCSI 20.37%
    PRS 97.33
  • H1 horizontal cell CL0004217
    CSI 14.62
    rCSI 57.92%
    PRS 95.13
  • epithelial cell CL0000066
    CSI 14.03
    rCSI 21.57%
    PRS 93.1
  • cerebral cortex neuron CL0010012
    CSI 13.89
    rCSI 56.61%
    PRS 94.78
  • vascular leptomeningeal cell CL4023051
    CSI 13.87
    rCSI 24.31%
    PRS 97.04
  • glial cell CL0000125
    CSI 13
    rCSI 49.49%
    PRS 95.73
  • pancreatic A cell CL0000171
    CSI 12.86
    rCSI 13.47%
    PRS 98.41
  • retinal bipolar neuron CL0000748
    CSI 11.46
    rCSI 21.45%
    PRS 95.54
  • astrocyte of the cerebral cortex CL0002605
    CSI 11.11
    rCSI 24.91%
    PRS 94.96
  • H2 horizontal cell CL0004218
    CSI 10.99
    rCSI 54.65%
    PRS 95.67
  • lung neuroendocrine cell CL1000223
    CSI 10.75
    rCSI 15.9%
    PRS 97.9
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 10.62
    rCSI 62.53%
    PRS 94.66
  • GABAergic neuron CL0000617
    CSI 10.45
    rCSI 35.02%
    PRS 92.39
  • ON-bipolar cell CL0000749
    CSI 10.25
    rCSI 15.23%
    PRS 97.51
  • serotonergic neuron CL0000850
    CSI 9.51
    rCSI 42.48%
    PRS 90.99
  • central nervous system neuron CL2000029
    CSI 8.71
    rCSI 64.03%
    PRS 95.57
  • neural progenitor cell CL0011020
    CSI 8.58
    rCSI 37.76%
    PRS 93.15
  • dopaminergic neuron CL0000700
    CSI 8.54
    rCSI 48.26%
    PRS 93.81
  • retinal cone cell CL0000573
    CSI 8.22
    rCSI 13.24%
    PRS 95.44
  • midbrain dopaminergic neuron CL2000097
    CSI 7.87
    rCSI 50.42%
    PRS 95.42
  • starburst amacrine cell CL0004232
    CSI 6.93
    rCSI 58.35%
    PRS 91.2
  • type B pancreatic cell CL0000169
    CSI 6.88
    rCSI 15.22%
    PRS 98
  • diffuse bipolar 2 cell CL4033028
    CSI 6.41
    rCSI 49.66%
    PRS 94.25
  • diffuse bipolar 3b cell CL4033030
    CSI 6.18
    rCSI 41.04%
    PRS 94.59
  • medium spiny neuron CL1001474
    CSI 5.23
    rCSI 45.04%
    PRS 95.2
  • Bergmann glial cell CL0000644
    CSI 5.04
    rCSI 6.9%
    PRS 95.46
  • diffuse bipolar 6 cell CL4033032
    CSI 4.42
    rCSI 23.22%
    PRS 93.36
  • OFFx cell CL4033036
    CSI 3.84
    rCSI 18.04%
    PRS 92.97
  • GABAergic interneuron CL0011005
    CSI 3.74
    rCSI 58.9%
    PRS 97.98
  • cerebellar neuron CL1001611
    CSI 3.4
    rCSI 29.9%
    PRS 92.39
  • invaginating midget bipolar cell CL4033034
    CSI 3.08
    rCSI 18.18%
    PRS 93.88
  • cerebral cortex pyramidal neuron CL4023111
    CSI 3.06
    rCSI 18.82%
    PRS 97.83
  • direct pathway medium spiny neuron CL4023026
    CSI 2.78
    rCSI 66.53%
    PRS 92.91
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.75
    rCSI 66.31%
    PRS 92.53
  • Cajal-Retzius cell CL0000695
    CSI 2.69
    rCSI 21.11%
    PRS 98.02
  • ON midget ganglion cell CL4033046
    CSI 2.68
    rCSI 54.52%
    PRS 94.29
  • OFF midget ganglion cell CL4033047
    CSI 2.65
    rCSI 53.96%
    PRS 94.38
  • pancreatic PP cell CL0002275
    CSI 2.64
    rCSI 10.51%
    PRS 98.01
  • neuroplacodal cell CL0000032
    CSI 2.61
    rCSI 24.11%
    PRS 95.8
  • flat midget bipolar cell CL4033033
    CSI 2.54
    rCSI 18.13%
    PRS 93.65
  • diffuse bipolar 1 cell CL4033027
    CSI 2.24
    rCSI 16.84%
    PRS 92.64
  • neuroendocrine cell CL0000165
    CSI 1.57
    rCSI 6.09%
    PRS 98.23
  • cone retinal bipolar cell CL0000752
    CSI 1.26
    rCSI 16.41%
    PRS 95.12
  • enteric neuron CL0007011
    CSI 1.02
    rCSI 15.04%
    PRS 97.96

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CELF4](/details-gene/56853) (CUGBP Elav-like family member 4) is a protein-coding gene that encodes a member of the CELF family of RNA-binding proteins. These proteins are known to play crucial roles in post-transcriptional gene regulation, including the control of alternative mRNA splicing and translation ([Link](https://doi.org/10.1128/mcb.21.4.1285-1296.2001)). Expression data reveals that [CELF4](/details-gene/56853) is a highly specific marker for neuronal cell types, showing exceptionally high significance in various subtypes of GABAergic cortical interneurons, such as [sst GABAergic cortical interneuron](/details-cell/CL4023017) and [VIP GABAergic cortical interneuron](/details-cell/CL4023016). Its functional annotations link it directly to mRNA processing within the nucleus and cytoplasm, as well as to specialized roles in postsynaptic function and embryonic development, highlighting its importance in establishing and maintaining neuronal identity and function. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [CELF4](/details-gene/56853) establishes it as a gene with a highly specialized function within the central nervous system. Its expression is most significant in a diverse array of inhibitory neurons, with the highest Cell Significance Index (CSI) scores observed in cortical interneuron subtypes, including [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 44.96), [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 43.63), and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 42.57). Beyond these specific cortical interneurons, [CELF4](/details-gene/56853) also demonstrates high significance in other key neuronal populations. These include cells of the retina, such as [retina horizontal cell](/details-cell/CL0000745) and [amacrine cell](/details-cell/CL0000561), as well as [cerebellar granule cell](/details-cell/CL0001031) and various glutamatergic neurons. This highly restricted expression pattern, concentrated almost exclusively within neuronal lineages, suggests that [CELF4](/details-gene/56853) is not a general housekeeping gene but rather a critical factor for defining the specific molecular and functional characteristics of these specialized neural cell types. ## Pathways and Molecular Function The function of [CELF4](/details-gene/56853) is intrinsically tied to its role as an RNA-binding protein. Its molecular functions are dominated by its ability to bind RNA, including [mRNA binding](/details-go/GO:0003729) and [pre-mRNA binding](/details-go/GO:0036002), which enables its primary role in post-transcriptional regulation. Consistent with this, [CELF4](/details-gene/56853) is a key regulator of [alternative mRNA splicing, via spliceosome](/details-go/GO:0000380). Research indicates it can act as both an activator ([GO:0048026](/details-go/GO:0048026)) and a repressor ([GO:0048025](/details-go/GO:0048025)) of splicing, allowing it to fine-tune the proteome in a cell-specific manner ([Link](https://doi.org/10.1093/nar/gki561)). This regulatory function is directly relevant to its neuronal expression pattern. The gene's products are found in the [nucleus](/details-go/GO:0005634) and [cytoplasm](/details-go/GO:0005737), with a specific localization to the [postsynapse](/details-go/GO:0098794). This is consistent with its annotated involvement in the negative regulation of [excitatory postsynaptic potential](/details-go/GO:0090394), suggesting that by controlling the splicing and translation of key synaptic mRNAs, [CELF4](/details-gene/56853) helps modulate synaptic strength and plasticity. Furthermore, its role in processes like [embryo development](/details-go/GO:0009792) suggests that it is vital for the correct wiring and maturation of the nervous system. ## Research Directions The highly specific expression of [CELF4](/details-gene/56853) within distinct neuronal subtypes, coupled with its known function as a splicing regulator, provides a strong foundation for targeted research into neurodevelopment and neurological disease. **Proposed Hypotheses:** 1. The unique expression of [CELF4](/details-gene/56853) across different interneuron subtypes drives distinct, cell-type-specific splicing programs that are essential for establishing their unique electrophysiological and circuit-level properties. Misregulation of this process could contribute to neurodevelopmental disorders characterized by an excitatory/inhibitory imbalance. 2. Given its localization at the [postsynapse](/details-go/GO:0098794) and its role in regulating excitatory potential, [CELF4](/details-gene/56853) may locally regulate the translation of specific mRNAs in response to synaptic activity, thereby contributing to mechanisms of learning and memory such as long-term potentiation or depression. **Experimental Approach:** To test the first hypothesis, a conditional knockout of [CELF4](/details-gene/56853) could be implemented in mice using a lineage-specific Cre driver (e.g., Pvalb-Cre or Sst-Cre). Single-cell RNA sequencing (scRNA-seq) of the targeted brain region (e.g., cortex) from knockout and wild-type animals would allow for the identification of CELF4-dependent splicing events specifically within the targeted interneuron population. Subsequent electrophysiological analysis (e.g., whole-cell patch-clamp) of these neurons would determine if the loss of [CELF4](/details-gene/56853) and the consequent changes in splicing alter their intrinsic firing properties or synaptic connectivity, directly linking its molecular function to cellular identity. **Therapeutic Potential:** As an intracellular RNA-binding protein, [CELF4](/details-gene/56853) presents a challenging target for traditional small-molecule inhibitors or biologics. However, its crucial role in regulating neuronal splicing suggests therapeutic avenues could exist for neurological diseases linked to its dysfunction. Instead of targeting [CELF4](/details-gene/56853) directly, strategies using antisense oligonucleotides (ASOs) could be developed to correct the mis-splicing of its critical downstream mRNA targets. This approach would aim to restore the normal function of key proteins disrupted by [CELF4](/details-gene/56853) haploinsufficiency or gain-of-function, representing a targeted strategy of functional restoration rather than broad inhibition.

Genular Protein ID: 192149717

Symbol: CELF4_HUMAN

Name: CUGBP Elav-like family member 4

UniProtKB Accession Codes:

Q9BZC1 Q59EN7 Q86XB9 Q8N2M6 Q9BQ96 Q9NR84 Q9NR85

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 6 EvolutionaryTrace 1 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 RefSeq 5 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11158314

Title: The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing.

PubMed ID: 11158314

DOI: 10.1128/mcb.21.4.1285-1296.2001

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10893231

Title: A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator.

PubMed ID: 10893231

DOI: 10.1074/jbc.m003083200

PubMed ID: 12438720

Title: Identification and characterization of murine Brunol4, a new member of the elav/bruno family.

PubMed ID: 12438720

DOI: 10.1159/000066619

PubMed ID: 12649496

Title: Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.

PubMed ID: 12649496

DOI: 10.1261/rna.2191903

PubMed ID: 15009664

Title: Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors.

PubMed ID: 15009664

DOI: 10.1046/j.1471-4159.2003.02232.x

PubMed ID: 14973222

Title: ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in vivo.

PubMed ID: 14973222

DOI: 10.1093/nar/gkh275

PubMed ID: 15894795

Title: Identification of CELF splicing activation and repression domains in vivo.

PubMed ID: 15894795

DOI: 10.1093/nar/gki561

PubMed ID: 16862542

Title: ETR-3 represses Tau exons 2/3 inclusion, a splicing event abnormally enhanced in myotonic dystrophy type I.

PubMed ID: 16862542

DOI: 10.1002/jnr.20980

Sequence Information:

  • Length: 486
  • Mass: 51966
  • Checksum: 17EA8A6A6752C565
  • Sequence:
    • MYIKMATLAN GQADNASLST NGLGSSPGSA GHMNGLSHSP GNPSTIPMKD HDAIKLFIGQ 
IPRNLDEKDL KPLFEEFGKI YELTVLKDRF TGMHKGCAFL TYCERESALK AQSALHEQKT 
LPGMNRPIQV KPADSESRGG SSCLRQPPSQ DRKLFVGMLN KQQSEDDVRR LFEAFGNIEE 
CTILRGPDGN SKGCAFVKYS SHAEAQAAIN ALHGSQTMPG ASSSLVVKFA DTDKERTMRR 
MQQMAGQMGM FNPMAIPFGA YGAYAQALMQ QQAALMASVA QGGYLNPMAA FAAAQMQQMA 
ALNMNGLAAA PMTPTSGGST PPGITAPAVP SIPSPIGVNG FTGLPPQANG QPAAEAVFAN 
GIHPYPAQSP TAADPLQQAY AGVQQYAGPA AYPAAYGQIS QAFPQPPPMI PQQQREGPEG 
CNLFIYHLPQ EFGDAELMQM FLPFGFVSFD NPASAQTAIQ AMNGFQIGMK RLKVQLKRPK 
DANRPY