GeneBe

CELF2

protein-coding

CUGBP Elav-like family member 2, the group of RNA binding motif containing

Gene summary

Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Previous symbols:
  • CUGBP2

MANE transcript

NM_001326342.2

Inheritance

AD

ClinVar variants

P:20U:86B:8

Top phenotype

Developmental and epileptic encephalopathy 97

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr10:10,798,397-11,336,675

External References & Databases

Ensembl (ENSG00000048740)NCBI Gene (10659)OMIM (602538)HGNC:2550GenCCUniProt (O95319)AlphaFoldClinVar (CELF2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~538.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

undetermined early-onset epileptic encephalopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018614

Submitter: Orphanet

developmental and epileptic encephalopathy 97STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030453

Submitter: G2P

developmental and epileptic encephalopathy 97MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030453

Submitter: Ambry Genetics

developmental and epileptic encephalopathy 97STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030453

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 97AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33131106Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CELF2 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 50
not specifiedTotal: 37
Developmental and epileptic encephalopathy 97Total: 23
CELF2-related disorderTotal: 7
Neurodevelopmental disorderTotal: 2
Developmental and epileptic encephalopathy, 14Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001326342.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
5
clinvar
 8
missense
4
clinvar
3
clinvar
67
clinvar
3
clinvar
 77
nonsense
2
clinvar
1
clinvar
2
clinvar
 5
start loss
1
clinvar
 1
frameshift
3
clinvar
6
clinvar
7
clinvar
 16
splice donor/acceptor (+/-2bp)
1
clinvar
6
clinvar
 7
Total9118680114

Highest pathogenic variant AF is 6.884947e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 98 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001326342.2RefSeqNP_001313271.113MANE Select
ENST00000633077.2EnsemblENSP00000488690.113MANE Select
NM_001025076.2RefSeqNP_001020247.112Standard
NM_001025077.3RefSeqNP_001020248.113Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • mRNA Processing

Biological Process

  • regulation of alternative mRNA splicing, via spliceosome
  • mRNA splice site selection
  • RNA processing
  • regulation of heart contraction

Molecular Function

  • RNA binding
  • mRNA binding
  • pre-mRNA binding

Cellular Component

  • nucleus
  • cytoplasm
  • ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000450189
Coding exons
13
Length
331416
Individuals with no LoFs
119615
Homozygous LoFs
0
Heterozygous LoFs
5
Defined
119620
p
0.0000209
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense4.34882990.2940.00001593414
Missense (PolyPhen)13107.430.121011258
Synonymous-0.4481231171.050.000006961014
Loss of Function4.66127.20.03680.00000123306

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000940.000094rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of TNNT2 in embryonic, but not adult, skeletal muscle. Activates TNNT2 exon 5 inclusion by antagonizing the repressive effect of PTB. Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre- mRNA. Involved in the apoB RNA editing activity. Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury (By similarity). Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK. Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5. Binds preferentially to UG-rich sequences, in particular UG repeat and UGUU motifs. Binds to apoB mRNA, specifically to AU-rich sequences located immediatly upstream of the edited cytidine. Binds AU-rich sequences in the 3'-UTR of COX2 mRNA (By similarity). Binds to an intronic RNA element responsible for the silencing of exon 21 splicing (By similarity). Binds to (CUG)n repeats (By similarity). May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF1, negatively regulates the processing to mature miRNA (PubMed:28431233). {ECO:0000250|UniProtKB:Q9Z0H4, ECO:0000269|PubMed:11158314, ECO:0000269|PubMed:11577082, ECO:0000269|PubMed:11931771, ECO:0000269|PubMed:12649496, ECO:0000269|PubMed:14973222, ECO:0000269|PubMed:15657417, ECO:0000269|PubMed:15894795, ECO:0000269|PubMed:28431233}.;

Recessive Scores

pRec
0.149

Intolerance Scores

RVIS EVS
-0.4
RVIS percentile EVS
26.53

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
E
Indispensability score
0.539

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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