CELF2

Summary

CELF2 (CUGBP Elav-like family member 2, HGNC:2550) is a protein-coding gene on chromosome 10p14, encoding CUGBP Elav-like family member 2 (O95319). RNA-binding protein implicated in the regulation of several post-transcriptional events.

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.

Source: NCBI Gene 10659 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy 97 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 32
• Clinical variants (ClinVar): 116 total — 9 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes
• MANE Select transcript: NM_001326342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2550
Approved symbol	CELF2
Name	CUGBP Elav-like family member 2
Location	10p14
Locus type	gene with protein product
Status	Approved
Aliases	Etr-3, NAPOR-2, BRUNOL3
Ensembl gene	ENSG00000048740
Ensembl biotype	protein_coding
OMIM	602538
Entrez	10659

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 2 nonsense_mediated_decay

ENST00000354897, ENST00000399850, ENST00000416382, ENST00000417956, ENST00000542579, ENST00000608830, ENST00000609692, ENST00000609870, ENST00000631460, ENST00000631816, ENST00000632065, ENST00000632728, ENST00000633077, ENST00000633200, ENST00000636488, ENST00000637215, ENST00000638035, ENST00000904654, ENST00000904655

RefSeq mRNA: 41 — MANE Select: NM_001326342 NM_001025076, NM_001025077, NM_001083591, NM_001326317, NM_001326318, NM_001326319, NM_001326320, NM_001326321, NM_001326323, NM_001326324, NM_001326325, NM_001326326, NM_001326327, NM_001326328, NM_001326329, NM_001326330, NM_001326331, NM_001326332, NM_001326333, NM_001326334, NM_001326335, NM_001326336, NM_001326337, NM_001326338, NM_001326339, NM_001326340, NM_001326341, NM_001326342, NM_001326343, NM_001326344, NM_001326345, NM_001326346, NM_001326347, NM_001326348, NM_001326349, NM_001394502, NM_001394513, NM_001394517, NM_001394518, NM_001394519, NM_006561

CCDS: CCDS41488, CCDS44354, CCDS44355, CCDS44356, CCDS86069, CCDS86070, CCDS86071, CCDS86072

Canonical transcript exons

ENST00000633077 — 13 exons

Exon	Start	End
ENSE00000915134	11217425	11217507
ENSE00001605469	11314139	11314258
ENSE00001628998	11321189	11321386
ENSE00001649912	11275057	11275120
ENSE00001667240	11288418	11288552
ENSE00001677747	11266598	11266677
ENSE00001754622	11270666	11270824
ENSE00001772482	11257738	11257872
ENSE00001779816	11249153	11249201
ENSE00001794829	11325836	11325979
ENSE00003633961	11165486	11165682
ENSE00003776970	11017872	11018163
ENSE00003777692	11328926	11336675

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.9814 / max 2360.2953, expressed in 1516 samples.

FANTOM5 promoters (39 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103865	33.4832	691
103857	13.6412	1191
103846	5.5064	985
103840	4.5271	233
103849	3.0211	824
103862	1.6712	414
103864	1.6266	359
103854	1.5323	346
103863	1.1176	279
103826	1.0700	70

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	99.28	gold quality
orbitofrontal cortex	UBERON:0004167	99.26	gold quality
entorhinal cortex	UBERON:0002728	99.20	gold quality
trabecular bone tissue	UBERON:0002483	99.17	gold quality
middle temporal gyrus	UBERON:0002771	99.12	gold quality
postcentral gyrus	UBERON:0002581	99.11	gold quality
parietal lobe	UBERON:0001872	99.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.83	gold quality
cortical plate	UBERON:0005343	98.70	gold quality
germinal epithelium of ovary	UBERON:0001304	98.60	gold quality
heart right ventricle	UBERON:0002080	98.57	gold quality
superficial temporal artery	UBERON:0001614	98.42	gold quality
skin of hip	UBERON:0001554	98.41	gold quality
adult organism	UBERON:0007023	98.33	gold quality
synovial joint	UBERON:0002217	98.32	gold quality
lower lobe of lung	UBERON:0008949	98.32	gold quality
superior frontal gyrus	UBERON:0002661	98.31	gold quality
endothelial cell	CL:0000115	98.30	gold quality
olfactory bulb	UBERON:0002264	98.19	gold quality
nipple	UBERON:0002030	98.10	gold quality
pigmented layer of retina	UBERON:0001782	98.09	gold quality
parietal pleura	UBERON:0002400	97.97	gold quality
trigeminal ganglion	UBERON:0001675	97.84	gold quality
blood	UBERON:0000178	97.73	gold quality
pleura	UBERON:0000977	97.48	gold quality
visceral pleura	UBERON:0002401	97.47	gold quality
secondary oocyte	CL:0000655	97.44	gold quality
ventral tegmental area	UBERON:0002691	97.28	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	5509.93
E-CURD-119	yes	5019.96
E-HCAD-35	yes	2711.32
E-HCAD-25	yes	2483.89
E-HCAD-5	yes	48.78
E-CURD-46	yes	38.06
E-MTAB-10287	yes	29.59
E-CURD-122	yes	21.56
E-ANND-3	yes	19.91
E-HCAD-10	yes	9.42
E-HCAD-30	no	2966.78
E-MTAB-6075	no	819.00
E-HCAD-6	no	29.19
E-MTAB-5061	no	3.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRX1

miRNA regulators (miRDB)

233 targeting CELF2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784

Literature-anchored findings (GeneRIF, showing 37)

• BRUNOL3 appears to be an important factor for thymus development and is therefore a candidate gene for the thymus hypoplasia/aplasia seen in partial monosomy 10p patients. (PMID:12110949)
• Determination of ETR-3 protein domains required for RNA splicing. (PMID:14973222)
• data suggest that CUGBP2 is a critical regulator of the apoptotic response to genotoxic injury in breast cancer cells (PMID:15033780)
• Developmental upregulation of apoB mRNA editing from approximately 3% to 88% begins with decreased levels of inhibitory CUG binding protein 2 (CUGBP2) expression. (PMID:16920700)
• CUGBP2 overrides HuR and suppresses COX-2 mRNA translation. (PMID:17383427)
• Data demonstrate that cells expressing CUGBP2 variant 1 undergo apoptosis during mitosis, suggesting mitotic catastrophe. (PMID:18258790)
• Demonstrate that CUGBP2 inhibits Mcl-1 expression by inhibiting Mcl-1 mRNA translation, resulting in driving the cells to apoptosis during the G(2) phase of the cell cycle. (PMID:18292181)
• There was evidence of association for recently-reported late-onset Alzheimer’s disease risk loci, including BIN1 and CLU and CUGBP2 with APOE. (PMID:21379329)
• results indicate the occurrence of a mis-splicing event in myotonic dystrophy type 1 that is induced neither by a loss of muscleblind-like 1 (MBNL1) function nor by a gain of CUGBP1 (PMID:21439371)
• Alternative splicing of LEF1 exon 6 is regulated during pre-TCR signaling in thymic development and in response to activation of the JSL1 T-cell line and this is driven by the activity of CELF2. (PMID:21444716)
• The A allele of rs2242451 in CUGBP2 might decrease Alzheimer disease risk in the Chinese Han population. (PMID:25801238)
• novel mechanisms for CELF2 regulation that may broadly impact CELF2 expression across diverse cell types. (PMID:25870297)
• Data show miR95 expression level positively related to glioma grade and its downregulation affects proliferation, invasion and apoptosis by targeting CELF2. MiR95 is identified as a putative therapeutic target and CELF2 as a potential tumor suppressor. (PMID:26165303)
• the genetic variant rs3740194 in CELF2 gene might be a valuable predictor for NPC prognosis (PMID:26314850)
• a widespread role for the JNK-CELF2 axis in controlling splicing during T-cell activation, including a specific role in propagating JNK signaling. (PMID:26443849)
• CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower and could be associated with high chemoresistance and early dissemination of pancreatic cancer. (PMID:26691217)
• Study provides evidence for a generalized position- dependent activity of CELF2 in splicing that can be used to predict its consequence on alternative splicing in a cell-type independent manner. (PMID:27096301)
• Haplotype-dependent allele-specific methylation of CELF2 gene is associated with neurological disorders. (PMID:27153397)
• These data suggest an interplay between CELF2 and hnRNP C as the mechanistic basis for activation-dependent alternative splicing of TRAF3 exon 8. (PMID:28031331)
• CUG-BP2 binds to AU-rich motifs found in the COX-2 mRNA 3’-UTR. (PMID:28935965)
• Overexpression of CELF2 could reverse miR-615-3p’s oncogenic functions. (PMID:29501762)
• These studies elucidate an unrecognized role for CELF2 in inducing autophagy and potentiating the effects of radiotherapy in colorectal cancer. (PMID:31020708)
• CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction. (PMID:31241130)
• CELF2 hypermethylation is associated with breast cancer. (PMID:31409895)
• RNA Binding Protein CELF2 Regulates Signal-Induced Alternative Polyadenylation by Competing with Enhancers of the Polyadenylation Machinery. (PMID:31509743)
• STYXL1 promotes malignant progression of hepatocellular carcinoma via downregulating CELF2 through the PI3K/Akt pathway. (PMID:32271415)
• De novo variants in CELF2 that disrupt the nuclear localization signal cause developmental and epileptic encephalopathy. (PMID:33131106)
• LncRNA-SNHG16 promotes proliferation and migration of acute myeloid leukemia cells via PTEN/PI3K/AKT axis through suppressing CELF2 protein. (PMID:33576342)
• Genome-wide association analysis of cognitive function in Danish long-lived individuals. (PMID:33607172)
• LncRNA RHPN1-AS1 promotes the progression of nasopharyngeal carcinoma by targeting CELF2 expression. (PMID:34358519)
• miR-363-3p induces EMT via the Wnt/beta-catenin pathway in glioma cells by targeting CELF2. (PMID:34636136)
• MiR-210-3p targets CELF2 to facilitate progression of lung squamous carcinoma through PI3K/AKT pathway. (PMID:35972577)
• CircLIFR Inhibits Non-small Cell Lung Cancer Progression by Acting as a miR-429 Sponge to Enhance CELF2 Expression. (PMID:36104590)
• Natural Antisense Long Noncoding RNA HHIP-AS1 Suppresses Non-Small-Cell Lung Cancer Progression by Increasing HHIP Stability via Interaction with CELF2. (PMID:36374812)
• Hypoxia-induced lncRNA MRVI1-AS1 accelerates hepatocellular carcinoma progression by recruiting RNA-binding protein CELF2 to stabilize SKA1 mRNA. (PMID:36973749)
• Role of CELF2 in ferroptosis: Potential targets for cancer therapy (Review). (PMID:37594127)
• miR-208a-3p regulated by circUQCRC2 suppresses ischemia/reperfusion-induced acute kidney injury by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis. (PMID:38664873)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	celf2	ENSDARG00000002131
danio_rerio		ENSDARG00000114049
mus_musculus	Celf2	ENSMUSG00000002107
rattus_norvegicus	Celf2	ENSRNOG00000023661
drosophila_melanogaster	bru1	FBGN0000114
drosophila_melanogaster	Pof	FBGN0035047
drosophila_melanogaster	bru2	FBGN0262475
caenorhabditis_elegans		WBGENE00017135
caenorhabditis_elegans		WBGENE00017140
caenorhabditis_elegans		WBGENE00020354

Paralogs (6): CELF4 (ENSG00000101489), RBM28 (ENSG00000106344), CELF6 (ENSG00000140488), CELF1 (ENSG00000149187), CELF3 (ENSG00000159409), CELF5 (ENSG00000161082)

Protein

Protein identifiers

CUGBP Elav-like family member 2 — O95319 (reviewed: O95319)

Alternative names: Bruno-like protein 3, CUG triplet repeat RNA-binding protein 2, CUG-BP- and ETR-3-like factor 2, ELAV-type RNA-binding protein 3, Neuroblastoma apoptosis-related RNA-binding protein, RNA-binding protein BRUNOL-3

All UniProt accessions (10): A0A0J9YX66, A0A0J9YXJ0, A0A0J9YXK1, A0A1B0GU44, A0A1B0GUN8, O95319, E9PC62, Q5VZZ6, V9GY47, V9GYD9

UniProt curated annotations — full annotation on UniProt →

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 both as an activator and as a 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. Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression. 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 immediately upstream of the edited cytidine. Binds AU-rich sequences in the 3’-UTR of COX2 mRNA. Binds to an intronic RNA element responsible for the silencing of exon 21 splicing. Binds to (CUG)n repeats. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF1, negatively regulates the processing to mature miRNA.

Subunit / interactions. Interacts with A1CF.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in frontal cortex. Isoform 1 is expressed in brain and lung. Isoform 2 is expressed in heart, brain, placenta, lung, liver, kidney, skeletal muscle and pancreas. Isoform 4 is expressed in heart, lung, skeletal muscle, kidney and pancreas.

Disease relevance. Developmental and epileptic encephalopathy 97 (DEE97) [MIM:619561] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE97 is an autosomal dominant form. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CELF/BRUNOL family.

Isoforms (5)

UniProt ID	Names	Canonical?
O95319-1	1, NAPOR-3	yes
O95319-2	2, NAPOR-1
O95319-3	3
O95319-4	4, NAPOR-2
O95319-5	5

RefSeq proteins (41): NP_001020247, NP_001020248, NP_001077060, NP_001313246, NP_001313247, NP_001313248, NP_001313249, NP_001313250, NP_001313252, NP_001313253, NP_001313254, NP_001313255, NP_001313256, NP_001313257, NP_001313258, NP_001313259, NP_001313260, NP_001313261, NP_001313262, NP_001313263, NP_001313264, NP_001313265, NP_001313266, NP_001313267, NP_001313268, NP_001313269, NP_001313270, NP_001313271, NP_001313272, NP_001313273, NP_001313274, NP_001313275, NP_001313276, NP_001313277, NP_001313278, NP_001381431, NP_001381442, NP_001381446, NP_001381447, NP_001381448, NP_006552 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002343	Hud_Sxl_RNA	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034196	CELF1/2_RRM1	Domain
IPR034198	CELF1/2_RRM2	Domain
IPR034199	CELF1/2_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (42 total): strand 15, helix 11, splice variant 5, domain 3, sequence variant 3, turn 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9URH	X-RAY DIFFRACTION	1.82
4TLQ	X-RAY DIFFRACTION	2.5
4LMZ	X-RAY DIFFRACTION	2.78
4LJM	X-RAY DIFFRACTION	3
2MY7	SOLUTION NMR
2MY8	SOLUTION NMR
5M8I	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95319-F1	66.26	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 503 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, YAATNRNNNYNATT_UNKNOWN, TAATAAT_MIR126, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_255, TGCACTT_MIR519C_MIR519B_MIR519A, PEREZ_TP63_TARGETS, TTTGTAG_MIR520D, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MODULE_45, KENNY_CTNNB1_TARGETS_UP, MODULE_317, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MODULE_16

GO Biological Process (6): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splice site recognition (GO:0006376), RNA processing (GO:0006396), regulation of heart contraction (GO:0008016), mRNA processing (GO:0006397), mRNA metabolic process (GO:0016071)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), pre-mRNA binding (GO:0036002), nucleic acid binding (GO:0003676), lncRNA binding (GO:0106222)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Flemming body (GO:0090543), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA binding	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
spliceosomal complex assembly	1
protein-RNA complex assembly	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
heart contraction	1
regulation of blood circulation	1
RNA processing	1
mRNA metabolic process	1
RNA metabolic process	1
nucleic acid binding	1
mRNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
midbody	1
protein-containing complex	1

Protein interactions and networks

STRING

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELF2	CEBPD	P49716	893
CELF2	TNNT2	P45379	849
CELF2	MBNL1	Q9NR56	735
CELF2	PTGS2	P35354	713
CELF2	PTBP2	Q9UKA9	698
CELF2	DMPK	Q09013	662
CELF2	PTBP1	P26599	651
CELF2	MBNL2	Q5VZF2	646
CELF2	CHCHD7	Q9BUK0	631
CELF2	HNRNPC	P07910	616
CELF2	MBNL3	Q9NUK0	609
CELF2	SRSF2	Q01130	608
CELF2	RBFOX2	O43251	600
CELF2	MCL1	Q07820	595
CELF2	HNRNPM	P52272	541

IntAct

16 interactions, top by confidence:

A	B	Type	Score
CELF2	GRB2	psi-mi:“MI:0915”(physical association)	0.400
	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
	DDX3X	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
	RTCA	psi-mi:“MI:0914”(association)	0.350
	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
FN1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350
NONO	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
CELF1	CELF2	psi-mi:“MI:0915”(physical association)	0.000
CELF2	ribF	psi-mi:“MI:0915”(physical association)	0.000
PCBP1	CELF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): CELF2 (Reconstituted Complex), CELF2 (Affinity Capture-MS), CELF2 (Affinity Capture-MS), CELF2 (Affinity Capture-MS), TRAF3 (Protein-RNA), CELF2 (Affinity Capture-MS), CELF2 (Affinity Capture-MS), CELF2 (Protein-RNA), CELF2 (Protein-RNA), CELF2 (Protein-RNA), CELF2 (Protein-RNA), CELF2 (Protein-RNA), CELF2 (Protein-RNA), CELF2 (Protein-RNA), CELF2 (Protein-RNA)

ESM2 similar proteins: A0A1W2P872, A1L1C7, A4IIM2, B2RYD2, F1LQ48, O57406, O88532, O95319, P14866, P28659, P51513, P57723, P57724, Q28HE9, Q2PFW9, Q32PX7, Q3U0V1, Q3US41, Q4QQT3, Q4R535, Q58A45, Q5F3T7, Q5NVC8, Q5R8Y8, Q5R995, Q5U231, Q640Q5, Q6DGV1, Q6GPM1, Q6NXG1, Q6P0B1, Q6PF35, Q792H5, Q7T2T1, Q7TSY6, Q7ZXE2, Q80WA4, Q8R081, Q8UVD9, Q91WJ8

Diamond homologs: A0A0D1DWZ5, A0JM51, A1CRM1, A1D4K4, A2A5N3, A2Q848, A3LXL0, A4IIM2, A4QUF0, A5DW14, F4HT49, O04319, O14102, O22173, O57406, O64380, O95319, O97018, P04147, P0CB38, P0CP46, P0CP47, P20965, P21187, P28659, P29558, P31209, P32588, P39697, P42731, P60047, P60048, P60049, P60050, Q08E07, Q09442, Q0CR95, Q0U1G2, Q13310, Q15427

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IRX1	“down-regulates quantity by repression”	CELF2	“transcriptional regulation”
SRC	“up-regulates activity”	CELF2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

116 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	5
Uncertain significance	69
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1299463	NM_001326342.2(CELF2):c.1558C>T (p.Pro520Ser)	Pathogenic
1299464	NM_001326342.2(CELF2):c.1516C>G (p.Arg506Gly)	Pathogenic
1299465	NM_001326342.2(CELF2):c.1562dup (p.Tyr521Ter)	Pathogenic
1334733	NM_001326342.2(CELF2):c.1517G>A (p.Arg506His)	Pathogenic
1398077	NM_001326342.2(CELF2):c.1563C>G (p.Tyr521Ter)	Pathogenic
1685612	NM_001326342.2(CELF2):c.1353del (p.Asp451fs)	Pathogenic
2579922	NM_001326342.2(CELF2):c.1517G>T (p.Arg506Leu)	Pathogenic
3359034	NM_001326342.2(CELF2):c.883del (p.Ala295fs)	Pathogenic
3391850	GRCh37/hg19 10p15.3-12.31(chr10:100027-18976780)x3	Pathogenic
3054657	NM_001326342.2(CELF2):c.977-2A>T	Likely pathogenic
3338598	NM_001326342.2(CELF2):c.938_939del (p.Ser313fs)	Likely pathogenic
3375484	NM_001326342.2(CELF2):c.241_262dup (p.Gln88fs)	Likely pathogenic
4526633	NM_001326342.2(CELF2):c.1412_1415del (p.Lys471fs)	Likely pathogenic
4539930	NM_001326342.2(CELF2):c.1538G>A (p.Arg513His)	Likely pathogenic

SpliceAI

4385 predictions. Top by Δscore:

Variant	Effect	Δscore
10:11054700:G:T	donor_gain	1.0000
10:11155539:G:T	donor_gain	1.0000
10:11165480:T:A	acceptor_gain	1.0000
10:11165484:A:AG	acceptor_gain	1.0000
10:11165485:G:GC	acceptor_gain	1.0000
10:11165485:GT:G	acceptor_gain	1.0000
10:11165485:GTA:G	acceptor_gain	1.0000
10:11165485:GTAAC:G	acceptor_gain	1.0000
10:11165680:AAGG:A	donor_loss	1.0000
10:11165681:AG:A	donor_loss	1.0000
10:11165683:GTACA:G	donor_loss	1.0000
10:11257736:A:AG	acceptor_gain	1.0000
10:11257737:G:GA	acceptor_gain	1.0000
10:11257737:GCT:G	acceptor_gain	1.0000
10:11257870:GAG:G	donor_gain	1.0000
10:11257873:G:GC	donor_loss	1.0000
10:11257873:G:GG	donor_gain	1.0000
10:11257874:T:G	donor_loss	1.0000
10:11270823:CGGTA:C	donor_loss	1.0000
10:11270825:G:GA	donor_loss	1.0000
10:11270826:T:TC	donor_loss	1.0000
10:11288415:CAGG:C	acceptor_loss	1.0000
10:11288416:A:AG	acceptor_gain	1.0000
10:11288416:AG:A	acceptor_gain	1.0000
10:11288417:G:GG	acceptor_gain	1.0000
10:11288417:GG:G	acceptor_gain	1.0000
10:11288417:GGC:G	acceptor_gain	1.0000
10:11288417:GGCA:G	acceptor_gain	1.0000
10:11288417:GGCAT:G	acceptor_gain	1.0000
10:11288551:CGGT:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006573 (10:10904461 G>A), RS1000008989 (10:11083663 C>T), RS1000009286 (10:11230463 A>C), RS1000009402 (10:10840848 C>A,G), RS1000018428 (10:10717957 T>C), RS1000018471 (10:10926625 C>T), RS1000018916 (10:10723904 T>A,C), RS1000023619 (10:11160011 A>G), RS1000025145 (10:10624492 A>C,G,T), RS1000026352 (10:11195028 G>A), RS1000026738 (10:10715394 A>G), RS1000029875 (10:11122162 G>A,C,T), RS1000029926 (10:10823222 T>C), RS1000030629 (10:10764951 A>C,T), RS1000034984 (10:10520077 A>G)

Disease associations

OMIM: gene MIM:602538 | disease phenotypes: MIM:619561, MIM:614959

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy 97	Strong	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (5): developmental and epileptic encephalopathy 97 (MONDO:0030453), neurodevelopmental disorder (MONDO:0700092), developmental and epileptic encephalopathy, 14 (MONDO:0013989), complex neurodevelopmental disorder (MONDO:0100038), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (1): Epilepsy of infancy with migrating focal seizures (Orphanet:293181)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001508	Failure to thrive

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000980_1	Alzheimer’s disease (late onset)	2.000000e-07
GCST001762_339	Obesity-related traits	4.000000e-06
GCST002207_3	Liver enzyme levels (alanine transaminase)	9.000000e-06
GCST002208_2	Liver enzyme levels (aspartate transaminase)	4.000000e-07
GCST002715_8	Breastfeeding duration	9.000000e-06
GCST002759_21	Motion sickness	1.000000e-10
GCST003255_10	Urinary albumin-to-creatinine ratio	2.000000e-06
GCST004839_1	Colorectal cancer	9.000000e-08
GCST005212_13	Asthma	4.000000e-09
GCST006409_21	Allergic rhinitis	3.000000e-12
GCST006629_75	Pulse pressure	1.000000e-12
GCST006862_7	Asthma	2.000000e-10
GCST007324_1	Adventurousness	7.000000e-10
GCST007325_104	General risk tolerance (MTAG)	2.000000e-10
GCST007879_2	Chronic kidney disease	3.000000e-08
GCST007993_8	Asthma (adult onset)	5.000000e-29
GCST007995_30	Asthma (childhood onset)	9.000000e-11
GCST007995_31	Asthma (childhood onset)	3.000000e-13
GCST008363_117	Offspring birth weight	3.000000e-08
GCST008674_13	Glycemic traits (pleiotropy)	3.000000e-11
GCST008719_1	Follicular lymphoma or rheumatoid arthritis	3.000000e-08
GCST009028_55	Adverse response to drug	2.000000e-07
GCST010294_3	Response to lamotrigine in genetic generalized epilepsy	6.000000e-06
GCST010988_436	Adult body size	2.000000e-08
GCST010989_83	Body size at age 10	1.000000e-08
GCST012040_1	Activity variability during wake	3.000000e-08
GCST012170_7	Cognitive function in longevity	4.000000e-06
GCST90000047_206	Age at first sexual intercourse	5.000000e-11
GCST90002395_69	Mean platelet volume	7.000000e-12
GCST90011770_23	Glaucoma (primary open-angle)	7.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0006864	breastfeeding duration
EFO:0006928	motion sickness
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:1002011	adult onset asthma
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004469	HOMA-B
EFO:0009658	adverse effect
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008002	physical activity measurement
EFO:0008354	cognitive function measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066989 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.34	Kd	0.046	nM	CHEMBL5653589
9.68	ED50	0.21	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148059: Binding affinity to human CELF2 incubated for 45 mins by Kinobead based pull down assay	kd	<0.0001	uM

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, increases mutagenesis, affects methylation	5
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	5
bisphenol A	increases methylation, increases expression, affects methylation, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	affects methylation, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
Cisplatin	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	increases methylation	1
methylmercuric chloride	decreases expression	1
cobaltous chloride	decreases expression	1
Huang Qi	decreases reaction, increases expression, affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Coptidis rhizoma extract	affects cotreatment, decreases expression, decreases reaction, increases expression	1
2-palmitoylglycerol	increases expression	1
2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Centella asiatica extract	affects cotreatment, decreases expression, decreases reaction, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sugars	affects cotreatment, decreases expression, decreases reaction, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aconitic Acid	decreases expression, decreases reaction, increases expression, affects cotreatment	1
Colchicine	increases expression, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651101	Binding	Binding affinity to human CELF2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D0P0	UOCi003-A	Induced pluripotent stem cell	Female
CVCL_D0P5	UOCi003-A-1	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

204 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism