CELF6

Summary

CELF6 (CUGBP Elav-like family member 6, HGNC:14059) is a protein-coding gene on chromosome 15q23, encoding CUGBP Elav-like family member 6 (Q96J87). RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing.

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. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene.

Source: NCBI Gene 60677 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_052840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14059
Approved symbol	CELF6
Name	CUGBP Elav-like family member 6
Location	15q23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140488
Ensembl biotype	protein_coding
OMIM	612681
Entrez	60677

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000287202, ENST00000395258, ENST00000437872, ENST00000543764, ENST00000567083, ENST00000870866, ENST00000870867, ENST00000962371, ENST00000962372

RefSeq mRNA: 3 — MANE Select: NM_052840 NM_001172684, NM_001172685, NM_052840

CCDS: CCDS10242, CCDS53955, CCDS53956

Canonical transcript exons

ENST00000287202 — 13 exons

Exon	Start	End
ENSE00001839817	72319613	72320157
ENSE00003605537	72284727	72286342
ENSE00003702550	72290127	72290255
ENSE00003702993	72288868	72288930
ENSE00003704958	72288538	72288618
ENSE00003705298	72287237	72287392
ENSE00003705774	72289939	72290018
ENSE00003706316	72288308	72288451
ENSE00003706849	72289375	72289507
ENSE00003707020	72289627	72289770
ENSE00003708034	72289138	72289287
ENSE00003708389	72315845	72315927
ENSE00003759043	72304746	72304794

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 88.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5310 / max 57.4145, expressed in 141 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150827	0.4068	129
150826	0.1241	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.95	gold quality
hypothalamus	UBERON:0001898	87.96	gold quality
pituitary gland	UBERON:0000007	87.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.13	gold quality
adenohypophysis	UBERON:0002196	85.99	gold quality
cortical plate	UBERON:0005343	85.49	gold quality
right frontal lobe	UBERON:0002810	84.62	gold quality
frontal cortex	UBERON:0001870	84.39	gold quality
frontal lobe	UBERON:0016525	84.39	gold quality
prefrontal cortex	UBERON:0000451	84.36	gold quality
superior frontal gyrus	UBERON:0002661	83.89	gold quality
sural nerve	UBERON:0015488	83.76	gold quality
anterior cingulate cortex	UBERON:0009835	83.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.70	gold quality
cerebral cortex	UBERON:0000956	82.63	gold quality
cerebellar hemisphere	UBERON:0002245	82.31	gold quality
cerebellar cortex	UBERON:0002129	82.24	gold quality
cerebellum	UBERON:0002037	82.15	gold quality
right lobe of thyroid gland	UBERON:0001119	81.92	gold quality
left ovary	UBERON:0002119	81.48	gold quality
brain	UBERON:0000955	81.41	gold quality
left lobe of thyroid gland	UBERON:0001120	80.73	gold quality
thyroid gland	UBERON:0002046	80.68	gold quality
right ovary	UBERON:0002118	80.57	gold quality
endocervix	UBERON:0000458	79.61	gold quality
nucleus accumbens	UBERON:0001882	79.56	gold quality
ovary	UBERON:0000992	79.49	gold quality
substantia nigra	UBERON:0002038	78.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting CELF6, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-361-5P	98.95	70.16	1340

Literature-anchored findings (GeneRIF, showing 7)

• CELF6 is a member of the CELF family of RNA-binding proteins that regulates muscle-specific splicing enhancer-dependent alternative splicing (PMID:14761971)
• Analysis of common variants near the corresponding genes implicated the RNA binding protein CELF6 in autism risk (PMID:23407934)
• RNA-binding protein CELF6 is cell cycle regulated and controls cancer cell proliferation by stabilizing p21. (PMID:31534127)
• CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA. (PMID:32601971)
• CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3’ UTR Elements. (PMID:33357440)
• The natural compound neobractatin inhibits cell proliferation mainly by regulating the RNA binding protein CELF6. (PMID:35088780)
• RNA-binding protein CELF6 modulates transcription and splicing levels of genes associated with tumorigenesis in lung cancer A549 cells. (PMID:35910766)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	celf6	ENSDARG00000101933
mus_musculus	Celf6	ENSMUSG00000032297
rattus_norvegicus	Celf6	ENSRNOG00000052224
drosophila_melanogaster	bru3	FBGN0264001
caenorhabditis_elegans	unc-75	WBGENE00006807

Paralogs (6): CELF2 (ENSG00000048740), CELF4 (ENSG00000101489), RBM28 (ENSG00000106344), CELF1 (ENSG00000149187), CELF3 (ENSG00000159409), CELF5 (ENSG00000161082)

Protein

Protein identifiers

CUGBP Elav-like family member 6 — Q96J87 (reviewed: Q96J87)

Alternative names: Bruno-like protein 6, CUG-BP- and ETR-3-like factor 6, RNA-binding protein BRUNOL-6

All UniProt accessions (2): Q96J87, F6UBL3

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing. 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 a muscle-specific splicing enhancer (MSE)-dependent manner. Promotes also exon exclusion of INSR pre-mRNA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed mainly in kidney, brain and testis and present in other tissues albeit at lower levels. Also expressed in fetal kidney.

Similarity. Belongs to the CELF/BRUNOL family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96J87-1	1	yes
Q96J87-2	2
Q96J87-3	3
Q96J87-4	4

RefSeq proteins (3): NP_001166155, NP_001166156, NP_443072* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034648	CELF3/4/5/6_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (24 total): splice variant 6, strand 5, domain 3, sequence conflict 2, helix 2, turn 2, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DGQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96J87-F1	69.19	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GGGACCA_MIR133A_MIR133B, TGGTGCT_MIR29A_MIR29B_MIR29C, FREAC2_01, GGTGTGT_MIR329, PAX4_01, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, FOXO4_01, CTATGCA_MIR153, PAX2_01, FREAC3_01, E4F1_Q6, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, AAAGACA_MIR511, GOBP_RNA_SPLICING, GOBP_MRNA_SPLICE_SITE_RECOGNITION

GO Biological Process (3): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splice site recognition (GO:0006376), mRNA processing (GO:0006397)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
spliceosomal complex assembly	1
protein-RNA complex assembly	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELF6	RRM2	P31350	801
CELF6	CEBPD	P49716	797
CELF6	RRM1	P23921	763
CELF6	TNNT2	P45379	607
CELF6	INSR	P06213	450
CELF6	MBNL1	Q9NR56	444
CELF6	RBFOX1	Q9NWB1	429
CELF6	MBNL2	Q5VZF2	380
CELF6	IQCF1	Q8N6M8	374
CELF6	RBM24	Q9BX46	359
CELF6	RBM38	Q9H0Z9	351
CELF6	MBNL3	Q9NUK0	348
CELF6	OTUD7A	Q8TE49	336
CELF6	NOVA2	Q9UNW9	334
CELF6	PCBP3	P57721	328

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CELF6 (Two-hybrid), BTRC (Affinity Capture-Western), CELF6 (Affinity Capture-Western), CDKN1A (Affinity Capture-RNA), CELF6 (Co-localization), CELF6 (Affinity Capture-MS)

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
SCF-betaTRCP	“down-regulates quantity by destabilization”	CELF6	ubiquitination
CELF6	“up-regulates quantity by stabilization”	CDKN1A	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2507 predictions. Top by Δscore:

Variant	Effect	Δscore
15:72288302:G:C	donor_gain	1.0000
15:72288302:GCTCA:G	donor_loss	1.0000
15:72288303:CTCA:C	donor_loss	1.0000
15:72288304:TCA:T	donor_loss	1.0000
15:72288304:TCAC:T	donor_loss	1.0000
15:72288305:CA:C	donor_loss	1.0000
15:72288306:A:AC	donor_gain	1.0000
15:72288307:C:CA	donor_loss	1.0000
15:72288307:C:CC	donor_gain	1.0000
15:72288450:GCCTG:G	acceptor_loss	1.0000
15:72288452:C:CC	acceptor_gain	1.0000
15:72289133:CCCA:C	donor_loss	1.0000
15:72289134:CCA:C	donor_loss	1.0000
15:72289135:CAC:C	donor_loss	1.0000
15:72289135:CACCT:C	donor_loss	1.0000
15:72289136:ACCTG:A	donor_loss	1.0000
15:72289137:C:CA	donor_loss	1.0000
15:72289285:CTG:C	acceptor_gain	1.0000
15:72289288:C:CC	acceptor_gain	1.0000
15:72289295:C:CT	acceptor_gain	1.0000
15:72289504:GGAT:G	acceptor_gain	1.0000
15:72289508:C:CC	acceptor_gain	1.0000
15:72289509:T:C	acceptor_gain	1.0000
15:72289510:T:C	acceptor_gain	1.0000
15:72289622:CCTA:C	donor_loss	1.0000
15:72289624:TA:T	donor_loss	1.0000
15:72289625:A:AC	donor_gain	1.0000
15:72289626:C:CA	donor_gain	1.0000
15:72289626:C:CC	donor_gain	1.0000
15:72289626:CCG:C	donor_gain	1.0000

AlphaMissense

3112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:72287295:C:A	K472N	1.000
15:72287295:C:G	K472N	1.000
15:72287297:T:C	K472E	1.000
15:72287305:A:T	V469D	1.000
15:72287307:C:A	K468N	1.000
15:72287307:C:G	K468N	1.000
15:72287309:T:C	K468E	1.000
15:72287311:A:G	L467P	1.000
15:72287311:A:T	L467H	1.000
15:72287350:A:T	I454N	1.000
15:72287353:G:T	A453D	1.000
15:72287362:G:T	A450D	1.000
15:72287380:A:G	F444S	1.000
15:72287382:A:C	S443R	1.000
15:72287382:A:T	S443R	1.000
15:72287384:T:G	S443R	1.000
15:72287386:A:T	V442D	1.000
15:72287388:A:C	F441L	1.000
15:72287388:A:T	F441L	1.000
15:72287389:A:G	F441S	1.000
15:72287390:A:G	F441L	1.000
15:72287392:C:T	G440E	1.000
15:72288308:C:A	G440W	1.000
15:72288308:C:G	G440R	1.000
15:72288308:C:T	G440R	1.000
15:72288309:A:C	F439L	1.000
15:72288309:A:T	F439L	1.000
15:72288310:A:C	F439C	1.000
15:72288310:A:G	F439S	1.000
15:72288311:A:G	F439L	1.000

dbSNP variants (sampled 300 via entrez): RS1000018610 (15:72302257 G>T), RS1000128560 (15:72309234 G>A,T), RS1000129131 (15:72286809 C>T), RS1000135030 (15:72298978 C>G), RS1000222433 (15:72290739 C>T), RS1000339134 (15:72316164 G>A), RS1000402154 (15:72298570 T>G), RS1000711792 (15:72290209 C>T), RS1000833918 (15:72310453 C>T), RS1000916845 (15:72319395 G>T), RS1001052320 (15:72303587 G>C), RS1001122813 (15:72315692 T>C), RS1001192512 (15:72289603 C>A,G,T), RS1001223284 (15:72289327 G>A,C,T), RS1001235806 (15:72315345 T>A)

Disease associations

OMIM: gene MIM:612681 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008163_482	Height	1.000000e-06
GCST90000025_221	Appendicular lean mass	1.000000e-10
GCST90011898_41	Alanine aminotransferase levels	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
fluorene-9-bisphenol	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
aflatoxin B2	decreases methylation	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Gold Compounds	increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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