CELF5

Summary

CELF5 (CUGBP Elav-like family member 5, HGNC:14058) is a protein-coding gene on chromosome 19p13.3, encoding CUGBP Elav-like family member 5 (Q8N6W0). RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing.

This gene encodes a member of the the CELF/BRUNOL protein family, which 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. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 60680 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_021938

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14058
Approved symbol	CELF5
Name	CUGBP Elav-like family member 5
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000161082
Ensembl biotype	protein_coding
OMIM	612680
Entrez	60680

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000292672, ENST00000334293, ENST00000541430, ENST00000586050, ENST00000588101, ENST00000588350, ENST00000589370, ENST00000591483, ENST00000872552, ENST00000935823

RefSeq mRNA: 2 — MANE Select: NM_021938 NM_001172673, NM_021938

CCDS: CCDS12106, CCDS54197

Canonical transcript exons

ENST00000292672 — 13 exons

Exon	Start	End
ENSE00000859555	3224661	3224998
ENSE00001056280	3290231	3290374
ENSE00001357967	3296758	3297076
ENSE00003495096	3284902	3284964
ENSE00003497398	3282126	3282267
ENSE00003502035	3250985	3251067
ENSE00003508815	3285942	3286025
ENSE00003524686	3278031	3278110
ENSE00003574832	3282352	3282498
ENSE00003598638	3275856	3275984
ENSE00003602517	3293319	3293486
ENSE00003630144	3281199	3281345
ENSE00003758921	3273872	3273923

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.57.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2206 / max 191.0573, expressed in 241 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173163	1.0999	105
173160	0.8390	134
173159	0.6390	189
173161	0.3224	92
173166	0.1659	66
173162	0.1545	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.57	gold quality
middle temporal gyrus	UBERON:0002771	98.71	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.40	gold quality
cortical plate	UBERON:0005343	97.80	gold quality
superior frontal gyrus	UBERON:0002661	96.90	gold quality
buccal mucosa cell	CL:0002336	96.66	gold quality
entorhinal cortex	UBERON:0002728	96.63	gold quality
nucleus accumbens	UBERON:0001882	96.02	gold quality
primary visual cortex	UBERON:0002436	95.77	gold quality
temporal lobe	UBERON:0001871	95.33	gold quality
postcentral gyrus	UBERON:0002581	95.26	gold quality
right frontal lobe	UBERON:0002810	95.14	gold quality
parietal lobe	UBERON:0001872	95.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.94	gold quality
anterior cingulate cortex	UBERON:0009835	94.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.63	gold quality
amygdala	UBERON:0001876	94.53	gold quality
cerebral cortex	UBERON:0000956	94.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.49	gold quality
neocortex	UBERON:0001950	94.35	gold quality
cerebellar hemisphere	UBERON:0002245	94.33	gold quality
cerebellar cortex	UBERON:0002129	94.31	gold quality
frontal cortex	UBERON:0001870	94.30	gold quality
ganglionic eminence	UBERON:0004023	94.30	gold quality
cerebellar vermis	UBERON:0004720	94.13	gold quality
cerebellum	UBERON:0002037	94.11	gold quality
occipital lobe	UBERON:0002021	94.07	gold quality
putamen	UBERON:0001874	93.96	gold quality
caudate nucleus	UBERON:0001873	93.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	12.81
E-GEOD-93593	yes	11.84
E-ANND-3	yes	2.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting CELF5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-208A-3P	95.87	66.51	397
HSA-MIR-208B-3P	95.87	66.56	396

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	celf5a	ENSDARG00000071375
danio_rerio	celf5b	ENSDARG00000090727
mus_musculus	Celf5	ENSMUSG00000034818
rattus_norvegicus	Celf5	ENSRNOG00000004695
drosophila_melanogaster	bru3	FBGN0264001
caenorhabditis_elegans	unc-75	WBGENE00006807

Paralogs (6): CELF2 (ENSG00000048740), CELF4 (ENSG00000101489), RBM28 (ENSG00000106344), CELF6 (ENSG00000140488), CELF1 (ENSG00000149187), CELF3 (ENSG00000159409)

Protein

Protein identifiers

CUGBP Elav-like family member 5 — Q8N6W0 (reviewed: Q8N6W0)

Alternative names: Bruno-like protein 5, CUG-BP- and ETR-3-like factor 5, RNA-binding protein BRUNOL-5

All UniProt accessions (3): Q8N6W0, B4DFI3, K7ES14

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 cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in brain.

Similarity. Belongs to the CELF/BRUNOL family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N6W0-1	1	yes
Q8N6W0-2	2

RefSeq proteins (2): NP_001166144, NP_068757* (*=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 (20 total): strand 5, domain 3, splice variant 3, helix 2, compositionally biased region 2, chain 1, sequence variant 1, sequence conflict 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DNH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6W0-F1	68.74	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_MRNA_SPLICE_SITE_RECOGNITION, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_REGULATION_OF_RNA_SPLICING, GOCC_RIBONUCLEOPROTEIN_COMPLEX, chr19p13, GOMF_MRNA_BINDING, GSE13522_WT_VS_IFNG_KO_SKIN_DN, GOMF_PRE_MRNA_BINDING, GOBP_REGULATION_OF_MRNA_PROCESSING, GOBP_MRNA_PROCESSING, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNG_KO_DN

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 (5): mRNA binding (GO:0003729), pre-mRNA binding (GO:0036002), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), 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
RNA binding	2
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
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

780 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELF5	CEBPD	P49716	831
CELF5	TNNT2	P45379	676
CELF5	MBNL2	Q5VZF2	535
CELF5	MBNL3	Q9NUK0	528
CELF5	CLCN1	P35523	511
CELF5	MBNL1	Q9NR56	445
CELF5	PSIP1	O75475	412
CELF5	USP49	Q70CQ1	395
CELF5	ZCCHC24	Q8N2G6	372
CELF5	C5orf47	Q569G3	371
CELF5	RBM11	P57052	370
CELF5	ESRP2	Q9H6T0	360
CELF5	ABLIM1	O14639	353
CELF5	PLEKHB2	Q96CS7	348
CELF5	HNRNPH2	P55795	346

IntAct

77 interactions, top by confidence:

A	B	Type	Score
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
DAZAP2	CELF5	psi-mi:“MI:0915”(physical association)	0.600
CELF5		psi-mi:“MI:0915”(physical association)	0.560
CELF5	VASN	psi-mi:“MI:0915”(physical association)	0.560
	CELF5	psi-mi:“MI:0915”(physical association)	0.560
VASN	CELF5	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CELF5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	CELF5	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	CELF5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	CELF5	psi-mi:“MI:0915”(physical association)	0.560
CELF5	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
CELF5	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	CELF5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	CELF5	psi-mi:“MI:0915”(physical association)	0.560
CELF5	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.560
CELF5	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
CELF5	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-1	CELF5	psi-mi:“MI:0915”(physical association)	0.560
CELF5	PRR13	psi-mi:“MI:0915”(physical association)	0.560
RBM47	CELF5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP26-1	CELF5	psi-mi:“MI:0915”(physical association)	0.560
CELF5	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP7-1	CELF5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-5	CELF5	psi-mi:“MI:0915”(physical association)	0.560
CELF5	CASC3	psi-mi:“MI:0914”(association)	0.530
CELF3	CELF5	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): CELF5 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), SMAP2 (Affinity Capture-MS), PAIP2B (Affinity Capture-MS), TNKS (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), IARS2 (Affinity Capture-MS), PAIP1 (Affinity Capture-MS), ELAVL2 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), RBM47 (Two-hybrid), DAZAP2 (Two-hybrid)

ESM2 similar proteins: A0A0R4IEW8, A0JM51, A4QNI8, O09032, O57406, P26378, P29558, Q08E07, Q0V9L3, Q14576, Q15434, Q1RMJ7, Q28GD4, Q3ZBP3, Q3ZC34, Q4R535, Q5NVC8, Q5PQP1, Q5R995, Q5RBD3, Q5SZQ8, Q60899, Q60900, Q61701, Q62176, Q6DGV1, Q6DIV4, Q6XE24, Q6YZW2, Q7SZT7, Q7T3I7, Q7TN33, Q7TSY6, Q7ZWM3, Q8BWL5, Q8CH84, Q8CIN6, Q8N6W0, Q8VC70, Q8VXZ9

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	13	36.2×	3e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2971 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3250979:TTCCA:T	acceptor_loss	1.0000
19:3250980:TCCA:T	acceptor_loss	1.0000
19:3250981:CCA:C	acceptor_loss	1.0000
19:3250982:CAGGC:C	acceptor_loss	1.0000
19:3250983:A:AG	acceptor_gain	1.0000
19:3250983:A:T	acceptor_loss	1.0000
19:3250984:G:GA	acceptor_loss	1.0000
19:3250984:G:GG	acceptor_gain	1.0000
19:3251065:GGA:G	donor_gain	1.0000
19:3251066:GA:G	donor_gain	1.0000
19:3251066:GAG:G	donor_gain	1.0000
19:3251068:G:GG	donor_gain	1.0000
19:3273918:G:GT	donor_gain	1.0000
19:3273982:A:T	donor_gain	1.0000
19:3278023:T:TA	acceptor_gain	1.0000
19:3278111:G:GG	donor_gain	1.0000
19:3281343:GCT:G	donor_gain	1.0000
19:3281346:G:GG	donor_gain	1.0000
19:3282264:TCTGG:T	donor_loss	1.0000
19:3282265:CTGGT:C	donor_loss	1.0000
19:3282268:GT:G	donor_loss	1.0000
19:3282269:T:A	donor_loss	1.0000
19:3284900:A:AG	acceptor_gain	1.0000
19:3284901:G:GG	acceptor_gain	1.0000
19:3284901:GCTCA:G	acceptor_gain	1.0000
19:3284961:ACAGG:A	donor_loss	1.0000
19:3284962:CAGG:C	donor_loss	1.0000
19:3284963:AGGTA:A	donor_loss	1.0000
19:3284964:GGTA:G	donor_loss	1.0000
19:3284965:G:GA	donor_loss	1.0000

AlphaMissense

3166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3224879:T:C	L47P	1.000
19:3224881:T:C	F48L	1.000
19:3224882:T:C	F48S	1.000
19:3224882:T:G	F48C	1.000
19:3224883:C:A	F48L	1.000
19:3224883:C:G	F48L	1.000
19:3224888:G:A	G50D	1.000
19:3224921:T:C	L61P	1.000
19:3224960:T:C	L74P	1.000
19:3250991:C:A	A89D	1.000
19:3250993:T:C	F90L	1.000
19:3250994:T:C	F90S	1.000
19:3250994:T:G	F90C	1.000
19:3250995:C:A	F90L	1.000
19:3250995:C:G	F90L	1.000
19:3250997:T:A	L91H	1.000
19:3250997:T:C	L91P	1.000
19:3251002:T:G	Y93D	1.000
19:3251021:C:A	A99D	1.000
19:3275868:T:A	L136Q	1.000
19:3275868:T:C	L136P	1.000
19:3275870:T:A	F137I	1.000
19:3275870:T:C	F137L	1.000
19:3275870:T:G	F137V	1.000
19:3275871:T:C	F137S	1.000
19:3275871:T:G	F137C	1.000
19:3275872:C:A	F137L	1.000
19:3275872:C:G	F137L	1.000
19:3275874:T:A	V138E	1.000
19:3275876:G:A	G139R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000015 (19:3228462 G>A), RS1000005155 (19:3289412 T>C), RS1000006588 (19:3258293 T>G), RS1000030484 (19:3295696 CCA>C), RS1000137241 (19:3241175 C>T), RS1000139516 (19:3295322 C>T), RS1000180060 (19:3273423 A>C), RS1000224413 (19:3234206 A>G), RS1000232265 (19:3273157 C>T), RS1000241431 (19:3280399 C>T), RS1000281193 (19:3268596 G>A,C), RS1000350315 (19:3274220 A>C), RS1000374978 (19:3231500 G>A), RS1000411755 (19:3268440 C>G), RS1000638926 (19:3245328 G>C)

Disease associations

OMIM: gene MIM:612680 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005974_21	Neutrophil count	9.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
trichostatin A	affects cotreatment, decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
fluorene-9-bisphenol	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation, increases methylation, affects cotreatment	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
butylparaben	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases mutagenesis	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Endosulfan	increases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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