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
• GTEx eGene: eQTL in 21 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.08 (unconstrained)
• MANE Select transcript: NM_052840
• Notable: 70 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 14 — 9 protein_coding, 5 nonsense_mediated_decay

MANE Select: ENST00000287202

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 5: 1

ENST00000287202, ENST00000395258, ENST00000437872, ENST00000543764, ENST00000567083, ENST00000870866, ENST00000870867, ENST00000962371, ENST00000962372, ENST00001050430, ENST00001050431, ENST00001050432, ENST00001124492, ENST00001132593

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.

Highest expression (Bgee): uterine tube, hypothalamus, pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CELF6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Muscularis	eqtl	4.2e-07	-0.47	15:72345454:T:C
Artery Tibial	eqtl	2.2e-05	-0.34	15:72354272:A:G
Brain Cerebellum	eqtl	3.6e-05	+1.25	15:71767123:C:A
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-04	-0.52	15:72396580:A:G
Artery Aorta	eqtl	5.3e-04	-0.33	15:72336539:T:C
Brain Putamen basal ganglia	eqtl	6.1e-04	-0.65	15:72366858:T:A
Thyroid	eqtl	7.4e-04	-0.35	15:72375175:A:G
Esophagus Gastroesophageal Junction	eqtl	1.3e-03	-0.41	15:72363553:G:A
Muscle Skeletal	eqtl	1.4e-03	-0.32	15:72354272:A:G
Testis	sqtl	1.6e-03	+1.37	15:72294238:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-03	-0.34	15:72336539:T:C
Adipose Visceral Omentum	eqtl	2.1e-03	-0.33	15:72375175:A:G
Whole Blood	eqtl	3.6e-03	-0.30	15:72345454:T:C
Cells Cultured fibroblasts	eqtl	7.0e-03	-0.15	15:72338763:A:AG
Skin Sun Exposed Lower leg	eqtl	1.3e-02	-0.29	15:72339708:G:A
Brain Cerebellar Hemisphere	eqtl	1.5e-02	-0.52	15:72422623:G:A
Esophagus Mucosa	eqtl	1.9e-02	+0.58	15:72345367:T:C
Colon Sigmoid	eqtl	2.6e-02	+0.42	15:72298247:C:T
Colon Transverse	eqtl	2.7e-02	-0.23	15:72337380:T:C
Pancreas	eqtl	2.8e-02	+0.31	15:71364384:G:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 138 tissues 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
right testis	UBERON:0004534	78.77	gold quality
amygdala	UBERON:0001876	78.52	gold quality
temporal lobe	UBERON:0001871	78.50	gold quality
metanephros cortex	UBERON:0010533	78.15	gold quality
left testis	UBERON:0004533	77.98	gold quality
Ammon’s horn	UBERON:0001954	77.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.75	gold quality
primary visual cortex	UBERON:0002436	77.43	gold quality
testis	UBERON:0000473	77.41	gold quality
body of uterus	UBERON:0009853	76.97	gold quality
mucosa of stomach	UBERON:0001199	76.64	gold quality
caudate nucleus	UBERON:0001873	76.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.96	gold quality
lower esophagus	UBERON:0013473	75.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	75.74	gold quality
tibial nerve	UBERON:0001323	75.70	gold quality
putamen	UBERON:0001874	74.98	gold quality
fallopian tube	UBERON:0003889	74.94	gold quality
adult mammalian kidney	UBERON:0000082	74.89	gold quality
left uterine tube	UBERON:0001303	74.82	gold quality
cortex of kidney	UBERON:0001225	74.81	gold quality
myometrium	UBERON:0001296	74.68	gold quality
islet of Langerhans	UBERON:0000006	74.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.40	gold quality
left adrenal gland cortex	UBERON:0035825	74.06	gold quality
ectocervix	UBERON:0012249	73.96	gold quality
granulocyte	CL:0000094	73.91	gold quality
tibial artery	UBERON:0007610	73.81	gold quality
popliteal artery	UBERON:0002250	73.80	gold quality
right adrenal gland	UBERON:0001233	73.72	gold quality
omental fat pad	UBERON:0010414	73.47	gold quality
left adrenal gland	UBERON:0001234	73.43	gold quality
prostate gland	UBERON:0002367	73.37	gold quality
right adrenal gland cortex	UBERON:0035827	73.27	gold quality
right coronary artery	UBERON:0001625	73.22	gold quality
spleen	UBERON:0002106	73.18	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.16	gold quality
adipose tissue	UBERON:0001013	73.15	gold quality
colon	UBERON:0001155	72.93	gold quality
right lung	UBERON:0002167	72.80	gold quality
uterine cervix	UBERON:0000002	72.60	gold quality
anatomical system	UBERON:0000467	72.47	gold quality
material anatomical entity	UBERON:0000465	72.41	gold quality
multicellular organism	UBERON:0000468	72.41	gold quality
transverse colon	UBERON:0001157	72.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.22	gold quality
intestine	UBERON:0000160	72.03	gold quality
left coronary artery	UBERON:0001626	71.66	gold quality
vagina	UBERON:0000996	71.32	gold quality
kidney	UBERON:0002113	71.29	gold quality
small intestine	UBERON:0002108	71.14	gold quality
fundus of stomach	UBERON:0001160	71.03	gold quality
right atrium auricular region	UBERON:0006631	71.03	gold quality
upper lobe of left lung	UBERON:0008952	70.90	gold quality
heart left ventricle	UBERON:0002084	70.88	gold quality
adrenal gland	UBERON:0002369	70.81	gold quality
ventricular zone	UBERON:0003053	70.62	gold quality
mammary gland	UBERON:0001911	70.25	gold quality
thoracic mammary gland	UBERON:0005200	70.25	gold quality
apex of heart	UBERON:0002098	70.13	gold quality
right lobe of liver	UBERON:0001114	70.01	gold quality
ganglionic eminence	UBERON:0004023	69.93	gold quality
heart	UBERON:0000948	69.88	gold quality
pancreas	UBERON:0001264	69.85	gold quality
endometrium	UBERON:0001295	69.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.54	gold quality
ascending aorta	UBERON:0001496	69.53	gold quality
thoracic aorta	UBERON:0001515	69.36	gold quality
urinary bladder	UBERON:0001255	69.08	gold quality
descending thoracic aorta	UBERON:0002345	68.95	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	46.3
Hypothalamus	tissue	25.6
Pituitary gland	tissue	22.7
Retina	tissue	20.4
Postcentral gyrus	tissue	18.7
Hippocampus	tissue	15.2	not detected
Septum	tissue	14.8
Pons	tissue	13.1
Prefrontal cortex	tissue	13.0
Cerebral cortex	tissue	13.0	low
Insular cortex	tissue	12.6
Hippocampal formation	tissue	11.9
Retrosplenial and cingulate cortex	tissue	11.9
Amygdala	tissue	11.4
Entorhinal cortex	tissue	11.0
Periaqueductal gray	tissue	11.0
Nucleus accumbens	tissue	10.9
Retrosplenial cortex	tissue	10.9
Frontal cortex	tissue	10.6
Substantia nigra	tissue	10.6
Temporal cortex	tissue	10.4
Motor cortex	tissue	10.3
Caudate putamen	tissue	10.0
Olfactory bulb	tissue	9.5
Somatosensory cortex	tissue	8.1
Ventral forebrain	tissue	8.0
Thalamus	tissue	7.7
Occipital cortex	tissue	7.7
Midbrain	tissue	7.6
Cerebellum	tissue	7.2	low
Epididymis	tissue	7.0	not detected
Medulla oblongata	tissue	5.9
Basal ganglia	tissue	5.5	not detected
Adrenal gland	tissue	5.4	low
Vagina	tissue	4.6	not detected
Choroid plexus	tissue	4.4
Superior colliculi	tissue	4.3
Endometrium 1	tissue	3.9	not detected
Seminal vesicle	tissue	3.8	not detected
Testis	tissue	3.7	medium
Ovary	tissue	3.5	not detected
Kidney	tissue	3.0	low
Fallopian tube	tissue	3.0	not detected
Putamen	tissue	2.6
Bone marrow	tissue	2.5	not detected
Cervix	tissue	2.4	not detected
Thyroid gland	tissue	2.3	not detected
Spinal cord	tissue	2.3
Spleen	tissue	1.9	not detected
Prostate	tissue	1.9	not detected
Smooth muscle	tissue	1.8	not detected
Gallbladder	tissue	1.8	not detected
Lymph node	tissue	1.7	not detected
Small intestine	tissue	1.7	medium
Thymus	tissue	1.7
Placenta	tissue	1.6	not detected
Rectum	tissue	1.5	medium
Lung	tissue	1.5	not detected
Skin 1	tissue	1.4	not detected
Corpus callosum	tissue	1.4

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Arcuate nucleus (56.7), Median raphe nucleus (47.6), Ventromedial nucleus (41.9), Lateral hypothalamic area (40.7), Dorsomedial nucleus (35.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CELF6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 55 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.15e-09, LOEUF 1.08, missense Z 0.23 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000287202 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
15:72,287,268–72,289,989	358 / 412.8	0.87	no
15:72,289,990–72,319,703	97 / 168.8	0.57	no
15:72,319,704–72,319,874	84 / 87.9	0.96	no

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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	celf6	ENSDARG00000101933
mus_musculus	Celf6	ENSMUSG00000032297
rattus_norvegicus	Celf6	ENSRNOG00000052224

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923433) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal emotion/affect behavior	1
abnormal response to novel odor	1
decreased dopamine level	1
decreased serotonin level	1
decreased noradrenaline level	1
decreased vocalization	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila melanogaster	P16914	100.0%	Diamond
Drosophila virilis	P23241	100.0%	Diamond
Pongo abelii	Q5NVC8	100.0%	Diamond
Gallus gallus	Q7T2T1	99.8%	Diamond
Drosophila erecta	B3NGA1	99.5%	Diamond
Drosophila yakuba	B4PIS2	99.5%	Diamond
Oryza sativa Indica Group	B8BCZ8	99.5%	Diamond
Oryza sativa Japonica Group	Q6K271	99.5%	Diamond
Bos taurus	Q2HJG2	99.0%	Diamond
Drosophila sechellia	B4HUE4	98.6%	Diamond
Drosophila simulans	B4QRJ0	98.6%	Diamond
Drosophila grimshawi	B4IX08	97.6%	Diamond
Macaca fascicularis	Q4R535	97.5%	Diamond
Xenopus tropicalis	A4IIM2	96.8%	Diamond
Xenopus laevis	Q7ZXE2	96.8%	Diamond
Drosophila mojavensis	B4KX02	96.3%	Diamond
Canis lupus familiaris	Q9XSR3	93.8%	Diamond
Drosophila ananassae	B3M3R5	92.1%	Diamond
Drosophila willistoni	B4MM23	90.1%	Diamond
Scheffersomyces stipitis CBS 6054	A3LXL0	85.7%	Diamond
Debaryomyces hansenii CBS767	Q6BI95	85.7%	Diamond
Candida albicans SC5314	Q5AI15	84.4%	Diamond
Chaetomium globosum CBS 148.51	Q2H0U6	79.9%	Diamond
Meyerozyma guilliermondii ATCC 6260	A5DM21	78.1%	Diamond
Arabidopsis thaliana	Q8VYM4	71.8%	Diamond
Plasmodium falciparum	P13824	65.7%	Diamond
Dictyostelium discoideum	Q54BM2	65.3%	Diamond
Saccharomyces cerevisiae S288C	Q00916	46.2%	Diamond
Mycosarcoma maydis	A0A0D1DWZ5	45.2%	Diamond
Schizosaccharomyces pombe 972h-	P36629	36.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
HEXA	protein-coding	3073
PKM	protein-coding	5315
PARP6	protein-coding	56965
HEXA-AS1	ncRNA	80072
TMEM202-AS1	ncRNA	105370888
TMEM202	protein-coding	338949
GRAMD2A	protein-coding	196996

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 by resolution:

PDB	Title	Method	Resolution (Å)
2DGQ	Solution structure of the N-terminal RNA binding domain in Bruno-like 6 RNA-binding …	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

13 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
regulation of alternative mRNA splicing, via spliceosome	BP	direct assay

Protein interactions and networks

STRING

showing 15 of 450 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELF6	RRM2	P31350	789
CELF6	CEBPD	P49716	788
CELF6	RRM1	P23921	761
CELF6	TNNT2	P45379	595
CELF6	LHFPL4	Q7Z7J7	485
CELF6	INSR	P06213	426
CELF6	OTUD7A	Q8TE49	418
CELF6	MBNL1	Q9NR56	417
CELF6	RBFOX1	Q9NWB1	404
CELF6	IQCF1	Q8N6M8	365
CELF6	RBM24	Q9BX46	361
CELF6	MBNL2	Q5VZF2	354
CELF6	RBM38	Q9H0Z9	349
CELF6	MBNL3	Q9NUK0	336
CELF6	NOVA1	P51513	304

IntAct

BioGRID (6 interactions; top human partners by supporting records): BTRC (Affinity Capture-Western; 3 records), CDKN1A (Affinity Capture-RNA), CRYBA1 (Two-hybrid), DYRK1A (Affinity Capture-MS)

SIGNOR signaling

2 signaling 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

Genetic variants

Variant evidence for CELF6: 70 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 1,227):

Position(s)	Effect	Δscore	Sites
15:72288302	donor_gain	1.0000
15:72288306–72288307	donor_loss	1.0000	5
15:72289508–72289509	acceptor_loss	1.0000	5
15:72289509–72289510	acceptor_gain	1.0000	2
15:72289625–72289626	donor_loss	1.0000	5
15:72289771–72289772	acceptor_loss	1.0000	3
15:72286363	acceptor_gain	0.9900
15:72287393–72287394	acceptor_loss	0.9900	4
15:72288452–72288453	acceptor_loss	0.9900	5
15:72288536–72288537	donor_loss	0.9900	5

AlphaMissense

1,312 missense substitutions predicted likely pathogenic (of 3,112 scored), across 278 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M140	9	0.971	0.998
M116	9	0.969	0.998
M457	9	0.892	0.996
F49	8	0.998	1.000
F439	8	0.998	1.000
F137	8	0.997	1.000
F399	8	0.997	1.000
H402	8	0.997	1.000
F416	8	0.996	1.000
D430	8	0.996	0.999
F441	8	0.996	1.000
F91	8	0.995	1.000
F178	8	0.995	1.000
F66	8	0.992	0.999
S436	8	0.987	1.000
S443	8	0.985	1.000
H108	8	0.984	0.991
D80	8	0.983	0.998
F154	8	0.983	0.999
F419	8	0.976	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.0002
Glioblastoma Multiforme (TCGA)	unfavorable	0.000437
Pancreatic Adenocarcinoma (TCGA)	favorable	0.000457

Disease associations

OMIM: gene MIM:612681 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST90000025_171	Appendicular lean mass	1e-10
GCST90011898_127	Alanine aminotransferase levels	5e-8
GCST008163_158	Height	1e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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	affects cotreatment, decreases methylation	1
aflatoxin B2	decreases methylation	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	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)

Via MONDO — disease-level, not drug-specific.