CELF4

Summary

CELF4 (CUGBP Elav-like family member 4, HGNC:14015) is a protein-coding gene on chromosome 18q12.2, encoding CUGBP Elav-like family member 4 (Q9BZC1). 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 transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 56853 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 36
• Clinical variants (ClinVar): 117 total
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_020180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14015
Approved symbol	CELF4
Name	CUGBP Elav-like family member 4
Location	18q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101489
Ensembl biotype	protein_coding
OMIM	612679
Entrez	56853

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 41 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000334919, ENST00000361795, ENST00000420428, ENST00000586009, ENST00000587074, ENST00000587449, ENST00000587657, ENST00000587819, ENST00000587911, ENST00000587924, ENST00000588591, ENST00000588597, ENST00000589229, ENST00000589386, ENST00000590011, ENST00000590112, ENST00000591282, ENST00000591287, ENST00000591421, ENST00000593271, ENST00000601019, ENST00000601392, ENST00000603232, ENST00000899355, ENST00000899356, ENST00000899357, ENST00000899358, ENST00000899359, ENST00000899360, ENST00000899361, ENST00000899362, ENST00000899363, ENST00000899364, ENST00000899365, ENST00000931906, ENST00000970536, ENST00000970537, ENST00000970538, ENST00000970539, ENST00000970540, ENST00000970541, ENST00000970542, ENST00000970543, ENST00000970544, ENST00000970545, ENST00000970546

RefSeq mRNA: 70 — MANE Select: NM_020180 NM_001025087, NM_001025088, NM_001025089, NM_001330603, NM_001353695, NM_001353696, NM_001353697, NM_001353698, NM_001353699, NM_001353700, NM_001353702, NM_001353703, NM_001353705, NM_001353706, NM_001353707, NM_001353708, NM_001353709, NM_001353710, NM_001353711, NM_001353712, NM_001353713, NM_001353714, NM_001353715, NM_001353716, NM_001353717, NM_001353718, NM_001353719, NM_001353720, NM_001353721, NM_001353722, NM_001353723, NM_001353724, NM_001353725, NM_001353726, NM_001353727, NM_001353728, NM_001353729, NM_001353730, NM_001353731, NM_001353732, NM_001353733, NM_001353734, NM_001353735, NM_001353736, NM_001353737, NM_001353738, NM_001353739, NM_001353740, NM_001353741, NM_001353742, NM_001353743, NM_001353744, NM_001353745, NM_001353746, NM_001353747, NM_001353748, NM_001353749, NM_001353750, NM_001353751, NM_001353752, NM_001353753, NM_001353754, NM_001353755, NM_001353756, NM_001353757, NM_001353758, NM_001353759, NM_001353760, NM_001353761, NM_020180

CCDS: CCDS32818, CCDS45856, CCDS45857, CCDS45858, CCDS82250

Canonical transcript exons

ENST00000420428 — 13 exons

Exon	Start	End
ENSE00002725604	37565356	37565798
ENSE00003469310	37485525	37485607
ENSE00003475741	37266533	37266598
ENSE00003485344	37259181	37259264
ENSE00003506464	37270768	37270917
ENSE00003569898	37273016	37273163
ENSE00003632296	37264674	37264757
ENSE00003658067	37253767	37253938
ENSE00003847371	37243040	37245197
ENSE00003889351	37275115	37275243
ENSE00003889387	37274311	37274454
ENSE00003891907	37321803	37321881
ENSE00003892208	37274805	37274884

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 97.29.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0549 / max 1047.8138, expressed in 310 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171723	2.6440	137
171722	0.7488	103
171705	0.3728	137
171725	0.3664	104
171720	0.2990	88
171712	0.1781	92
171713	0.1676	61
171721	0.1316	60
171724	0.0657	39
171718	0.0429	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	97.29	gold quality
cerebellar hemisphere	UBERON:0002245	97.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.08	gold quality
primary visual cortex	UBERON:0002436	97.01	gold quality
cerebellum	UBERON:0002037	96.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.66	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.55	gold quality
right frontal lobe	UBERON:0002810	96.50	gold quality
anterior cingulate cortex	UBERON:0009835	96.40	gold quality
prefrontal cortex	UBERON:0000451	96.35	gold quality
frontal cortex	UBERON:0001870	96.21	gold quality
neocortex	UBERON:0001950	95.87	gold quality
superior frontal gyrus	UBERON:0002661	95.83	gold quality
occipital lobe	UBERON:0002021	95.66	gold quality
nucleus accumbens	UBERON:0001882	95.58	gold quality
cerebral cortex	UBERON:0000956	95.43	gold quality
entorhinal cortex	UBERON:0002728	95.33	gold quality
amygdala	UBERON:0001876	95.29	gold quality
hypothalamus	UBERON:0001898	95.29	gold quality
temporal lobe	UBERON:0001871	95.16	gold quality
cerebellar vermis	UBERON:0004720	95.14	gold quality
postcentral gyrus	UBERON:0002581	94.60	gold quality
substantia nigra pars compacta	UBERON:0001965	94.53	gold quality
parietal lobe	UBERON:0001872	94.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.39	gold quality
middle temporal gyrus	UBERON:0002771	94.36	gold quality
brain	UBERON:0000955	94.01	gold quality
forebrain	UBERON:0001890	93.99	gold quality
Ammon’s horn	UBERON:0001954	93.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	954.02
E-MTAB-11121	yes	690.43
E-HCAD-5	yes	519.48
E-GEOD-75140	yes	90.69
E-HCAD-35	yes	63.73
E-HCAD-25	yes	36.94
E-GEOD-93593	yes	16.57
E-GEOD-137537	yes	11.04
E-GEOD-84465	yes	7.06
E-ANND-3	yes	4.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting CELF4, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 6)

• Determination of CELF4 protein domains required for RNA splicing. (PMID:14973222)
• validated occurrence of an unusual TG 3’ splice site in intron 6 (PMID:17672918)
• Authors report a modifying effect of a polymorphism of CELF4 on the dose-dependent association between anthracyclines and cardiomyopathy, which possibly occurs through a pathway that involves the expression of abnormally spliced TNNT2 variants. (PMID:26811534)
• The present study refines the molecular and neuropsychiatric phenotype associated with 18q12.2 deletion leading to CELF4 haploinsufficiency and provides evidence for a role for CELF4 in brain development and autism spectrum disorders. (PMID:28407444)
• An intronic variant in the CELF4 gene is associated with risk for colorectal cancer. (PMID:33930674)
• Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex. (PMID:37758766)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	celf4	ENSDARG00000070045
mus_musculus	Celf4	ENSMUSG00000024268
rattus_norvegicus	Celf4	ENSRNOG00000014503
drosophila_melanogaster	bru1	FBGN0000114
drosophila_melanogaster	Pof	FBGN0035047
drosophila_melanogaster	bru2	FBGN0262475
caenorhabditis_elegans		WBGENE00017135
caenorhabditis_elegans		WBGENE00017140
caenorhabditis_elegans		WBGENE00020354

Paralogs (6): CELF2 (ENSG00000048740), RBM28 (ENSG00000106344), CELF6 (ENSG00000140488), CELF1 (ENSG00000149187), CELF3 (ENSG00000159409), CELF5 (ENSG00000161082)

Protein

Protein identifiers

CUGBP Elav-like family member 4 — Q9BZC1 (reviewed: Q9BZC1)

Alternative names: Bruno-like protein 4, CUG-BP- and ETR-3-like factor 4, RNA-binding protein BRUNOL-4

All UniProt accessions (14): Q9BZC1, A0A0A0MTT3, A0A0C4DGR1, B4DHA8, K7EJ26, K7EJD7, K7EJK3, K7EJW4, K7ENR2, K7EPX2, K7EQ97, K7ERH1, M0QY66, M0R137

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. Promotes exclusion of both the smooth muscle (SM) and non-muscle (NM) exons in actinin pre-mRNAs. Activates the splicing of MAPT/Tau exon 10. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitous. Strongly expressed in the cerebellum, hippocampus, amygdala, temporal and frontal cortex and frontal lobes.

Similarity. Belongs to the CELF/BRUNOL family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BZC1-1	1	yes
Q9BZC1-2	2
Q9BZC1-3	3
Q9BZC1-4	4
Q9BZC1-5	5

RefSeq proteins (70): NP_001020258, NP_001020259, NP_001020260, NP_001317532, NP_001340624, NP_001340625, NP_001340626, NP_001340627, NP_001340628, NP_001340629, NP_001340631, NP_001340632, NP_001340634, NP_001340635, NP_001340636, NP_001340637, NP_001340638, NP_001340639, NP_001340640, NP_001340641, NP_001340642, NP_001340643, NP_001340644, NP_001340645, NP_001340646, NP_001340647, NP_001340648, NP_001340649, NP_001340650, NP_001340651, NP_001340652, NP_001340653, NP_001340654, NP_001340655, NP_001340656, NP_001340657, NP_001340658, NP_001340659, NP_001340660, NP_001340661, NP_001340662, NP_001340663, NP_001340664, NP_001340665, NP_001340666, NP_001340667, NP_001340668, NP_001340669, NP_001340670, NP_001340671, NP_001340672, NP_001340673, NP_001340674, NP_001340675, NP_001340676, NP_001340677, NP_001340678, NP_001340679, NP_001340680, NP_001340681, NP_001340682, NP_001340683, NP_001340684, NP_001340685, NP_001340686, NP_001340687, NP_001340688, NP_001340689, NP_001340690, NP_064565* (*=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 (35 total): strand 9, splice variant 5, sequence conflict 4, helix 4, region of interest 4, domain 3, turn 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2DGP	SOLUTION NMR
2DNK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZC1-F1	62.70	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 278 (showing top): GGGACCA_MIR133A_MIR133B, RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GCANCTGNY_MYOD_Q6, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MEF2_02, GGGTGGRR_PAX4_03, GCGCTTT_MIR518B_MIR518C_MIR518D

GO Biological Process (15): alternative mRNA splicing, via spliceosome (GO:0000380), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), in utero embryonic development (GO:0001701), mRNA splice site recognition (GO:0006376), germ cell development (GO:0007281), embryo development ending in birth or egg hatching (GO:0009792), negative regulation of mRNA splicing, via spliceosome (GO:0048025), positive regulation of mRNA splicing, via spliceosome (GO:0048026), excitatory postsynaptic potential (GO:0060079), negative regulation of excitatory postsynaptic potential (GO:0090394), regulation of retina development in camera-type eye (GO:1902866), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of translation (GO:0017148)

GO Molecular Function (7): mRNA regulatory element binding translation repressor activity (GO:0000900), mRNA binding (GO:0003729), pre-mRNA binding (GO:0036002), BRE binding (GO:0042835), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), postsynapse (GO:0098794), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA splicing, via spliceosome	3
regulation of mRNA splicing, via spliceosome	3
RNA binding	3
cellular anatomical structure	3
RNA processing	2
binding	2
alternative mRNA splicing, via spliceosome	1
chordate embryonic development	1
spliceosomal complex assembly	1
protein-RNA complex assembly	1
developmental process involved in reproduction	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
embryo development	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
positive regulation of RNA splicing	1
positive regulation of mRNA processing	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
negative regulation of biological process	1
excitatory postsynaptic potential	1
modulation of excitatory postsynaptic potential	1
regulation of developmental process	1
retina development in camera-type eye	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
mRNA binding	1
translation repressor activity	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
synapse	1

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELF4	CEBPD	P49716	891
CELF4	BICD1	Q96G01	838
CELF4	DDX11	Q96FC9	768
CELF4	TNNT2	P45379	696
CELF4	PIK3C3	Q8NEB9	682
CELF4	PLEKHB2	Q96CS7	608
CELF4	MBNL3	Q9NUK0	573
CELF4	MBNL2	Q5VZF2	572
CELF4	RBFOX1	Q9NWB1	555
CELF4	CLCN1	P35523	520
CELF4	MBNL1	Q9NR56	500
CELF4	RBFOX2	O43251	475
CELF4	CELF2	O95319	459
CELF4	LUZP4	Q9P127	441
CELF4	NOVA1	P51513	419

IntAct

1 interactions, top by confidence:

BioGRID (13): TIAL1 (Two-hybrid), RBPMS2 (Two-hybrid), PCBP3 (Two-hybrid), PRR20B (Two-hybrid), PRR20A (Two-hybrid), PRR20D (Two-hybrid), PRR20C (Two-hybrid), PRR20E (Two-hybrid), CELF4 (Two-hybrid), AUP1 (Affinity Capture-MS), LPCAT1 (Affinity Capture-MS), MSI2 (Affinity Capture-MS), APP (Reconstituted Complex)

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: A0A8M1NHK4, A0AV96, A0JM51, A1D4K4, A2Q848, A4FV72, O01671, O04425, O43040, O43390, O60506, P25299, P33240, P49314, P86049, Q08937, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q15020, Q28IQ9, Q2UK72, Q4R2Z0, Q4R535, Q4WK03, Q54PB2, Q5NVC8, Q5R5P4, Q5R723, Q5R9H4, Q5RDA3, Q5REG1, Q5SZQ8, Q5YD48, Q66H68, Q6CEW9, Q6DCB7, Q6DGV1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CELF4	“up-regulates quantity”	TNNT2	“post transcriptional regulation”
CELF4	up-regulates	Excitatory_synaptic_transmission

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	17
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3646 predictions. Top by Δscore:

Variant	Effect	Δscore
18:37253762:GTTAC:G	donor_loss	1.0000
18:37253763:TTA:T	donor_loss	1.0000
18:37253764:TACC:T	donor_loss	1.0000
18:37253765:A:T	donor_loss	1.0000
18:37253766:C:CA	donor_loss	1.0000
18:37264803:G:GC	acceptor_gain	1.0000
18:37264811:A:T	acceptor_gain	1.0000
18:37270930:A:C	acceptor_gain	1.0000
18:37273011:CTCA:C	donor_loss	1.0000
18:37273013:CA:C	donor_loss	1.0000
18:37273014:ACCT:A	donor_loss	1.0000
18:37273015:C:CG	donor_loss	1.0000
18:37273159:ATCAG:A	acceptor_gain	1.0000
18:37273160:TCAG:T	acceptor_gain	1.0000
18:37273161:CAG:C	acceptor_gain	1.0000
18:37273161:CAGC:C	acceptor_gain	1.0000
18:37273162:AG:A	acceptor_gain	1.0000
18:37273162:AGCT:A	acceptor_loss	1.0000
18:37273163:GCT:G	acceptor_loss	1.0000
18:37273164:C:CC	acceptor_gain	1.0000
18:37273170:C:CT	acceptor_gain	1.0000
18:37273171:A:T	acceptor_gain	1.0000
18:37274304:CACTT:C	donor_loss	1.0000
18:37274305:ACTTA:A	donor_loss	1.0000
18:37274308:TA:T	donor_loss	1.0000
18:37274309:A:AC	donor_gain	1.0000
18:37274309:AC:A	donor_loss	1.0000
18:37274309:ACTG:A	donor_gain	1.0000
18:37274309:ACTGC:A	donor_gain	1.0000
18:37274310:C:CC	donor_gain	1.0000

AlphaMissense

3235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:37253857:A:G	L472P	1.000
18:37253857:A:T	L472H	1.000
18:37253896:A:T	I459N	1.000
18:37253899:G:T	A458D	1.000
18:37259192:A:G	F441S	1.000
18:37259204:A:G	L437P	1.000
18:37259231:A:G	L428P	1.000
18:37259231:A:T	L428Q	1.000
18:37259235:G:C	H427D	1.000
18:37259238:A:C	Y426D	1.000
18:37259238:A:G	Y426H	1.000
18:37259240:A:T	I425N	1.000
18:37259243:A:G	F424S	1.000
18:37259246:A:G	L423P	1.000
18:37259246:A:T	L423Q	1.000
18:37259248:G:C	N422K	1.000
18:37259248:G:T	N422K	1.000
18:37274396:C:G	R239P	1.000
18:37274405:C:G	R236P	1.000
18:37274406:G:T	R236S	1.000
18:37274421:C:G	D231H	1.000
18:37274423:G:T	A230D	1.000
18:37274428:C:A	K228N	1.000
18:37274428:C:G	K228N	1.000
18:37274430:T:C	K228E	1.000
18:37274432:A:T	V227D	1.000
18:37274438:A:G	L225P	1.000
18:37274827:A:G	L212P	1.000
18:37274839:G:T	A208D	1.000
18:37274840:C:G	A208P	1.000

dbSNP variants (sampled 300 via entrez): RS1000021963 (18:37468228 G>A), RS1000036070 (18:37430660 T>C,G), RS1000044604 (18:37271638 T>A), RS1000050748 (18:37346938 A>C), RS1000051468 (18:37385728 T>C), RS1000060521 (18:37265950 C>G,T), RS1000068345 (18:37503709 C>T), RS1000080872 (18:37385390 G>A,T), RS1000081158 (18:37551517 C>T), RS1000090418 (18:37501259 A>G), RS1000111171 (18:37431967 G>A,T), RS1000112029 (18:37316356 G>A), RS1000119214 (18:37345864 C>G,T), RS1000127170 (18:37267249 G>A,T), RS1000128567 (18:37310813 C>G,T)

Disease associations

OMIM: gene MIM:612679 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Definitive	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (3): myoepithelial tumor (MONDO:0002380), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000201_5	Response to iloperidone treatment (QT prolongation)	3.000000e-06
GCST000376_1	Telomere length	3.000000e-06
GCST002337_164	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST002367_5	Social communication problems	5.000000e-06
GCST002598_23	Educational attainment	3.000000e-07
GCST002711_12	Sleep duration	5.000000e-06
GCST003262_589	Post bronchodilator FEV1	4.000000e-07
GCST003264_1582	Post bronchodilator FEV1/FVC ratio	4.000000e-08
GCST003447_9	Neuroticism	1.000000e-08
GCST003770_33	Neuroticism	2.000000e-08
GCST003770_65	Neuroticism	6.000000e-09
GCST005835_7	Remission after SSRI treatment in MDD or neuroticism	4.000000e-08
GCST006940_25	Neurociticism	4.000000e-21
GCST006943_49	Feeling miserable	2.000000e-10
GCST006944_68	Experiencing mood swings	9.000000e-12
GCST006945_17	Feeling guilty	4.000000e-10
GCST006946_18	Worry too long after an embarrassing experience	4.000000e-11
GCST006947_26	Feeling fed-up	4.000000e-13
GCST006951_27	Feeling hurt	4.000000e-16
GCST007576_159	Chronotype	4.000000e-09
GCST007709_115	General factor of neuroticism	4.000000e-13
GCST007709_116	General factor of neuroticism	6.000000e-13
GCST007709_146	General factor of neuroticism	1.000000e-08
GCST008157_11	Body fat mass	7.000000e-06
GCST008357_27	Mood instability	7.000000e-10
GCST008595_218	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	6.000000e-15
GCST009523_62	Household income	2.000000e-08
GCST009523_63	Household income	2.000000e-09
GCST009524_270	Household income (MTAG)	3.000000e-09
GCST009524_298	Household income (MTAG)	1.000000e-09

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment
EFO:0004784	self reported educational attainment
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0007660	neuroticism measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0009598	feeling miserable measurement
EFO:0008475	mood instability measurement
EFO:0009595	guilt measurement
EFO:0009589	worry measurement
EFO:0009588	feeling “fed-up” measurement
EFO:0009599	feeling emotionally hurt measurement
EFO:0008328	chronotype measurement
EFO:0004337	intelligence
EFO:0009695	household income
EFO:0007828	daytime rest measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4799915	Toxicity	3	iloperidone	Acquired Long QT Syndrome (aLQTS)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4799915	CELF4	3	0.00	1	iloperidone
rs1786814	CELF4		0.00	0

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects methylation, affects cotreatment, decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Methapyrilene	affects methylation	1
Phthalic Acids	decreases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Triclosan	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

209 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
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
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