ELAVL4

Summary

ELAVL4 (ELAV like RNA binding protein 4, HGNC:3315) is a protein-coding gene on chromosome 1p33-p32.3, encoding ELAV-like protein 4 (P26378). RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs.

Enables mRNA 3’-UTR AU-rich region binding activity; poly(A) binding activity; and pre-mRNA intronic pyrimidine-rich binding activity. Involved in 3’-UTR-mediated mRNA stabilization; RNA processing; and positive regulation of 3’-UTR-mediated mRNA stabilization. Predicted to be located in axon; cytoplasm; and dendrite. Predicted to be part of ribonucleoprotein complex. Predicted to be active in glutamatergic synapse.

Source: NCBI Gene 1996 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_001144774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3315
Approved symbol	ELAVL4
Name	ELAV like RNA binding protein 4
Location	1p33-p32.3
Locus type	gene with protein product
Status	Approved
Aliases	PNEM
Ensembl gene	ENSG00000162374
Ensembl biotype	protein_coding
OMIM	168360
Entrez	1996

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000357083, ENST00000371819, ENST00000371821, ENST00000371823, ENST00000371824, ENST00000371827, ENST00000448907, ENST00000463650, ENST00000474675, ENST00000492299, ENST00000494555, ENST00000650764, ENST00000651258, ENST00000651347, ENST00000651693, ENST00000652252, ENST00000652274, ENST00000652353, ENST00000652693, ENST00000961724

RefSeq mRNA: 15 — MANE Select: NM_001144774 NM_001144774, NM_001144775, NM_001144776, NM_001144777, NM_001294348, NM_001324208, NM_001324209, NM_001324212, NM_001324213, NM_001324214, NM_001324215, NM_001324216, NM_001324217, NM_001410787, NM_021952

CCDS: CCDS44138, CCDS44139, CCDS44140, CCDS53315, CCDS553, CCDS72788, CCDS81321, CCDS90949, CCDS90950

Canonical transcript exons

ENST00000371824 — 7 exons

Exon	Start	End
ENSE00001064508	50144957	50145197
ENSE00001456203	50200851	50203772
ENSE00001456207	50108920	50109198
ENSE00001800957	50197429	50197467
ENSE00003469009	50177089	50177192
ENSE00003488239	50193765	50193918
ENSE00003661828	50195561	50195786

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.36.

FANTOM5 (CAGE): breadth broad, TPM avg 10.5584 / max 832.5096, expressed in 336 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2802	6.4869	256
2805	2.1395	242
2804	0.4436	136
2808	0.2737	70
2795	0.2026	67
2812	0.1910	43
2806	0.1646	72
2803	0.1359	65
2813	0.1262	33
2796	0.1089	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.36	gold quality
ganglionic eminence	UBERON:0004023	97.96	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.33	gold quality
middle temporal gyrus	UBERON:0002771	97.21	gold quality
cortical plate	UBERON:0005343	97.14	gold quality
pons	UBERON:0000988	96.99	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.93	gold quality
parietal lobe	UBERON:0001872	96.68	gold quality
postcentral gyrus	UBERON:0002581	96.58	gold quality
superior frontal gyrus	UBERON:0002661	96.51	gold quality
sperm	CL:0000019	96.39	gold quality
orbitofrontal cortex	UBERON:0004167	95.87	gold quality
dorsal root ganglion	UBERON:0000044	95.73	gold quality
superior vestibular nucleus	UBERON:0007227	95.24	gold quality
entorhinal cortex	UBERON:0002728	94.70	gold quality
occipital lobe	UBERON:0002021	94.14	gold quality
primary visual cortex	UBERON:0002436	94.04	gold quality
male germ cell	CL:0000015	93.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.85	gold quality
prefrontal cortex	UBERON:0000451	92.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.53	gold quality
substantia nigra pars compacta	UBERON:0001965	92.42	gold quality
frontal cortex	UBERON:0001870	92.06	gold quality
cerebral cortex	UBERON:0000956	91.30	gold quality
neocortex	UBERON:0001950	91.30	gold quality
trigeminal ganglion	UBERON:0001675	90.70	gold quality
CA1 field of hippocampus	UBERON:0003881	90.52	gold quality
medulla oblongata	UBERON:0001896	89.87	gold quality
embryo	UBERON:0000922	89.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.41	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1237.04
E-MTAB-9906	yes	1202.03
E-MTAB-11121	yes	898.59
E-HCAD-5	yes	35.17
E-MTAB-5061	yes	15.01
E-GEOD-93593	yes	14.69
E-CURD-114	yes	11.56
E-ENAD-27	yes	11.32
E-GEOD-83139	yes	9.55
E-ANND-3	yes	6.61
E-HCAD-10	yes	5.51
E-MTAB-10485	no	619.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NEUROG2

miRNA regulators (miRDB)

317 targeting ELAVL4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1252-5P	100.00	69.80	2774
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-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
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-4262	100.00	73.26	3931

Literature-anchored findings (GeneRIF, showing 36)

• HuD stabilizes the GAP-43 mRNA through a mechanism that is dependent on the length of the poly(A) tail and involves changes in its affinity for the mRNA (PMID:12034726)
• HuD expression in neuroblastoma (PMID:12209604)
• the importance of post-transcriptional mechanisms in regulating AChE expression in differentiating neurons and implicate HuD as a key trans-acting factor in these events (PMID:12468554)
• Ten HuD-derived peptides immunogenic in HLA-A*0201 restriction demonstrate in vitro binding to the HLA molecule, 8 elicit specific cytotoxic T lymphocytes (CTLs) in a murine model, 2 elicit specific human CTLs, and 1 is naturally processed and presented. (PMID:14512168)
• Significant T-cell activation occurred in response to 74% of the selected HuD peptides in Hu-positive patients, suggesting a role of cellular immunity during the course of anti-Hu syndrome. (PMID:15735910)
• potential role for ELAVL4 suggested as a modifier gene for age at onset of Parkinson’s disease (PMID:15827745)
• propose that haploinsufficiency of HuD due to chromosome #1p deletion in neuroblastoma selects for cells that amplify N-myc genes (PMID:16278682)
• Increased expression of HuD in the transgenic hippocampus is associated with a concomitant increase in acetylcholinesterase transcript levels. (PMID:17234598)
• HuD plays a role in the post-transcriptional control of GAP-43 mRNA (PMID:17577668)
• Gene silencing and overexpression of the nELAV member HuD in motoneuronal NSC34 cells indicate that Nova1 mRNA stability and translation are positively and strongly controlled by the nELAV proteins (PMID:18218628)
• an unregulated expression of HuD disrupts mossy fiber physiology in adult mice in part by altering the expression and phosphorylation of GAP-43 and the amount of free calmodulin available at the synaptic terminal (PMID:18493953)
• Association with rs967582 in a third cohort further implicates ELAVL4 as a Parkinson disease susceptibility gene. (PMID:18587682)
• increased level of mRNA transcripts detected in Small Cell Lung Cancer patients (PMID:18607064)
• We found no evidence for the presence of HuD-specific T cells in the cerebrospinal fluid of patients with Hu-associated paraneoplastic neurological syndromes. (PMID:19252764)
• alterations of nELAV genes could be involved in the onset and/or progression of a subset of neuroendocrine lung tumors. (PMID:19410329)
• Complexes of HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics: alphabeta T-cell receptor with self antigens is driven to engage HuD in the same traditional binding mode as Tax. (PMID:21282516)
• the endogenous function of ELAVL4 in relation to radiation sensitivity might be the regulation of cell proliferation and death (PMID:21491091)
• HuD is a pivotal regulator of insulin translation in pancreatic beta cells. (PMID:22387028)
• It can be involved in the pathogenesis of meningiomas in male patients. (PMID:22965691)
• found that p97 and its cofactor, UBXD8, destabilize p21, MKP-1, and SIRT1, three established mRNA targets of the RNA-binding protein HuR, by promoting release of HuR from mRNA (PMID:23618873)
• Phosphomimetic mutation at position Ser 221 increased nuclear HUD export. (PMID:23978401)
• Alzheimer’s disease brain tissues with elevated neuroserpin protein also showed increased expression of THRbeta1 and HuD (PMID:24036060)
• HuD binds to the APP and BACE1 3’ UTRs and increases APP and BACE1 levels. (PMID:24857657)
• study showed HuD is associated with histological grade, iffuse invasion and nodal metastasis in oral squamous cell carcinoma; it regulates expression of VEGF-A, VEGF-D, MMP-2 and MMP-9 (PMID:25278027)
• N-myc levels appear to be modulated by the antagonistic interactions of both miR-17, as a negative regulator, and HuD, as a positive regulator in N-myc-amplified neuroblastoma cells. (PMID:28560387)
• The high titres of HuD in SCLC patients and preferable consistency suggested that HuD may serve as a potential diagnostic criterium for SCLC and may serve as a marker of disease progression. (PMID:28739747)
• HuD enhanced p27 mRNA translation by interacting with both the 5’-untranslated region (UTR) and the 3’-UTR of p27 mRNA, and consequently suppressed cell cycle progression and growth of pancreatic neuroendocrine tumors. (PMID:30014466)
• the relative expression levels of Kv11.1 C-terminal isoforms are regulated by the RNA-binding HuR and HuD proteins (PMID:30377250)
• pathological mutations in FUS trigger an aberrant crosstalk with ELAVL4 with implications for Amyotrophic lateral sclerosis. (PMID:31242416)
• HuD regulates SOD1 expression during oxidative stress in differentiated neuroblastoma cells and sporadic ALS motor cortex. (PMID:33271327)
• HuB and HuD repress telomerase activity by dissociating HuR from TERC. (PMID:33589924)
• ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. (PMID:34314701)
• ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity. (PMID:34471224)
• RNA-binding protein ELAVL4/HuD ameliorates Alzheimer’s disease-related molecular changes in human iPSC-derived neurons. (PMID:35843356)
• Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases. (PMID:36498933)
• ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation. (PMID:37676718)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	elavl4	ENSDARG00000045639
mus_musculus	Elavl4	ENSMUSG00000028546
rattus_norvegicus	Elavl4	ENSRNOG00000023601
caenorhabditis_elegans		WBGENE00001368

Paralogs (24): ELAVL1 (ENSG00000066044), PABPC1 (ENSG00000070756), RBMS2 (ENSG00000076067), PABPC4 (ENSG00000090621), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), TARDBP (ENSG00000120948), HNRNPR (ENSG00000125944), RBM38 (ENSG00000132819), SYNCRIP (ENSG00000135316), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Protein

Protein identifiers

ELAV-like protein 4 — P26378 (reviewed: P26378)

Alternative names: Hu-antigen D, Paraneoplastic encephalomyelitis antigen HuD

All UniProt accessions (12): A0A0R4J2E6, A0A494BZW4, A0A494C011, A0A494C015, A0A494C0F8, A0A494C0M6, A0A494C0Q5, A0A494C147, A0A494C173, A0A494C1D9, B1APY9, P26378

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs. Plays a role in the regulation of mRNA stability, alternative splicing and translation. Binds to AU-rich element (ARE) sequences in the 3’ untranslated region (UTR) of target mRNAs, including GAP43, VEGF, FOS, CDKN1A and ACHE mRNA. Many of the target mRNAs are coding for RNA-binding proteins, transcription factors and proteins involved in RNA processing and/or neuronal development and function. By binding to the mRNA 3’UTR, decreases mRNA deadenylation and thereby contributes to the stabilization of mRNA molecules and their protection from decay. Also binds to the polyadenylated (poly(A)) tail in the 3’UTR of mRNA, thereby increasing its affinity for mRNA binding. Mainly plays a role in neuron-specific RNA processing by stabilization of mRNAs such as GAP43, ACHE and mRNAs of other neuronal proteins, thereby contributing to the differentiation of neural progenitor cells, nervous system development, learning and memory mechanisms. Involved in the negative regulation of the proliferative activity of neuronal stem cells and in the positive regulation of neuronal differentiation of neural progenitor cells. Promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone of the hippocampus by binding to and stabilizing SATB1 mRNA. Binds and stabilizes MSI1 mRNA in neural stem cells. Exhibits increased binding to ACHE mRNA during neuronal differentiation, thereby stabilizing ACHE mRNA and enhancing its expression. Protects CDKN1A mRNA from decay by binding to its 3’-UTR. May bind to APP and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization. Plays a role in neurite outgrowth and in the establishment and maturation of dendritic arbors, thereby contributing to neocortical and hippocampal circuitry function. Stabilizes GAP43 mRNA and protects it from decay during postembryonic development in the brain. By promoting the stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite outgrowth. Binds to BDNF long 3’UTR mRNA, thereby leading to its stabilization and increased dendritic translation after activation of PKC. By increasing translation of BDNF after nerve injury, may contribute to nerve regeneration. Acts as a stabilizing factor by binding to the 3’UTR of NOVA1 mRNA, thereby increasing its translation and enhancing its functional activity in neuron-specific splicing. Stimulates translation of mRNA in a poly(A)- and cap-dependent manner, possibly by associating with the EIF4F cap-binding complex. May also negatively regulate translation by binding to the 5’UTR of Ins2 mRNA, thereby repressing its translation. Upon glucose stimulation, Ins2 mRNA is released from ELAVL4 and translational inhibition is abolished. Also plays a role in the regulation of alternative splicing. May regulate alternative splicing of CALCA pre-mRNA into Calcitonin and Calcitonin gene-related peptide 1 (CGRP) by competing with splicing regulator TIAR for binding to U-rich intronic sequences of CALCA pre-mRNA.

Subunit / interactions. Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Associates with the EIF4F cap-binding complex, composed of EIF4G, EIF4A, EIF4E and PABP. Within the EIF4F cap-binding complex, interacts with EIF4A. Interacts with SMN (via Tudor domain) in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules. Interacts with MAP1 light chain LC1 (via C-terminus); the interaction contributes to the association of ELAVL4 with microtubules. Interacts with MAP1 light chain LC2.

Subcellular location. Cytoplasm. Perikaryon. Cell projection. Dendrite. Axon. Growth cone.

Tissue specificity. Expressed in pancreatic beta cells (at protein level). Expressed in the brain.

Post-translational modifications. Methylated by CARM1, which leads to reduced RNA-binding activity and enhanced interaction with SMN. Methylation at Arg-248 by CARM1 weakens protective binding to the 3’UTR of CDKN1A mRNA and down-regulates CDKN1A protein expression, thereby maintaining cells in a proliferative state. Methylation is inhibited by NGF, which facilitates neurite outgrowth.

Domain organisation. The RRM 3 domain is required for binding to poly(A) RNA, for the association with polysomes and with the EIF4F cap-binding complex and for the stimulation of translation. The RRM 1 and RRM 2 domains may contribute to polysome association and stimulation of translation.

Similarity. Belongs to the RRM elav family.

Isoforms (6)

UniProt ID	Names	Canonical?
P26378-6	6, Long	yes
P26378-1	1, HUD1PRO
P26378-2	2, HUD1
P26378-3	3, HUD4
P26378-4	4, HUD3
P26378-5	5

RefSeq proteins (15): NP_001138246, NP_001138247, NP_001138248, NP_001138249, NP_001281277, NP_001311137, NP_001311138, NP_001311141, NP_001311142, NP_001311143, NP_001311144, NP_001311145, NP_001311146, NP_001397716, NP_068771 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002343	Hud_Sxl_RNA	Family
IPR006548	ELAD_HU_SF	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034918	HuD_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (35 total): strand 8, helix 6, splice variant 5, modified residue 4, domain 3, sequence variant 3, turn 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1FXL	X-RAY DIFFRACTION	1.8
1G2E	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26378-F1	74.31	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 248, 38, 233, 248

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 433 (showing top): AHRARNT_01, GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, CREL_01, YAATNRNNNYNATT_UNKNOWN, GOBP_COGNITION, HNF3ALPHA_Q6, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, RORA1_01, GCANCTGNY_MYOD_Q6, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS

GO Biological Process (11): RNA processing (GO:0006396), mRNA processing (GO:0006397), learning (GO:0007612), locomotory behavior (GO:0007626), RNA splicing (GO:0008380), cerebral cortex neuron differentiation (GO:0021895), dendrite morphogenesis (GO:0048813), 3’-UTR-mediated mRNA stabilization (GO:0070935), positive regulation of 3’-UTR-mediated mRNA stabilization (GO:1905870), positive regulation of signal transduction (GO:0009967), negative regulation of gene expression (GO:0010629)

GO Molecular Function (8): mRNA 3’-UTR binding (GO:0003730), poly(A) binding (GO:0008143), mRNA 3’-UTR AU-rich region binding (GO:0035925), pre-mRNA intronic pyrimidine-rich binding (GO:0097158), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), axon (GO:0030424), dendrite (GO:0030425), growth cone (GO:0030426), perikaryon (GO:0043204), ribonucleoprotein complex (GO:1990904), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gene expression	2
RNA processing	2
binding	2
neuron projection	2
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
learning or memory	1
behavior	1
forebrain neuron differentiation	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
mRNA stabilization	1
positive regulation of gene expression	1
3’-UTR-mediated mRNA stabilization	1
regulation of 3’-UTR-mediated mRNA stabilization	1
signal transduction	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
mRNA binding	1
poly-purine tract binding	1
mRNA 3’-UTR binding	1
pre-mRNA intronic binding	1
nucleic acid binding	1
RNA binding	1
intracellular anatomical structure	1
dendritic tree	1
site of polarized growth	1
distal axon	1
neuronal cell body	1
protein-containing complex	1

Protein interactions and networks

STRING

2250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELAVL4	USP24	Q9UPU5	790
ELAVL4	CDCP2	Q5VXM1	763
ELAVL4	HIVEP3	Q5T1R4	729
ELAVL4	KHSRP	Q92945	698
ELAVL4	EIF4A1	P04765	693
ELAVL4	EIF4A2	Q14240	693
ELAVL4	NOVA1	P51513	687
ELAVL4	DHX36	Q9H2U1	675
ELAVL4	IGF2BP1	Q9NZI8	668
ELAVL4	NXF1	Q9UBU9	651
ELAVL4	FMR1	Q06787	648
ELAVL4	BACE1	P56817	615
ELAVL4	SMN1	Q16637	608
ELAVL4	MYCN	P04198	605
ELAVL4	APP	P05067	587

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
FBXW11	AHCYL1	psi-mi:“MI:0914”(association)	0.530
SART3	NSA2	psi-mi:“MI:0914”(association)	0.530
ADAMTS18	ALB	psi-mi:“MI:0914”(association)	0.530
ELAVL2	CASC3	psi-mi:“MI:0914”(association)	0.530
ELAVL4	EYA3	psi-mi:“MI:0915”(physical association)	0.400
ELAVL4	PHF20L1	psi-mi:“MI:0915”(physical association)	0.370
ELAVL4	EWSR1	psi-mi:“MI:0915”(physical association)	0.370
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CEP135	WDR91	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
CHD8	IGLV4-60	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
RIMS1	PSMD12	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
RNF41	SHTN1	psi-mi:“MI:0914”(association)	0.350
PNRC2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
GOLGA8A	ZNF320	psi-mi:“MI:0914”(association)	0.350
RPL19		psi-mi:“MI:0914”(association)	0.350
FAU		psi-mi:“MI:0914”(association)	0.350

BioGRID (56): ELAVL4 (Affinity Capture-MS), EWSR1 (Two-hybrid), ELAVL4 (Affinity Capture-MS), Hnrnph1 (Reconstituted Complex), Sfpq (Reconstituted Complex), G3bp1 (Reconstituted Complex), Igf2bp1 (Reconstituted Complex), IGF2BP1 (Affinity Capture-Western), ELAVL4 (Affinity Capture-MS), ELAVL4 (Affinity Capture-MS), ELAVL4 (Affinity Capture-MS), ELAVL4 (Affinity Capture-MS), ELAVL4 (Affinity Capture-MS), NXF1 (Affinity Capture-Western), NXF1 (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IEW8, A4QNI8, B5DF91, O01671, O09032, O17310, O61374, O64380, O95758, O97018, P16914, P19339, P26378, P26599, P42731, P70372, P86049, Q12926, Q14576, Q15717, Q1JQ73, Q24668, Q28FX0, Q28GD4, Q29099, Q5R9H4, Q5R9Z6, Q5U259, Q5YD48, Q60899, Q60900, Q61701, Q6DEY7, Q6GLB5, Q6GR16, Q6YZW2, Q7SZT7, Q8CH84, Q8GZ26, Q8LFS6

Diamond homologs: A0A0R4IEW8, A4QNI8, A8NS61, A8WLV5, B3M3R5, B3NGA1, B4HUE4, B4IX08, B4KX02, B4LFQ9, B4MM23, B4PIS2, B4QRJ0, B5DF91, B8BCZ8, O01671, O04425, O09032, O17310, O61374, O75821, O89086, O97018, P16914, P19339, P19683, P23241, P26378, P28644, P29558, P49310, P60824, P60825, P60826, P70372, P98179, Q04836, Q12926, Q14011, Q14498

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ELAVL4	“up-regulates quantity”	ADAM10	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1224 predictions. Top by Δscore:

Variant	Effect	Δscore
1:50193918:GGT:G	donor_gain	1.0000
1:50193920:T:G	donor_gain	1.0000
1:50195558:CA:C	acceptor_loss	1.0000
1:50195559:A:AG	acceptor_gain	1.0000
1:50195559:AG:A	acceptor_gain	1.0000
1:50195560:G:GG	acceptor_gain	1.0000
1:50195560:G:T	acceptor_loss	1.0000
1:50195560:GG:G	acceptor_gain	1.0000
1:50195560:GGA:G	acceptor_gain	1.0000
1:50195560:GGAGT:G	acceptor_gain	1.0000
1:50195782:TTC:T	donor_gain	1.0000
1:50195782:TTCAG:T	donor_loss	1.0000
1:50195785:AGGTA:A	donor_loss	1.0000
1:50195786:GGT:G	donor_loss	1.0000
1:50195787:GT:G	donor_loss	1.0000
1:50195788:T:A	donor_loss	1.0000
1:50109961:GATG:G	donor_gain	0.9900
1:50109962:ATGGT:A	donor_loss	0.9900
1:50109964:GGTA:G	donor_loss	0.9900
1:50109965:G:GC	donor_loss	0.9900
1:50109965:G:GG	donor_gain	0.9900
1:50109966:T:TC	donor_loss	0.9900
1:50144952:TTTA:T	acceptor_loss	0.9900
1:50144953:TTAG:T	acceptor_loss	0.9900
1:50144954:TA:T	acceptor_loss	0.9900
1:50144955:A:AG	acceptor_gain	0.9900
1:50144955:A:C	acceptor_loss	0.9900
1:50144956:G:GG	acceptor_gain	0.9900
1:50144956:G:GT	acceptor_loss	0.9900
1:50144956:GAT:G	acceptor_gain	0.9900

AlphaMissense

2431 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:50145084:C:T	T51I	1.000
1:50145086:A:G	N52D	1.000
1:50145088:C:A	N52K	1.000
1:50145088:C:G	N52K	1.000
1:50145089:C:T	L53F	1.000
1:50145090:T:A	L53H	1.000
1:50145090:T:C	L53P	1.000
1:50145090:T:G	L53R	1.000
1:50145093:T:A	I54N	1.000
1:50145093:T:C	I54T	1.000
1:50145093:T:G	I54S	1.000
1:50145095:G:T	V55F	1.000
1:50145096:T:A	V55D	1.000
1:50145098:A:C	N56H	1.000
1:50145098:A:G	N56D	1.000
1:50145100:C:A	N56K	1.000
1:50145100:C:G	N56K	1.000
1:50145101:T:C	Y57H	1.000
1:50145101:T:G	Y57D	1.000
1:50145102:A:G	Y57C	1.000
1:50145105:T:C	L58S	1.000
1:50145107:C:A	P59T	1.000
1:50145107:C:T	P59S	1.000
1:50145108:C:A	P59H	1.000
1:50145108:C:G	P59R	1.000
1:50145108:C:T	P59L	1.000
1:50145141:T:C	L70P	1.000
1:50145143:T:A	F71I	1.000
1:50145143:T:C	F71L	1.000
1:50145143:T:G	F71V	1.000

dbSNP variants (sampled 300 via entrez): RS1000016218 (1:50159631 G>A,C), RS1000036171 (1:50201742 T>C), RS1000040766 (1:50066645 T>G), RS1000045948 (1:50160572 G>C,T), RS1000054716 (1:50194161 T>G), RS1000088776 (1:50055879 A>G), RS1000114076 (1:50171676 C>T), RS1000119998 (1:50056292 G>A,C,T), RS1000155666 (1:50060918 A>G), RS1000166254 (1:50156280 A>G), RS1000171315 (1:50120761 C>A), RS1000173078 (1:50050911 C>T), RS1000195662 (1:50063631 T>C), RS1000233649 (1:50187457 A>G), RS1000260107 (1:50155061 T>A)

Disease associations

OMIM: gene MIM:168360 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001762_885	Obesity-related traits	6.000000e-06
GCST002783_444	Body mass index	6.000000e-09
GCST002783_520	Body mass index	1.000000e-08
GCST004495_25	BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004495_26	BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004495_27	BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004497_122	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004497_123	Body mass index (joint analysis main effects and smoking interaction)	9.000000e-06
GCST004497_124	Body mass index (joint analysis main effects and smoking interaction)	9.000000e-06
GCST006661_33	Male-pattern baldness	9.000000e-12
GCST006802_7	Body mass index	4.000000e-06
GCST007201_48	Schizophrenia	1.000000e-07
GCST007327_164	Smoking status (ever vs never smokers)	1.000000e-10
GCST008529_27	Tea consumption	3.000000e-06
GCST008757_48	Alcohol consumption	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005118	IGFBP-1 measurement
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
sodium arsenite	affects methylation, increases expression	2
1-Methyl-4-phenylpyridinium	decreases expression, affects expression, affects reaction	2
ascorbate-2-phosphate	increases expression, affects binding, affects cotreatment	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects reaction, affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Chir 99021	affects cotreatment, decreases expression, affects binding, increases expression	1
MRK 003	increases expression	1
bisphenol S	decreases methylation	1
XAV939	affects binding, affects cotreatment, increases expression, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, decreases expression	1
Ascorbic Acid	affects binding, affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Hydrocortisone	affects cotreatment, decreases expression	1
Mitoxantrone	affects response to substance	1
Phthalic Acids	affects methylation	1
Tretinoin	increases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1SB	Abcam U-87MG ELAVL4 KO	Cancer cell line	Male
CVCL_D8G4	Ubigene H1 ELAVL4 KO	Embryonic stem cell	Male

Clinical trials (associated diseases)

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