IGF2BP3

Summary

IGF2BP3 (insulin like growth factor 2 mRNA binding protein 3, HGNC:28868) is a protein-coding gene on chromosome 7p15.3, encoding Insulin-like growth factor 2 mRNA-binding protein 3 (O00425). RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs).

The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5’ UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes.

Source: NCBI Gene 10643 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_006547

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28868
Approved symbol	IGF2BP3
Name	insulin like growth factor 2 mRNA binding protein 3
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	IMP-3, CT98, IMP3
Ensembl gene	ENSG00000136231
Ensembl biotype	protein_coding
OMIM	608259
Entrez	10643

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding_CDS_not_defined, 6 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000258729, ENST00000421467, ENST00000465058, ENST00000466809, ENST00000467592, ENST00000468005, ENST00000468263, ENST00000469723, ENST00000474105, ENST00000476938, ENST00000479504, ENST00000480547, ENST00000491719, ENST00000492771, ENST00000495009, ENST00000497563, ENST00000498363, ENST00000619562, ENST00000922496

RefSeq mRNA: 1 — MANE Select: NM_006547 NM_006547

CCDS: CCDS5382

Canonical transcript exons

ENST00000258729 — 15 exons

Exon	Start	End
ENSE00001887310	23469936	23470491
ENSE00003227662	23310209	23312460
ENSE00003481414	23342064	23342189
ENSE00003501220	23361690	23361741
ENSE00003551236	23312735	23312848
ENSE00003557166	23347600	23347734
ENSE00003559493	23313522	23313653
ENSE00003563138	23317639	23317713
ENSE00003570607	23418776	23418824
ENSE00003580576	23361534	23361597
ENSE00003598041	23343718	23343853
ENSE00003599376	23468482	23468542
ENSE00003612459	23345940	23346062
ENSE00003651453	23351305	23351586
ENSE00003665881	23319138	23319254

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6623 / max 673.4212, expressed in 1474 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83116	20.2479	1174
83118	5.2698	974
83108	2.6814	600
83107	2.2437	555
83117	0.6593	364
83115	0.6239	232
83119	0.3031	145
83106	0.2852	159
83113	0.1760	71
83112	0.1172	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.63	gold quality
amniotic fluid	UBERON:0000173	97.23	gold quality
oocyte	CL:0000023	96.35	gold quality
adrenal tissue	UBERON:0018303	96.13	gold quality
buccal mucosa cell	CL:0002336	93.99	gold quality
placenta	UBERON:0001987	93.77	gold quality
embryo	UBERON:0000922	91.32	gold quality
sperm	CL:0000019	90.70	gold quality
ventricular zone	UBERON:0003053	88.62	gold quality
ganglionic eminence	UBERON:0004023	87.94	gold quality
male germ cell	CL:0000015	87.20	gold quality
monocyte	CL:0000576	85.16	gold quality
cartilage tissue	UBERON:0002418	84.79	gold quality
mononuclear cell	CL:0000842	84.40	gold quality
cortical plate	UBERON:0005343	83.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.68	gold quality
leukocyte	CL:0000738	83.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.38	gold quality
esophagus squamous epithelium	UBERON:0006920	80.16	gold quality
pigmented layer of retina	UBERON:0001782	77.59	gold quality
decidua	UBERON:0002450	76.81	gold quality
epithelium of esophagus	UBERON:0001976	76.10	gold quality
epithelium of nasopharynx	UBERON:0001951	75.99	gold quality
sural nerve	UBERON:0015488	75.49	gold quality
stromal cell of endometrium	CL:0002255	74.98	gold quality
testis	UBERON:0000473	73.86	gold quality
right testis	UBERON:0004534	72.12	gold quality
left testis	UBERON:0004533	72.11	gold quality
lower esophagus mucosa	UBERON:0035834	71.85	gold quality
squamous epithelium	UBERON:0006914	71.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	11.28
E-ANND-3	yes	5.61
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

260 targeting IGF2BP3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-8068	99.98	73.85	2376
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Literature-anchored findings (GeneRIF, showing 40)

• The growth regulating gene IMP-3 has been characterized as a candidate for Silver-Russell syndrome. (PMID:12161597)
• KOC is a sensitive and specific marker for carcinomas and high-grade dysplastic lesions of the pancreatic ductal epithelium (PMID:15644775)
• IMP-3 knock down by RNA interference significantly decreases levels of intracellular and secreted insulin-like growth factor-II (IGF-II) without affecting IGF-II leader-3, leader-4, c-myc, or beta-actin mRNA levels and H19 RNA levels. (PMID:15753088)
• We conclude that in patients with Barrett’s esophagus, GOAGE for IGF-II is found frequently in the metaplastic esophageal epithelium as well as in normal gastric and duodenal epithelia. (PMID:16339295)
• Adenocarcinoma in situ of the uterine cervix demonstrate significant expression of IMP3. (PMID:17192788)
• VICKZ exhibits differential expression in lymphoma subtypes and thus may be a marker of potential value in the diagnosis and study of hematopoietic neoplasia. (PMID:17296566)
• study shows KOC is highly expressed in high-grade lung neuroendocrine carcinomas but not low- & intermediate-grade carcinoid tumors, indicating KOC may play an important role in regulation of biologic behavior of high-grade lung neuroendocrine carcinomas (PMID:17316760)
• Immunohistochemical detection of KOC expression may be a useful diagnostic tool for distinguishing between small cell carcinoma and carcinoid tumor. (PMID:17521698)
• Data show that TTK protein kinase, lymphocyte antigen 6 complex locus K and insulin-like growth factor (IGF)-II mRNA binding protein 3 are tumor-associated antigens recognized by cytotoxic T lymphocytes and HLA-A24-restricted epitope peptides. (PMID:17784873)
• Expression of IMP3 and p53 may be helpful biomarkers in the distinction of endometrial serous carcinoma from endometrioid adenocarcinoma (PMID:17885673)
• IMP-3 appears to be involved in the progression of malignant melanoma (PMID:18204432)
• IMP3 may be a useful diagnostic marker in the assessment of endometrial cancers and their precursor lesions. (PMID:18223334)
• IMP3 over expression was associated with metastatic progression and death for patients with clear cell renal cell carcinoma (PMID:18260086)
• Rab27A acts as a novel mediator of invasion and metastasis promotion in human breast cancer cells through regulating the secretion of IGF-II. (PMID:18337447)
• IMP3 is an independent prognostic marker that can identify a group of patients with a high potential to develop progression. (PMID:18347170)
• IMP3 is a promising new marker with high specificity and sensitivity for pancreatic adenocarcinoma. (PMID:18499984)
• The concurrent use of KOC and S100A4 protein improves the diagnostic sensitivity of biliary brushings cytology. (PMID:18618724)
• IMP3 plays an important role in tumor invasion and metastasis and is a strong prognostic factor for patients with hepatocellular carcinoma. (PMID:18802962)
• We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high-grade neuroendocrine carcinomas. (PMID:18835627)
• IMP3 is a highly sensitive and specific biomarker for the diagnosis of invasive esophageal adenocarcinoma and high-grade dysplasia. (PMID:19047899)
• IGF2BP3 is the first biomarker of prognostic significance in ovarian clear cell carcinoma that has been validated in an independent case series. (PMID:19136932)
• IMP3 expression was correlated with tumor metastasis in osteosarcoma. (PMID:19192721)
• Diffuse IMP3 protein expression correlates with invasion and aggressiveness during cancer growth and metastasis in colorectal adenocarcinoma. (PMID:19357927)
• Results suggest that IMP3 plays important roles in the tumorigenesis, progress and prognosis of osteosarcoma, and the expression of IMP3 may be an important feature of osteosarcoma. (PMID:19426599)
• IMP3 could play a critical role in diagnosis of non-small cell lung cancer, identifying high-risk patients who might benefit from early and tailored systemic therapy. (PMID:19427669)
• IMP3 has the potential to be diagnostically useful in differentiating malignant and benign follicular pattern thyroid lesions. (PMID:19449140)
• IMP3 is an independent prognostic biomarker in bile duct carcinoma. (PMID:19467694)
• IMP3 is expressed in a subpopulation of ovarian cancer and a marker of good prognosis. (PMID:19620937)
• Increased IMP3 levels are associated with colon cancer progression and pathogenesis. (PMID:19672661)
• IMP3 is a novel biomarker for triple negative (basal-like) invasive mammary carcinoma (PMID:19695680)
• although IMP-3 expression is seemingly restricted to physiologic germinal center B cells, its expression in lymphomas of germinal center B origin is less robust (PMID:19698973)
• IMP-3 expression in melanoma vs nevus. A malignant circumstance, such as non-desmoplastic melanoma or atypical Spitz tumor, can be inferred when IMP-3 is expressed, suggesting potential diagnostic value of IMP-3 in melanocytic lesions. (PMID:19788446)
• insulin-like growth factor II mRNA binding protein 3 expression may be associated with an aggressive biological behavior. (PMID:20004948)
• Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) may have a role in progression of pancreatic ductal adenocarcinoma (PMID:20178612)
• The findings of focal S100P and/or IMP3 expression with reciprocal loss of pVHL in a few benign biopsies suggest a use of these markers in the detection of early epithelial dysplasia. (PMID:20382408)
• IMP3 immunoexpression and the IMP3+/PTEN+ pattern are the best independent and combination markers, respectively, to predict uterine serous carcinomas. (PMID:20472848)
• Expression of IMP3 appears to be an adverse prognostic factor for poorly differentiated thyroid carcinoma (PMID:20562850)
• High IMP3 is associated with prostate cancer. (PMID:20591150)
• IGF2BP3 genotype, haplotype and genetic model studies in metabolic syndrome traits and diabetes (PMID:20627640)
• IGF2BP3 might be a marker of disease aggressiveness in BCR/ABL1-positive ALL as consistently increasing levels of this transcript during follow-up predicted eventual leukemia relapse by three months (PMID:21414819)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	igf2bp3	ENSDARG00000010266
mus_musculus	Igf2bp3	ENSMUSG00000029814
rattus_norvegicus	Igf2bp3	ENSRNOG00000009052
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00010908
caenorhabditis_elegans		WBGENE00013347
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

Insulin-like growth factor 2 mRNA-binding protein 3 — O00425 (reviewed: O00425)

Alternative names: IGF-II mRNA-binding protein 3, KH domain-containing protein overexpressed in cancer, VICKZ family member 3

All UniProt accessions (2): O00425, F8WD15

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript ‘caging’ into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability. Binds to the 3’-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD. Binds to the 5’-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.

Subunit / interactions. Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Interacts with IGF2BP1. Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1.

Subcellular location. Nucleus. Cytoplasm. P-body. Stress granule.

Tissue specificity. Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines.

Domain organisation. All KH domains contribute to binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute. The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains does not seem to be required for localization to stress granules.

Miscellaneous. Autoantibodies against IGF2BP3 are detected in sera from some patients with a variety of carcinomas.

Similarity. Belongs to the RRM IMP/VICKZ family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00425-1	1	yes
O00425-2	2

RefSeq proteins (1): NP_006538* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013, PF00076

UniProt features (51 total): strand 15, helix 15, domain 6, mutagenesis site 4, modified residue 2, cross-link 2, sequence conflict 2, chain 1, splice variant 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6FQ1	X-RAY DIFFRACTION	1.31
6GX6	X-RAY DIFFRACTION	2
6FQR	X-RAY DIFFRACTION	2.1
6GQE	X-RAY DIFFRACTION	2.15
2E44	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00425-F1	77.71	0.29

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): 528, 450, 475, 184

Mutagenesis-validated functional residues (4):

Position	Phenotype
213	partial reduction in interaction with m6a-modified mrna; when associated with e-294. loss of homo- and heterooligomeriza
294	partial reduction in interaction with m6a-modified mrna; when associated with e-213. loss of homo- and heterooligomeriza
423–424	loss of interaction with m6a-modified mrna; when associated with 505-e-e-506. loss of homo- and heterooligomerization wi
505–506	loss of interaction with m6a-modified mrna; when associated with 422-e-e-423. loss of homo- and heterooligomerization wi

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-428359	Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA

MSigDB gene sets: 555 (showing top): MODULE_52, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ACTACCT_MIR196A_MIR196B, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, MODULE_151, TTTGTAG_MIR520D, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, VETTER_TARGETS_OF_PRKCA_AND_ETS1_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION

GO Biological Process (8): regulation of cytokine production (GO:0001817), translation (GO:0006412), nervous system development (GO:0007399), anatomical structure morphogenesis (GO:0009653), negative regulation of translation (GO:0017148), mRNA transport (GO:0051028), CRD-mediated mRNA stabilization (GO:0070934), regulation of translation (GO:0006417)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), translation regulator activity (GO:0045182), mRNA 5’-UTR binding (GO:0048027), N6-methyladenosine-containing RNA reader activity (GO:1990247), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
regulation of translation	2
mRNA binding	2
binding	2
cytoplasmic ribonucleoprotein granule	2
cellular anatomical structure	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
system development	1
developmental process	1
anatomical structure development	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
RNA transport	1
mRNA stabilization	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
molecular_function	1
RNA binding	1
protein-RNA adaptor activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGF2BP3	IGF2	P01344	989
IGF2BP3	YTHDF1	Q9BYJ9	906
IGF2BP3	ELAVL1	Q15717	860
IGF2BP3	YTHDF3	Q7Z739	850
IGF2BP3	YTHDC1	Q96MU7	849
IGF2BP3	YTHDF2	Q9Y5A9	845
IGF2BP3	F5H6H0	F5H6H0	842
IGF2BP3	YTHDC2	Q9H6S0	836
IGF2BP3	METTL3	Q86U44	836
IGF2BP3	METTL14	Q9HCE5	829
IGF2BP3	HNRNPA2B1	P22626	802
IGF2BP3	VIRMA	Q69YN4	797
IGF2BP3	FTO	Q9C0B1	794
IGF2BP3	HNRNPC	P07910	791
IGF2BP3	RBMX	P38159	765

IntAct

260 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
IGF2BP3	PCBP1	psi-mi:“MI:0915”(physical association)	0.560
IGF2BP3	TARDBP	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
YBX1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
FMR1	ACOT7	psi-mi:“MI:0914”(association)	0.500
DYRK1A	IGF2BP3	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (727): IGF2BP3 (Two-hybrid), PIH1D2 (Two-hybrid), IGF2BP3 (Affinity Capture-RNA), IGF2BP3 (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), G3BP2 (Co-fractionation), IGF2BP3 (Co-fractionation), IGF2BP3 (Co-fractionation), IGF2BP3 (Co-fractionation), IGF2BP3 (Co-fractionation), RAB2A (Co-fractionation), RPL37A (Co-fractionation), IGF2BP3 (Affinity Capture-MS)

ESM2 similar proteins: A2Y0J7, A8X6H1, B6HJ92, B8AM21, G5EB89, O00425, O22922, O42254, O57526, O62621, O73932, O74968, O76360, O88477, O95758, P17225, P24785, P26368, P26369, P26599, P40567, P43332, P45429, P90727, Q00438, Q03042, Q08CK7, Q0DKM4, Q10MR0, Q24562, Q29099, Q39244, Q54J05, Q5ZLP8, Q5ZLR4, Q62189, Q66H20, Q6ICX4, Q7LL14, Q8BHD7

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O00425, O19048, P38151, P51513, P57721, P57722, P57723, P57724, P60335, Q0VCU0, Q15365, Q15366, Q21920, Q2PFW9, Q5E9A3, Q5ZLP8, Q61990, Q80WA4, Q9CPN8, Q9JKN6, Q9SR13, Q9UNW9, O42254, O57526, O73932, O88477, Q08CK7, Q5RB68, Q5SF07, Q80VL1, Q8CGX0, Q9NZI8, Q9PW80, Q9Y6M1, A6ZKR5, B3LNH0, C5DIR2, C7GND0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
Formation of the ternary complex, and subsequently, the 43S complex	7	11.7×	1e-04
Translation initiation complex formation	7	10.3×	2e-04
Ribosomal scanning and start codon recognition	7	10.3×	2e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	11	10.0×	2e-06
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	12	9.1×	2e-06
Nonsense-Mediated Decay (NMD)	5	9.0×	5e-03
mRNA Polyadenylation	13	8.8×	2e-06
PTEN Regulation	5	8.8×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	6	35.2×	4e-06
centriole replication	5	21.7×	4e-04
stress granule assembly	5	17.8×	6e-04
negative regulation of translation	12	13.9×	6e-08
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	13.8×	2e-03
mRNA stabilization	6	13.0×	6e-04
translational initiation	6	12.7×	6e-04
mRNA export from nucleus	7	12.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3789 predictions. Top by Δscore:

Variant	Effect	Δscore
7:23312770:C:CT	donor_gain	1.0000
7:23312844:TTCAC:T	acceptor_gain	1.0000
7:23312845:TCAC:T	acceptor_gain	1.0000
7:23312846:CAC:C	acceptor_gain	1.0000
7:23312846:CACC:C	acceptor_gain	1.0000
7:23312847:AC:A	acceptor_gain	1.0000
7:23312847:ACC:A	acceptor_loss	1.0000
7:23312848:CC:C	acceptor_gain	1.0000
7:23312848:CCT:C	acceptor_loss	1.0000
7:23312849:C:CA	acceptor_loss	1.0000
7:23312849:C:CC	acceptor_gain	1.0000
7:23313531:T:TA	donor_gain	1.0000
7:23313649:TGAGC:T	acceptor_gain	1.0000
7:23313652:GC:G	acceptor_gain	1.0000
7:23313653:CC:C	acceptor_gain	1.0000
7:23313654:C:CC	acceptor_gain	1.0000
7:23317637:A:AC	donor_gain	1.0000
7:23317638:C:CC	donor_gain	1.0000
7:23317638:CCTTG:C	donor_loss	1.0000
7:23317710:CAAT:C	acceptor_gain	1.0000
7:23317711:AATC:A	acceptor_loss	1.0000
7:23317712:AT:A	acceptor_gain	1.0000
7:23317712:ATC:A	acceptor_loss	1.0000
7:23317713:TCT:T	acceptor_loss	1.0000
7:23317714:C:CC	acceptor_gain	1.0000
7:23317714:C:CG	acceptor_loss	1.0000
7:23317715:T:G	acceptor_loss	1.0000
7:23319258:T:TC	acceptor_gain	1.0000
7:23343716:A:AC	donor_gain	1.0000
7:23343717:C:CC	donor_gain	1.0000

AlphaMissense

3768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:23312444:A:C	I553S	1.000
7:23312456:G:T	A549D	1.000
7:23312755:C:G	G541R	1.000
7:23312760:A:C	I539R	1.000
7:23312760:A:T	I539K	1.000
7:23312766:A:T	V537D	1.000
7:23312808:A:T	V523D	1.000
7:23312814:A:T	V521D	1.000
7:23312821:C:G	A519P	1.000
7:23312835:T:G	Q514P	1.000
7:23312838:A:G	L513P	1.000
7:23313529:C:A	G507V	1.000
7:23313529:C:T	G507D	1.000
7:23313530:C:A	G507C	1.000
7:23313530:C:G	G507R	1.000
7:23313538:C:A	G504V	1.000
7:23313538:C:G	G504A	1.000
7:23313538:C:T	G504E	1.000
7:23313539:C:G	G504R	1.000
7:23313539:C:T	G504R	1.000
7:23313541:A:C	I503S	1.000
7:23313541:A:T	I503N	1.000
7:23313544:A:T	V502D	1.000
7:23313550:C:T	G500D	1.000
7:23313551:C:A	G500C	1.000
7:23313551:C:G	G500R	1.000
7:23313553:G:T	A499D	1.000
7:23313652:G:T	A466D	1.000
7:23317661:C:T	G458E	1.000
7:23317662:C:G	G458R	1.000

dbSNP variants (sampled 300 via entrez): RS1000007268 (7:23388557 G>A), RS1000010726 (7:23445745 A>T), RS1000030100 (7:23333419 C>A,T), RS1000035542 (7:23314729 T>C), RS1000037459 (7:23425637 T>A,C), RS1000085431 (7:23360208 T>C), RS1000125528 (7:23359096 C>A), RS1000127672 (7:23415105 G>A,C), RS1000130312 (7:23464667 G>A), RS1000144813 (7:23325159 A>G,T), RS1000152660 (7:23404949 G>A), RS1000164930 (7:23342628 G>A), RS1000184695 (7:23453659 T>C), RS1000197742 (7:23465122 T>C), RS1000198486 (7:23450149 CTG>C)

Disease associations

OMIM: gene MIM:608259 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000817_81	Height	2.000000e-14
GCST001956_34	Height	5.000000e-10
GCST002111_6	Personality dimensions	5.000000e-06
GCST002646_12	Infant length	8.000000e-08
GCST002647_65	Height	4.000000e-26
GCST004067_10	Hip circumference adjusted for BMI	2.000000e-08
GCST004067_206	Hip circumference adjusted for BMI	1.000000e-08
GCST005146_24	Birth weight	1.000000e-09
GCST008163_3	Height	4.000000e-06
GCST008362_167	Birth weight	9.000000e-15
GCST008363_57	Offspring birth weight	8.000000e-09
GCST009379_65	Type 2 diabetes	3.000000e-06
GCST009379_66	Type 2 diabetes	5.000000e-08
GCST011624_2	Tau burden	4.000000e-08
GCST012227_107	Hip circumference adjusted for BMI	2.000000e-09
GCST012227_108	Hip circumference adjusted for BMI	6.000000e-13
GCST90000025_330	Appendicular lean mass	2.000000e-47
GCST90002407_544	White blood cell count	3.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0006785	infant body height
EFO:0008039	BMI-adjusted hip circumference
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004760	t-tau measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067149 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.72	Kd	1924	nM	CHEMBL5653589
5.72	ED50	1924	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148577: Binding affinity to human IGF2BP3 incubated for 45 mins by Kinobead based pull down assay	kd	1.9241	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
bisphenol F	affects cotreatment, decreases methylation, increases expression, decreases expression	3
bisphenol A	decreases methylation, decreases expression, affects methylation, affects cotreatment	3
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression	2
bisphenol S	affects methylation, affects cotreatment, decreases expression	2
Arsenic	decreases expression, increases expression, affects reaction	2
Tobacco Smoke Pollution	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
tetrahydropalmatine	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651619	Binding	Binding affinity to human IGF2BP3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

11 cell lines: 10 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8I3	Abcam HCT 116 IGF2BP3 KO	Cancer cell line	Male
CVCL_B9KC	Abcam A-549 IGF2BP3 KO	Cancer cell line	Male
CVCL_D2FS	Abcam MCF-7 IGF2BP3 KO	Cancer cell line	Female
CVCL_D8DP	Ubigene ACHN IGF2BP3 KO	Cancer cell line	Male
CVCL_D8MX	Ubigene HCT 116 IGF2BP3 KO	Cancer cell line	Male
CVCL_D9GT	Ubigene HEK293 IGF2BP3 KO	Transformed cell line	Female
CVCL_F1Q9	HyCyte Hep-G2 KO-hIGF2BP3	Cancer cell line	Male
CVCL_SS32	HAP1 IGF2BP3 (-) 1	Cancer cell line	Male
CVCL_SS33	HAP1 IGF2BP3 (-) 2	Cancer cell line	Male
CVCL_XP74	HAP1 IGF2BP3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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