IGF2BP1

Summary

IGF2BP1 (insulin like growth factor 2 mRNA binding protein 1, HGNC:28866) is a protein-coding gene on chromosome 17q21.32, encoding Insulin-like growth factor 2 mRNA-binding protein 1 (Q9NZI8). RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs).

This gene encodes a member of the insulin-like growth factor 2 mRNA-binding protein family. The protein encoded by this gene contains four K homology domains and two RNA recognition motifs. It functions by binding to the mRNAs of certain genes, including insulin-like growth factor 2, beta-actin and beta-transducin repeat-containing protein, and regulating their translation. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10642 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• MANE Select transcript: NM_006546

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28866
Approved symbol	IGF2BP1
Name	insulin like growth factor 2 mRNA binding protein 1
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	IMP-1, IMP1
Ensembl gene	ENSG00000159217
Ensembl biotype	protein_coding
OMIM	608288
Entrez	10642

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000290341, ENST00000431824, ENST00000499130, ENST00000505562, ENST00000510023, ENST00000515586, ENST00000925689, ENST00000925690, ENST00000925691, ENST00000925692, ENST00000925693, ENST00000925694

RefSeq mRNA: 2 — MANE Select: NM_006546 NM_001160423, NM_006546

CCDS: CCDS11543, CCDS54138

Canonical transcript exons

ENST00000290341 — 15 exons

Exon	Start	End
ENSE00001044079	49038168	49038449
ENSE00001157684	49046260	49046373
ENSE00001157695	49044991	49045065
ENSE00001157701	49043967	49044086
ENSE00001157704	49043428	49043550
ENSE00001157710	49042242	49042377
ENSE00001157711	49041378	49041500
ENSE00001157717	49039957	49040091
ENSE00001218472	49049352	49056145
ENSE00001218478	48997385	48997920
ENSE00001642472	49045890	49046021
ENSE00003522199	48999109	48999169
ENSE00003546926	49025618	49025666
ENSE00003610403	49026466	49026517
ENSE00003627691	49031910	49031973

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 84.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.5421 / max 490.9757, expressed in 1086 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161502	24.5937	1008
161498	3.6367	474
161501	2.7863	542
161500	2.3642	378
161499	0.6363	240
161504	0.5467	131
161503	0.4378	259
161511	0.3006	171
161505	0.1430	53
161508	0.0516	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	84.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.67	gold quality
embryo	UBERON:0000922	82.83	gold quality
ganglionic eminence	UBERON:0004023	82.83	gold quality
adrenal tissue	UBERON:0018303	82.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.33	gold quality
ventricular zone	UBERON:0003053	80.96	gold quality
stromal cell of endometrium	CL:0002255	79.63	gold quality
buccal mucosa cell	CL:0002336	76.70	silver quality
cortical plate	UBERON:0005343	76.51	gold quality
nasal cavity epithelium	UBERON:0005384	72.16	gold quality
upper arm skin	UBERON:0004263	70.03	gold quality
heart right ventricle	UBERON:0002080	69.87	gold quality
testis	UBERON:0000473	69.28	gold quality
right testis	UBERON:0004534	68.82	gold quality
left testis	UBERON:0004533	67.96	gold quality
placenta	UBERON:0001987	67.34	gold quality
secondary oocyte	CL:0000655	66.48	gold quality
cerebellar vermis	UBERON:0004720	65.66	gold quality
pigmented layer of retina	UBERON:0001782	64.49	gold quality
parotid gland	UBERON:0001831	64.31	gold quality
kidney	UBERON:0002113	61.64	gold quality
adult mammalian kidney	UBERON:0000082	61.63	gold quality
layer of synovial tissue	UBERON:0007616	61.44	gold quality
postcentral gyrus	UBERON:0002581	60.99	gold quality
deltoid	UBERON:0001476	60.31	gold quality
parietal lobe	UBERON:0001872	59.85	gold quality
pancreatic ductal cell	CL:0002079	59.26	silver quality
cortex of kidney	UBERON:0001225	59.10	gold quality
esophagus squamous epithelium	UBERON:0006920	59.05	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	11.00
E-GEOD-93593	yes	7.22
E-CURD-112	yes	6.54
E-ANND-3	yes	5.69
E-MTAB-7381	no	50.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, HIF1A, MYC

miRNA regulators (miRDB)

236 targeting IGF2BP1, 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-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
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-4650-5P	99.98	64.69	999
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117

Literature-anchored findings (GeneRIF, showing 40)

• IMP1 localization is associated with motility and the major functions of IMP1 are carried out by the phylogenetically conserved KH domains (PMID:11973350)
• Aberrant CRD-BP expression may interfere with c-myc regulation. Copy number gains at 8q24 (c-myc), were seen in 48.3% of tumors, gains at 17q21 (CRD-BP) in 18.3%,& CRD-BP was seen in 58.5%, implying mechanisms of activation other than gene amplification. (PMID:12532419)
• IMP1 translocates to the nucleus and contains nuclear export signals within the RNA-binding KH2 and KH4 domains. (PMID:12921532)
• IMP-1 may have a role in progression of ovarian cancer (PMID:14767552)
• Intestinal epithelial cells continue to express IMP1 postnatally, and Imp1(-/-) mice exhibited impaired development of the intestine, with small and misshapen villi and twisted colon crypts. (PMID:15121863)
• highest frequency of CRD-BP positive tumors was observed in meningiomas (PMID:15159028)
• intimate association of fragile X mental retardation protein and IMP1 suggests a link between mRNA transport and translational repression in mammalian cells (PMID:15282548)
• A cooperative mechanism for the binding of IMP-1 to RNA. (PMID:15314207)
• CRD-BP has a dominant role in proliferation of human K562 cells by an IGF-II-dependent mechanism independent of its ability to serve as a c-myc mRNA masking protein (PMID:15355996)
• normal role for CRD-BP/IMP1 in pluripotent stem cells with high renewal capacity (PMID:15769738)
• We have further characterized the interaction between PABP and IMP1 with the 3’ end of the adenine-rich autoregulatory sequence (PMID:17212783)
• IMP-1 expression is likely to play important roles in lung cancer development and progression (PMID:17255263)
• Study isolated the IMP1-containing RNP granules and found that they represent a unique ribonucleoprotein entity distinct from neuronal hStaufen and/or fragile X mental retardation protein granules, processing bodies, and stress granules. (PMID:17289661)
• 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)
• IMP1 is an oncogenic factor that is involved in promoting elevated proliferation by stabilizing the c-myc mRNA in ovarian carcinoma cells. (PMID:17546046)
• IMP-1 associates with Gag protein of HIV-1 and its overexpression affects virus assembly. (PMID:18385235)
• Knockdown of CRD-BP inhibits NF-kappaB activity, induces apoptosis, and suppresses proliferation and tumorigenic properties of melanoma cells. (PMID:18454174)
• These experiments suggest that in breast cancer cells, the expression of ZBP1 and the expression of beta-catenin are coordinately regulated. (PMID:18490442)
• IGFBP-1, which can inhibit IGF action, also increased during in-vitro decidualization of cultured human ESCs. (PMID:19038974)
• These data suggest that repression of ZBP1 by blocking beta-catenin binding at the ZBP1 promoter deregulates its associated mRNAs, leading to the phenotypic changes of breast cancers. (PMID:19461076)
• IGF2BP1, by binding to the HCV 5’UTR and/or HCV 3’UTR, recruits eIF3 and enhances HCV IRES-mediated translation. (PMID:19541769)
• CRD-BP prevents degradation of betaTrCP1 mRNA by attenuating its miR-183-dependent interaction with Ago2. (PMID:19647520)
• expression of 8S-LOX and 15S-LOX-2 suppresses CRD-BP/IMP-1 expression, resulting in inhibition of human prostate carcinoma PC-3 cell proliferation. (PMID:19661680)
• IMP1 interacts with HIV1 Rev protein and its ectopic expression causes relocation of Rev from the nucleus to the cytoplasm and ectopic expression of IMP1 leads to significant accumulation of multiple spliced HIV-1 RNA. (PMID:19726068)
• Wnt/beta-catenin signaling induces expression of an RNA-binding protein, CRD-BP, which in turn binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. (PMID:19887615)
• IGF2BP1 genotype, haplotype and genetic model studies in metabolic syndrome traits and diabetes (PMID:20627640)
• IMP1 plays a role in regulating the packaging of MLV genomic RNA and can be used for improving production of retroviral vectors (PMID:21209918)
• Studies identify a novel proapoptotic gene target, CYFIP2, which is downregulated by IMP-1, and mediates the regulation of cell survival and K-Ras expression in colon cancer cells. (PMID:21252116)
• Data show that the let-7 (let-7d and let-7g) target IMP-1 stabilizes the mRNA of MDR1. (PMID:21618519)
• sh-RNA knockdown of CRD-BP enhances the effect of dacarbazine, temozolomide, vinblastine, & etoposide on both primary and metastatic melanoma cell lines. (PMID:21981993)
• these data indicate that ZBP1 may function as an adapter to export the Ro/Y3 RNA complex from nuclei. (PMID:22114317)
• The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1. (PMID:22125086)
• The data of this study suggest that RNA-binding proteins can be used as a tool to identify the post-transcriptional regulation of gene expression in the establishment and function of neural circuits involved in addiction behaviors. (PMID:22240322)
• in both T47D and MDA231 human breast carcinoma cells IMP1/ZBP1 functions to suppress cell invasion (PMID:22266909)
• IGF2BP1 promotes the velocity and directionality of tumor-derived cell migration by determining the cytoplasmic fate of two novel target mRNAs: MAPK4 and PTEN (PMID:22279049)
• IGF2BP1 is a potent oncogenic factor that regulates the adhesion, migration and invasiveness of tumor cells by modulating intracellular signaling. (PMID:22983196)
• Shows role for CRD-BP in the regulation of melanoma cell invasion and highlights the importance of the hypoxic microenvironment in determining cell fate. (PMID:23038779)
• IGF2BP1 acts as an adaptor protein that recruits the CCR4-NOT complex and thereby initiates the degradation of the lncRNA HULC. (PMID:23728852)
• our study suggests that IMP1might play an important role in the progression of choriocarcinoma through the regulation of cell migration and invasion. (PMID:23911878)
• The RNA-binding protein IGF2BP1 is an important protumorigenic factor in liver carcinogenesis. (PMID:24395596)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Igf2bp1	ENSMUSG00000013415
rattus_norvegicus	Igf2bp1	ENSRNOG00000006122
drosophila_melanogaster	Psi	FBGN0014870
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00007534
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), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

Insulin-like growth factor 2 mRNA-binding protein 1 — Q9NZI8 (reviewed: Q9NZI8)

Alternative names: Coding region determinant-binding protein, IGF-II mRNA-binding protein 1, VICKZ family member 1, Zipcode-binding protein 1

All UniProt accessions (1): Q9NZI8

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding factor that recruits 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. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons. Regulates localized beta-actin/ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves a conserved 54-nucleotide element in the ACTB mRNA 3’-UTR, known as the ‘zipcode’. The RNP thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, prevents ACTB mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. Monomeric ACTB then assembles into the subcortical actin cytoskeleton. During neuronal development, key regulator of neurite outgrowth, growth cone guidance and neuronal cell migration, presumably through the spatiotemporal fine tuning of protein synthesis, such as that of ACTB. May regulate mRNA transport to activated synapses. Binds to and stabilizes ABCB1/MDR-1 mRNA. During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing. Binds to the 3’-UTR of IGF2 mRNA by a mechanism of cooperative and sequential dimerization and regulates IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA, in the coding region instability determinant (CRD) of the open reading frame (ORF), hence preventing MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD. Binding to MYC mRNA is enhanced by m6A-modification of the CRD. Binds to the 3’-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to the oncofetal H19 transcript and to the neuron-specific TAU mRNA and regulates their localizations. Binds to and stabilizes BTRC/FBW1A mRNA. Binds to the adenine-rich autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent interaction with AGO2. Promotes the directed movement of tumor-derived cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3’-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization. Interacts with Hepatitis C virus (HCV) 5’-UTR and 3’-UTR and specifically enhances translation at the HCV IRES, but not 5’-cap-dependent translation, possibly by recruiting eIF3. Interacts with HIV-1 GAG protein and blocks the formation of infectious HIV-1 particles. Reduces HIV-1 assembly by inhibiting viral RNA packaging, as well as assembly and processing of GAG protein on cellular membranes. During cellular stress, such as oxidative stress or heat shock, stabilizes target mRNAs that are recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts.

Subunit / interactions. Can form homodimers and heterodimers with IGF2BP1 and IGF2BP3. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. During HCV infection, identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon. Interacts (via the KH domains) with HIV-1 GAG (via the second zinc finger motif of NC). Associates (via the RRM domains and KH domains) with HIV-1 particles. Identified in a mRNP complex, composed of at least DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with DHX9, ELAVL2, HNRNPA2B1, HNRNPC, HNRNPH1, HNRNPU, IGF2BP2, ILF2, and YBX1. Interacts with FMR1. Component of a multisubunit autoregulatory RNP complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1/UNR. Directly interacts with PABPC1. Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Interacts with ELAVL4 in an RNA-dependent manner. Associates with microtubules and polysomes. Interacts with AGO1 and AGO2. Interacts with ELAVL1 and MATR3. Interacts (via KH3 and KH4 domains) with SEPIN14P20 peptide RBRP; the interaction results in increased binding of IGF2BP1 to N6-methyladenosine (m6A)-containing mRNAs.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region. P-body. Stress granule. Cell projection. Lamellipodium. Dendrite. Dendritic spine. Growth cone. Filopodium. Axon.

Tissue specificity. Mainly expressed in the embryo, including in fetal liver, fetal lung, fetal kidney, fetal thymus (at protein level). Also expressed follicles of ovary, as well as in gonocytes of testis, spermatogonia, semen, oocytes and placenta (at protein level). Expressed in various cancers, including testis and lung cancers (at protein level), as well as kidney, prostate and trachea cancers.

Post-translational modifications. Phosphorylated at Ser-181 by mTORC2 cotranslationally, promoting binding to the 3’-UTR of IGF2 mRNA.

Domain organisation. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full-length protein. The 4 KH domains are important to suppress HIV-1 infectivity.

Induction. May be up-regulated in response to CTNNB1/beta-catenin activation.

Similarity. Belongs to the RRM IMP/VICKZ family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZI8-1	1	yes
Q9NZI8-2	2

RefSeq proteins (2): NP_001153895, NP_006537* (*=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
IPR034837	IGF2BP1_RRM1	Domain
IPR034842	IGF2BP1_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013, PF00076

UniProt features (58 total): helix 19, strand 12, mutagenesis site 7, domain 6, modified residue 4, sequence conflict 4, region of interest 3, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6QEY	X-RAY DIFFRACTION	2.2
3KRM	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZI8-F1	77.90	0.25

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): 12, 73, 181, 528

Mutagenesis-validated functional residues (7):

Position	Phenotype
213–214	50-fold decrease in rna-binding affinity, decreased location in cytoplasmic rnp, increased nuclear location; when associ
213	partial reduction in interaction with m6a-modified mrna; when associated with e-294.
294–295	50-fold decrease in rna-binding affinity, decreased location in cytoplasmic rnp, increased nuclear location; when associ
294	partial reduction in interaction with m6a-modified mrna; when associated with e-213.
423–424	loss of binding to rbpr and loss of interaction with m6a-modified mrna; when associated with 505-e-e-506.
423–424	50-fold decrease in rna-binding affinity, decreased location in cytoplasmic rnp, increased nuclear location; when associ
505–506	loss of binding to rbpr and loss of interaction with m6a-modified mrna; when associated with 423-e-e-424.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-428359	Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA
R-HSA-5687128	MAPK6/MAPK4 signaling

MSigDB gene sets: 329 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, ACTACCT_MIR196A_MIR196B, MYOGENIN_Q6, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GAANYNYGACNY_UNKNOWN, TGCACTT_MIR519C_MIR519B_MIR519A, AAGCCAT_MIR135A_MIR135B, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AREB6_01, GOBP_NEUROGENESIS, KONG_E2F3_TARGETS, ACTGCAG_MIR173P, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (15): regulation of cytokine production (GO:0001817), nervous system development (GO:0007399), regulation of mRNA stability involved in response to stress (GO:0010610), negative regulation of translation (GO:0017148), pallium cell proliferation in forebrain (GO:0022013), mRNA transport (GO:0051028), regulation of stress granule assembly (GO:0062028), CRD-mediated mRNA stabilization (GO:0070934), neuronal stem cell population maintenance (GO:0097150), dendrite arborization (GO:0140059), negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900152), positive regulation of cytoplasmic translation (GO:2000767), RNA localization (GO:0006403), regulation of translation (GO:0006417), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (8): RNA binding (GO:0003723), mRNA binding (GO:0003729), 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 (18): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), lamellipodium (GO:0030027), filopodium (GO:0030175), growth cone (GO:0030426), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), perinuclear region of cytoplasm (GO:0048471), CRD-mediated mRNA stability complex (GO:0070937), ribonucleoprotein complex (GO:1990904), axon (GO:0030424), dendrite (GO:0030425), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of RNA	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
translation	2
regulation of translation	2
RNA binding	2
mRNA binding	2
binding	2
cytoplasmic ribonucleoprotein granule	2
cytoplasm	2
neuron projection	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
system development	1
response to stress	1
cellular response to stress	1
regulation of mRNA stability	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
pallium development	1
cell proliferation in forebrain	1
RNA transport	1
stress granule assembly	1
regulation of organelle assembly	1
mRNA stabilization	1
stem cell population maintenance	1
dendrite morphogenesis	1
neuron projection arborization	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
negative regulation of mRNA catabolic process	1
cytoplasmic translation	1
positive regulation of translation	1
regulation of cytoplasmic translation	1
macromolecule localization	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
nucleic acid binding	1

Protein interactions and networks

STRING

2218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGF2BP1	IGF2	P01344	992
IGF2BP1	MYC	P01106	980
IGF2BP1	ACTB	P02570	967
IGF2BP1	ELAVL1	Q15717	943
IGF2BP1	YTHDF1	Q9BYJ9	932
IGF2BP1	YTHDC1	Q96MU7	907
IGF2BP1	HNRNPA2B1	P22626	894
IGF2BP1	BTRC	Q9Y297	892
IGF2BP1	MATR3	P43243	875
IGF2BP1	HNRNPC	P07910	873
IGF2BP1	YTHDC2	Q9H6S0	860
IGF2BP1	YTHDF2	Q9Y5A9	853
IGF2BP1	YTHDF3	Q7Z739	851
IGF2BP1	ALKBH5	Q6P6C2	849
IGF2BP1	VIRMA	Q69YN4	848

IntAct

241 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF2BP1	HNRNPU	psi-mi:“MI:0403”(colocalization)	0.680
IGF2BP1	YBX1	psi-mi:“MI:0403”(colocalization)	0.680
IGF2BP1	STAU1	psi-mi:“MI:0915”(physical association)	0.650
IGF2BP1	STAU1	psi-mi:“MI:0403”(colocalization)	0.650
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	SYNCRIP	psi-mi:“MI:0914”(association)	0.580
IGF2BP1	SYNCRIP	psi-mi:“MI:0403”(colocalization)	0.580
IGF2BP1	DHX9	psi-mi:“MI:0403”(colocalization)	0.580
IGF2BP1	ELAVL1	psi-mi:“MI:0403”(colocalization)	0.580
MOV10	IGF2BP1	psi-mi:“MI:0915”(physical association)	0.560
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
Cbx7	IGF2BP1	psi-mi:“MI:0915”(physical association)	0.500
FMR1	ACOT7	psi-mi:“MI:0914”(association)	0.500
IGF2BP1	DYRK1A	psi-mi:“MI:0915”(physical association)	0.500
DYRK1A	IGF2BP3	psi-mi:“MI:0914”(association)	0.500
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
SAMD4A	INPPL1	psi-mi:“MI:2364”(proximity)	0.480
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480

BioGRID (710): IGF2BP1 (Affinity Capture-RNA), IGF2BP1 (Affinity Capture-RNA), IGF2BP1 (Affinity Capture-MS), IGF2BP1 (Affinity Capture-MS), IGF2BP1 (Affinity Capture-MS), IGF2BP1 (Affinity Capture-MS), IGF2BP2 (Co-fractionation), IGF2BP3 (Co-fractionation), RAB2A (Co-fractionation), RPL37A (Co-fractionation), BIRC2 (Protein-RNA), IGF2BP1 (Affinity Capture-MS), IGF2BP1 (Affinity Capture-MS), IGF2BP1 (Affinity Capture-MS), IGF2BP1 (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: A0A1W2P872, O00425, O19048, O42254, O57526, O73932, O88477, P60335, Q08CK7, Q15365, Q5E9A3, Q5RB68, Q5SF07, Q5ZLP8, Q80VL1, Q8CGX0, Q9CPN8, Q9NZI8, Q9PW80, Q9UNW9, Q9Y6M1, A0A0B4KGY6, A6ZKR5, B3LNH0, C5DIR2, C7GND0, C8Z3W4, O75179, P38199, P57721, P57722, P57723, P57724, Q00341, Q0VCU0, Q15366, Q5R439, Q61990, Q8UVD9, Q96AE4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IGF2BP1	“up-regulates quantity”	ACTB	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 205 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
Loss of Nlp from mitotic centrosomes	7	7.7×	4e-03
Loss of proteins required for interphase microtubule organization from the centrosome	7	7.7×	4e-03
AURKA Activation by TPX2	7	7.3×	5e-03
mRNA Polyadenylation	12	7.3×	7e-05
Regulation of PLK1 Activity at G2/M Transition	8	7.0×	3e-03
Recruitment of mitotic centrosome proteins and complexes	7	6.6×	8e-03
Processing of Capped Intron-Containing Pre-mRNA	10	5.7×	3e-03
mRNA Splicing - Major Pathway	14	5.3×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	6	32.7×	1e-05
centriole replication	6	24.1×	3e-05
stress granule assembly	6	19.8×	9e-05
mRNA stabilization	8	16.1×	1e-05
intrinsic apoptotic signaling pathway	6	11.8×	1e-03
negative regulation of translation	10	10.8×	1e-05
regulation of alternative mRNA splicing, via spliceosome	8	10.7×	1e-04
translational initiation	5	9.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2859 predictions. Top by Δscore:

Variant	Effect	Δscore
17:49025662:GGGAA:G	donor_gain	1.0000
17:49025663:GGAA:G	donor_gain	1.0000
17:49025663:GGAAG:G	donor_gain	1.0000
17:49025664:G:GT	donor_gain	1.0000
17:49025664:G:T	donor_gain	1.0000
17:49025664:GAA:G	donor_gain	1.0000
17:49025667:G:GG	donor_gain	1.0000
17:49025667:GTAAG:G	donor_loss	1.0000
17:49025668:TAAG:T	donor_loss	1.0000
17:49026460:TCCTA:T	acceptor_loss	1.0000
17:49026461:CCTAG:C	acceptor_loss	1.0000
17:49026464:AGGTA:A	acceptor_loss	1.0000
17:49026518:G:T	donor_loss	1.0000
17:49026519:T:A	donor_loss	1.0000
17:49031908:A:AG	acceptor_gain	1.0000
17:49031909:G:GA	acceptor_gain	1.0000
17:49031970:GGCA:G	donor_gain	1.0000
17:49031971:GCA:G	donor_gain	1.0000
17:49031971:GCAG:G	donor_gain	1.0000
17:49031974:G:GG	donor_gain	1.0000
17:49031987:G:T	donor_gain	1.0000
17:49038450:G:GG	donor_gain	1.0000
17:49039947:T:TA	acceptor_gain	1.0000
17:49039948:G:A	acceptor_gain	1.0000
17:49039955:A:AG	acceptor_gain	1.0000
17:49039955:AG:A	acceptor_gain	1.0000
17:49039956:G:GG	acceptor_gain	1.0000
17:49039956:GG:G	acceptor_gain	1.0000
17:49039956:GGAT:G	acceptor_gain	1.0000
17:49039956:GGATA:G	acceptor_gain	1.0000

AlphaMissense

3796 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48997756:T:A	L4H	1.000
17:48997756:T:C	L4P	1.000
17:48997758:T:G	Y5D	1.000
17:48997864:C:A	A40D	1.000
17:48997866:T:C	F41L	1.000
17:48997867:T:C	F41S	1.000
17:48997867:T:G	F41C	1.000
17:48997868:C:A	F41L	1.000
17:48997868:C:G	F41L	1.000
17:48997902:G:C	A53P	1.000
17:48997903:C:A	A53D	1.000
17:49031943:T:A	V124D	1.000
17:49031948:T:G	Y126D	1.000
17:49038182:T:C	L139P	1.000
17:49038371:T:A	V202E	1.000
17:49038386:T:A	V207E	1.000
17:49038388:G:C	G208R	1.000
17:49038388:G:T	G208C	1.000
17:49038389:G:A	G208D	1.000
17:49038389:G:T	G208V	1.000
17:49038391:G:C	A209P	1.000
17:49038392:C:A	A209D	1.000
17:49038395:T:A	I210N	1.000
17:49038395:T:C	I210T	1.000
17:49038395:T:G	I210S	1.000
17:49038398:T:A	I211N	1.000
17:49038398:T:G	I211S	1.000
17:49038400:G:A	G212S	1.000
17:49038400:G:C	G212R	1.000
17:49038400:G:T	G212C	1.000

dbSNP variants (sampled 300 via entrez): RS1000008188 (17:49003313 A>G), RS1000039656 (17:49044603 T>G), RS1000116245 (17:48996643 G>A,T), RS1000158135 (17:49003300 G>A), RS1000187886 (17:49004361 T>C), RS1000190397 (17:48996412 C>G,T), RS1000304910 (17:49055151 A>C,G), RS1000379923 (17:49032007 G>A,C,T), RS1000443156 (17:49002896 G>A), RS1000490899 (17:49003599 A>G), RS1000523943 (17:49020063 GT>G), RS1000534069 (17:49019496 T>C), RS1000535398 (17:49039312 G>T), RS1000647240 (17:49053866 T>C), RS1000657008 (17:49053678 C>A,G)

Disease associations

OMIM: gene MIM:608288 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000609_1	Primary tooth development (time to first tooth eruption)	8.000000e-07
GCST000610_8	Primary tooth development (number of teeth)	2.000000e-08
GCST001942_17	Prostate cancer	2.000000e-09
GCST002030_10	Primary tooth development (time to first tooth eruption)	2.000000e-14
GCST002031_9	Primary tooth development (number of teeth)	7.000000e-16
GCST003435_27	Body fat percentage	2.000000e-08
GCST003435_7	Body fat percentage	3.000000e-08
GCST005316_214	Intelligence (MTAG)	7.000000e-09
GCST008258_19	Alcohol use disorder (consumption score)	2.000000e-08
GCST008258_5	Alcohol use disorder (consumption score)	6.000000e-09
GCST008757_29	Alcohol consumption	4.000000e-10
GCST010659_2	Waist circumference	2.000000e-07
GCST010703_257	Brain morphology (MOSTest)	1.000000e-13
GCST010988_62	Adult body size	6.000000e-17
GCST011122_25	Walking pace	6.000000e-10
GCST011743_65	HDL cholesterol levels in HIV infection	6.000000e-06
GCST90020028_1423	Hip circumference adjusted for BMI	4.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007800	body fat percentage
EFO:0004337	intelligence
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009458	alcohol use disorder measurement
EFO:0004346	neuroimaging measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465263 (SINGLE PROTEIN)

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

ChEMBL bioactivities

11 potent at pChembl≥5 of 14 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.54	Kd	2.88	nM	CHEMBL5399930
7.96	Kd	10.9	nM	CHEMBL5399930
7.75	Kd	17.69	nM	CHEMBL5653589
7.75	ED50	17.69	nM	CHEMBL5653589
7.18	Kd	66.2	nM	CHEMBL508185
6.94	Kd	115.3	nM	CHEMBL3752910
6.94	ED50	115.3	nM	CHEMBL3752910
6.08	Kd	840	nM	CHEMBL5557581
5.92	Kd	1200	nM	CHEMBL508185
5.85	Kd	1400	nM	CHEMBL5557581

PubChem BioAssay actives

9 with measured affinity, of 58 total; 5 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
[(2S,8S,9R,10R,13R,14S,16R,17R)-17-[(E,2R)-6-acetyloxy-2-hydroxy-6-methyl-3-oxohept-4-en-2-yl]-16-hydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-2-yl] 2-[4-(4-fluorophenyl)-5-oxo-1,2,4-triazol-1-yl]acetate	2014156: Binding affinity to His-tagged recombinant IGF2BP1 (unknown origin) assessed as dissociation constant by surface plasmon resonance assay	kd	0.0029	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148575: Binding affinity to human IGF2BP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0177	uM
[(E,6R)-6-[(2S,8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxohept-3-en-2-yl] acetate	2014156: Binding affinity to His-tagged recombinant IGF2BP1 (unknown origin) assessed as dissociation constant by surface plasmon resonance assay	kd	0.0662	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148575: Binding affinity to human IGF2BP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1153	uM
[4-(1,3-benzodioxol-5-yl)piperazin-1-yl]-[4-[[3-(hydroxymethyl)indol-1-yl]methyl]phenyl]methanone	2092119: Binding affinity to recombinant full-length human IGF2BP1 KH34 domain by MST assay	kd	0.8400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Cisplatin	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Particulate Matter	affects methylation, increases abundance, increases expression	2
mivebresib	affects response to substance, decreases expression	1
CPI-0610	decreases expression	1
INCB057643	decreases expression	1
ARV-771	decreases expression	1
dicrotophos	increases expression	1
quinone	decreases expression, decreases reaction, affects binding, increases reaction	1
methylmercuric chloride	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
K 7174	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5367889	Binding	Binding affinity to His-tagged recombinant IGF2BP1 (unknown origin) assessed as dissociation constant by surface plasmon resonance assay	Discovery of Triazolyl Derivatives of Cucurbitacin B Targeting IGF2BP1 against Non-Small Cell Lung Cancer. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8I1	Abcam HCT 116 IGF2BP1 KO	Cancer cell line	Male
CVCL_B9KA	Abcam A-549 IGF2BP1 KO	Cancer cell line	Male
CVCL_D2FR	Abcam MCF-7 IGF2BP1 KO	Cancer cell line	Female
CVCL_D7J5	Ubigene A-375 IGF2BP1 KO	Cancer cell line	Female
CVCL_D7RU	Ubigene A-549 IGF2BP1 KO	Cancer cell line	Male
CVCL_E6ZB	DEE ExIGF2BP1	Spontaneously immortalized cell line	Sex unspecified

Clinical trials (associated diseases)

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