IGF2BP2

Summary

IGF2BP2 (insulin like growth factor 2 mRNA binding protein 2, HGNC:28867) is a protein-coding gene on chromosome 3q27.2, encoding Insulin-like growth factor 2 mRNA-binding protein 2 (Q9Y6M1). RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs).

This gene encodes a protein that binds the 5’ UTR of insulin-like growth factor 2 (IGF2) mRNA and regulates its translation. It plays an important role in metabolism and variation in this gene is associated with susceptibility to diabetes. Alternative splicing and promoter usage results in multiple transcript variants. Related pseudogenes are found on several chromosomes.

Source: NCBI Gene 10644 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diabetes mellitus, noninsulin-dependent (No Known Disease Relationship, GenCC)
• GWAS associations: 89
• Clinical variants (ClinVar): 67 total — 1 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_006548

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28867
Approved symbol	IGF2BP2
Name	insulin like growth factor 2 mRNA binding protein 2
Location	3q27.2
Locus type	gene with protein product
Status	Approved
Aliases	IMP-2, p62, P62
Ensembl gene	ENSG00000073792
Ensembl biotype	protein_coding
OMIM	608289
Entrez	10644

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 22 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000346192, ENST00000382199, ENST00000421047, ENST00000457616, ENST00000461957, ENST00000464166, ENST00000466214, ENST00000466476, ENST00000493302, ENST00000494906, ENST00000496495, ENST00000881588, ENST00000881589, ENST00000881590, ENST00000881591, ENST00000921325, ENST00000921326, ENST00000921327, ENST00000921328, ENST00000921329, ENST00000921330, ENST00000921331, ENST00000921332, ENST00000921333, ENST00000921334, ENST00000921335, ENST00000921336, ENST00000921337, ENST00000955762

RefSeq mRNA: 7 — MANE Select: NM_006548 NM_001007225, NM_001291869, NM_001291872, NM_001291873, NM_001291874, NM_001291875, NM_006548

CCDS: CCDS3273, CCDS33903, CCDS77869, CCDS77870

Canonical transcript exons

ENST00000382199 — 16 exons

Exon	Start	End
ENSE00001029224	185689355	185689627
ENSE00001029236	185647025	185647138
ENSE00001235323	185672541	185672669
ENSE00001863328	185643130	185645623
ENSE00001952994	185824783	185825042
ENSE00003557901	185652094	185652168
ENSE00003590909	185696612	185696663
ENSE00003608375	185675791	185675913
ENSE00003611785	185658341	185658409
ENSE00003612774	185823153	185823213
ENSE00003622778	185687057	185687191
ENSE00003634603	185675296	185675431
ENSE00003638401	185649403	185649534
ENSE00003638741	185657286	185657402
ENSE00003641365	185692699	185692762
ENSE00003644347	185698299	185698347

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7460 / max 147.3777, expressed in 1500 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45937	6.0131	1296
45938	5.3672	1350
45934	1.3548	463
45939	0.9341	461
45935	0.0592	18
45932	0.0154	3
45931	0.0023	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.72	gold quality
adrenal tissue	UBERON:0018303	97.32	gold quality
ventricular zone	UBERON:0003053	95.42	gold quality
sural nerve	UBERON:0015488	94.95	gold quality
stromal cell of endometrium	CL:0002255	94.35	gold quality
embryo	UBERON:0000922	94.16	gold quality
ganglionic eminence	UBERON:0004023	93.68	gold quality
amniotic fluid	UBERON:0000173	92.61	gold quality
bronchial epithelial cell	CL:0002328	92.14	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.09	gold quality
cartilage tissue	UBERON:0002418	91.88	gold quality
cortical plate	UBERON:0005343	90.82	gold quality
right uterine tube	UBERON:0001302	90.79	gold quality
epithelium of bronchus	UBERON:0002031	90.31	gold quality
bronchus	UBERON:0002185	89.98	gold quality
rectum	UBERON:0001052	89.92	gold quality
pigmented layer of retina	UBERON:0001782	89.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.75	gold quality
colonic mucosa	UBERON:0000317	88.42	gold quality
secondary oocyte	CL:0000655	88.41	gold quality
pylorus	UBERON:0001166	87.87	gold quality
placenta	UBERON:0001987	87.65	gold quality
monocyte	CL:0000576	87.07	gold quality
mononuclear cell	CL:0000842	86.76	gold quality
duodenum	UBERON:0002114	86.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.45	gold quality
tibial nerve	UBERON:0001323	86.34	gold quality
gall bladder	UBERON:0002110	86.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.11	gold quality
leukocyte	CL:0000738	85.74	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	8.38
E-ANND-3	yes	8.29
E-MTAB-10885	no	345.49
E-MTAB-10290	no	124.39
E-GEOD-124858	no	48.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HMGA2, NFKB1, NFKB, RELA

miRNA regulators (miRDB)

156 targeting IGF2BP2, 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-4262	100.00	73.26	3931
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
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-23B-5P	99.98	66.07	587
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 40)

• HMGA2 differentially regulates expression of IMP family members during mouse embryogenesis. (PMID:15225648)
• Study suggests that there is a significant association between expression of IMP-2 and the growth of tumor cells, in which IMP-2 is associated with apoptosis induced by tretinoin. (PMID:15618018)
• 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)
• we provide evidence that there is a strong and statistically significant correlation between HMGA2 and IMP2 gene expression in human liposarcomas. (PMID:17426251)
• The association of 6 loci with type 2 diabetes risk in Japanese patients is reported. (PMID:18162508)
• Novel evidence for a rare variant in the 3’ downstream region of IGF2BP2 in type 2 diabetes in French Caucasians. (PMID:18430866)
• Little evidence of association was observed between SNPs in IGF2BP2 and type 2 diabetes in African Americans. (PMID:18443202)
• Data confirmed the associations of single nucleotide polymorphisms in IGF2BP2 with risk for type 2 diabetes in Asians. (PMID:18469204)
• Gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population. (PMID:18597214)
• IGF2BP2 SNPs revealed a significant association with type 2 diabetes (PMID:18598350)
• Variants of CDKAL1 and IGF2BP2 attenuate the first phase of glucose-stimulated insulin secretion but show no effect on the second phase of insulin secretion in hyperglycmia and type 2 diabetes. (PMID:18618095)
• The results indicate that in Chinese Hans, common variants in IGF2BP2 loci independently or additively contribute to type 2 diabetes risk, likely mediated through beta-cell dysfunction. (PMID:18633108)
• Study show that polymorphisms in IGF2BP2 were associated with type 2 diabetes risk in the studied population. (PMID:18694974)
• Data show that SNPs in IGF2BP2 did not confer a significant risk for type 2 diabetes in Pima Indians. (PMID:19008344)
• IGF2BP2 stimulation increases radiosensitivity of a pancreatic cancer cell line through endoplasmic reticulum stress under hypoxic comditions. (PMID:19018773)
• Type 2 diabetes susceptibility of IGF2BP2 was confirmed in Japanese. (PMID:19033397)
• IGF2BP2 single-nucleotide polymorphisms are associated with body fat and this effect on body fat influences insulin resistance which may contribute to type 2 diabetes mellitus risk. (PMID:19148120)
• The IGF2BP2 variant shows a nominal interaction with exposure to famine in wartime in utero and predisposition to type 2 diabetes. (PMID:19258437)
• prostate cancer was inversely associated with the IGF2BP2 rs4402960 T allele (PMID:20142250)
• findings show that IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of type 2 diabetes and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patientsmellitus (PMID:20523342)
• non-replications of IGF2BP2 associations with type 2 diabetes (PMID:20627640)
• Data reveal how the posttranscriptional regulation of gene expression by IMP-2 contributes to the control of adhesion structures and stable microtubules and demonstrate an important function for IMP-2 in cellular motility. (PMID:20956565)
• The induction of a steatotic phenotype implies that p62 plays a role in hepatic pathophysiology (PMID:21145819)
• IGF2 is emerging as an important gene for ovarian cancer. (PMID:21422097)
• Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 5’ untranslated region, and the translational initiation of this mRNA (PMID:21576258)
• involved in the selective autophagic clearance of non-ubiquitylated aggregation-prone substrates (PMID:21771882)
• meta-analysis suggested that IGF2BP2 rs4402960 polymorphism conferred elevated risk of T2DM, especially in European, East Asian and South Asian populations (PMID:21839790)
• rs4402960 and rs1470579 lymorphisms of the IFG2BP2po is a risk factor for developing type 2 diabetes. (PMID:22015911)
• IGF2BP2 genetic variation is associated with type 2 diabetes. (PMID:22032244)
• Six SNP(rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK)risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. (PMID:22096510)
• Data validate that IGF2BP2 susceptibility variants rs4402960 and rs1470579 associate with T2DM in Lebanese Arabs. (PMID:22245690)
• Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation. (PMID:22427968)
• genetic association studies: Data suggest that an SNP in IGF2BP2 (rs4402960) is associated with type 2 diabetes; IGF2BP2 may have genetic interactions with insulin-like growth factor II with a protective effect in male patients with type 1 diabetes. (PMID:22770937)
• oncofetal insulin-like growth factor 2 mRNA-binding protein 2 (IMP2, IGF2BP2) regulates oxidative phosphorylation (OXPHOS) in primary glioblastoma (GBM) sphere cultures (gliomaspheres) (PMID:22899010)
• Association to type 2 diabetes was found for rs13266634 (SLC30A8), rs7923837 (HHEX), rs10811661 (CDKN2A/2B), rs4402960 (IGF2BP2), rs12779790 (CDC123/CAMK1D), and rs2237892 (KCNQ1). (PMID:22923468)
• IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject. (PMID:23029108)
• In African Americans, seven of the 29 SNPs examined were found to be associated with T2D risk at P </= 0.05, including rs6769511 (IGF2BP2). (PMID:23144361)
• p62 exerts IGF2-independent antiapoptotic action, which is facilitated via phosphorylation of ERK1/2. (PMID:23257922)
• Polymorphisms in PPARgamma(2) and IGF2BP2 were shown to be highly correlated with GDM occurrence, whereas no correlation was found for KCNQ1 polymorphisms. (PMID:23364967)
• IGF2BP2 genetic variants contribute to insulin resistance in Russian NIDDM patients. (PMID:23403707)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	igf2bp2a	ENSDARG00000003421
danio_rerio	igf2bp2b	ENSDARG00000099758
mus_musculus	Igf2bp2	ENSMUSG00000033581
rattus_norvegicus	Igf2bp2	ENSRNOG00000025946
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): KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), 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 2 — Q9Y6M1 (reviewed: Q9Y6M1)

Alternative names: Hepatocellular carcinoma autoantigen p62, IGF-II mRNA-binding protein 2, VICKZ family member 2

All UniProt accessions (2): Q9Y6M1, F8W930

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. Binds to the 5’-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. 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.

Subunit / interactions. Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Interacts with HNRPD. Interacts with IGF2BP1. Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1. Interacts with the HOXB-AS3 peptide; the interaction increases MYC stability.

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

Tissue specificity. Expressed in oocytes, granulosa cells of small and growing follicles, Leydig cells, spermatogonia and semen (at protein level). Expressed in testicular cancer (at protein level). Expressed weakly in heart, placenta, skeletal muscle, bone marrow, colon, kidney, salivary glands, testis and pancreas. Detected in fetal liver, fetal ovary, gonocytes and interstitial cells of the testis.

Domain organisation. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. The contribution to RNA-binding of individual KH domains may be target-specific. 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.

Miscellaneous. Autoantibodies against IGF2BP2 are detected in sera from some patients with hepatocellular carcinoma. Generated by alternative initiation at Met-69.

Similarity. Belongs to the RRM IMP/VICKZ family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9Y6M1-2	1	yes
Q9Y6M1-1	2
Q9Y6M1-3	3
Q9Y6M1-4	4
Q9Y6M1-5	5
Q9Y6M1-6	6

RefSeq proteins (7): NP_001007226, NP_001278798, NP_001278801, NP_001278802, NP_001278803, NP_001278804, NP_006539* (*=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
IPR034843	IGF2BP2_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013, PF00076

UniProt features (46 total): helix 12, strand 11, domain 6, modified residue 5, splice variant 4, mutagenesis site 4, chain 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6ROL	X-RAY DIFFRACTION	2.1
7Q98	X-RAY DIFFRACTION	2.5
7Q99	X-RAY DIFFRACTION	2.55
2CQH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6M1-F1	77.70	0.32

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 (5): 162, 164, 550, 1, 11

Mutagenesis-validated functional residues (4):

Position	Phenotype
211	significantly impaired binding to actb transcript but little effect on myc transcript binding, accumulation in the nucle
292	significantly impaired binding to actb transcript but little effect on myc transcript binding, accumulation in the nucle
445–446	significantly impaired binding to actb and myc transcripts and loss of interaction with m6a-modified mrna; when associat
527–528	significantly impaired binding to actb and myc transcripts and loss of interaction with m6a-modified mrna; when associat

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: 275 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GCACCTT_MIR18A_MIR18B, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, CGGAARNGGCNG_UNKNOWN, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CACCAGC_MIR138, CCATCCA_MIR432, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY

GO Biological Process (12): regulation of cytokine production (GO:0001817), nervous system development (GO:0007399), anatomical structure morphogenesis (GO:0009653), negative regulation of translation (GO:0017148), RNA stabilization (GO:0043489), mRNA transport (GO:0051028), CRD-mediated mRNA stabilization (GO:0070934), energy homeostasis (GO:0097009), cold-induced thermogenesis (GO:0106106), regulation of translation (GO:0006417), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

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 (6): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), 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
system development	1
developmental process	1
anatomical structure development	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
regulation of RNA stability	1
negative regulation of RNA catabolic process	1
RNA transport	1
mRNA stabilization	1
multicellular organismal-level homeostasis	1
adaptive thermogenesis	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic 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
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGF2BP2	F5H6H0	F5H6H0	995
IGF2BP2	IGF2	P01344	994
IGF2BP2	FTO	Q9C0B1	914
IGF2BP2	HHEX	Q03014	908
IGF2BP2	CDKAL1	Q5VV42	898
IGF2BP2	YTHDC1	Q96MU7	876
IGF2BP2	DHX9	Q08211	867
IGF2BP2	SLC30A8	Q8IWU4	863
IGF2BP2	YTHDF1	Q9BYJ9	862
IGF2BP2	METTL3	Q86U44	855
IGF2BP2	YTHDC2	Q9H6S0	853
IGF2BP2	YTHDF3	Q7Z739	848
IGF2BP2	YTHDF2	Q9Y5A9	847
IGF2BP2	METTL14	Q9HCE5	831
IGF2BP2	HNRNPA2B1	P22626	826
IGF2BP2	HNRNPC	P07910	826

IntAct

240 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
TARDBP	IGF2BP2	psi-mi:“MI:0915”(physical association)	0.560
IGF2BP2	HNRNPD	psi-mi:“MI:0915”(physical association)	0.530
IGF2BP2	HNRNPD	psi-mi:“MI:0407”(direct interaction)	0.530
HNRNPD	IGF2BP2	psi-mi:“MI:0915”(physical association)	0.530
N	HNRNPDL	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
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MRPS34	ZZEF1	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
IGF2BP2	RBM3	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (508): IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Co-fractionation), IGF2BP2 (Proximity Label-MS), IGF2BP2 (Proximity Label-MS), IGF2BP2 (Proximity Label-MS), IGF2BP2 (Proximity Label-MS), IGF2BP2 (Proximity Label-MS), IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Proximity Label-MS), IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Affinity Capture-MS), IGF2BP2 (Affinity Capture-RNA)

ESM2 similar proteins: A6ZKR5, A7RP64, A7TT46, B3LNH0, B9W892, C5DIR2, C5E0I9, C7GND0, C8Z3W4, O00425, O42254, O57526, O59810, O73932, O74774, O74919, O88477, P06105, P10869, P31688, P38151, P38199, P91277, Q08CK7, Q29IG6, Q4PMC9, Q54K66, Q5F414, Q5RB68, Q5SF07, Q5ZLP8, Q6CNI6, Q6DDB9, Q6FUD8, Q6VBQ6, Q6VBQ8, Q6VEU3, Q756R8, Q7YRD0, Q8AVH4

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O19048, O19049, O73932, O74919, P51513, P57721, P57722, P60335, P61978, P61979, P61980, Q15365, Q15366, Q2PFW9, Q32PX7, Q3T0D0, Q4R4M6, Q5E9A3, Q5R5H8, Q5RB68, Q5SF07, Q5ZIQ3, Q5ZLP8, Q61990, Q80WA4, Q8UVD9, Q91WJ8, Q96AE4, Q96I24, Q9JKN6, Q9LZ82, Q9SZH4, Q9UNW9, Q9Y6M1, O00425, O42254, O57526, O88477

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MTOR	“up-regulates activity”	IGF2BP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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	10	13.1×	1e-06
Loss of proteins required for interphase microtubule organization from the centrosome	10	13.1×	1e-06
AURKA Activation by TPX2	10	12.6×	1e-06
Recruitment of mitotic centrosome proteins and complexes	10	11.2×	2e-06
Regulation of PLK1 Activity at G2/M Transition	10	10.5×	4e-06
Anchoring of the basal body to the plasma membrane	11	10.3×	1e-06
SUMOylation of RNA binding proteins	5	9.8×	6e-03
Degradation of DVL	5	9.8×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	5	29.9×	2e-04
centriole replication	5	22.1×	4e-04
translational initiation	6	13.0×	8e-04
mRNA transport	8	12.7×	1e-04
mRNA stabilization	5	11.0×	8e-03
positive regulation of translation	8	11.0×	2e-04
negative regulation of translation	8	9.4×	4e-04
RNA processing	6	7.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	58
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
144319	GRCh38/hg38 3q27.2(chr3:185506271-185977882)x1	Pathogenic

SpliceAI

3529 predictions. Top by Δscore:

Variant	Effect	Δscore
3:185647065:T:TA	donor_gain	1.0000
3:185647134:TTCAC:T	acceptor_gain	1.0000
3:185647135:TCAC:T	acceptor_gain	1.0000
3:185647136:CAC:C	acceptor_gain	1.0000
3:185647136:CACC:C	acceptor_gain	1.0000
3:185647137:AC:A	acceptor_gain	1.0000
3:185647138:CC:C	acceptor_gain	1.0000
3:185647139:C:CA	acceptor_loss	1.0000
3:185647139:C:CC	acceptor_gain	1.0000
3:185647140:T:A	acceptor_loss	1.0000
3:185647141:G:C	acceptor_gain	1.0000
3:185647141:G:GC	acceptor_gain	1.0000
3:185649401:A:AC	donor_gain	1.0000
3:185649401:ACGGT:A	donor_gain	1.0000
3:185649402:C:CC	donor_gain	1.0000
3:185649402:CGGT:C	donor_gain	1.0000
3:185649402:CGGTC:C	donor_gain	1.0000
3:185657280:CCTCA:C	donor_loss	1.0000
3:185657281:CTCAC:C	donor_loss	1.0000
3:185657282:TCACC:T	donor_loss	1.0000
3:185657283:CA:C	donor_loss	1.0000
3:185657284:ACC:A	donor_loss	1.0000
3:185657399:GATA:G	acceptor_gain	1.0000
3:185657400:ATA:A	acceptor_gain	1.0000
3:185657401:TA:T	acceptor_gain	1.0000
3:185657402:AC:A	acceptor_loss	1.0000
3:185657403:C:CA	acceptor_loss	1.0000
3:185657403:C:CC	acceptor_gain	1.0000
3:185657412:C:CT	acceptor_gain	1.0000
3:185675289:GACTT:G	donor_loss	1.0000

AlphaMissense

3927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:185645607:A:C	I575S	1.000
3:185645607:A:G	I575T	1.000
3:185645607:A:T	I575N	1.000
3:185645613:C:G	R573P	1.000
3:185645616:T:G	Q572P	1.000
3:185645619:G:T	A571E	1.000
3:185645620:C:G	A571P	1.000
3:185647037:G:C	F565L	1.000
3:185647037:G:T	F565L	1.000
3:185647039:A:G	F565L	1.000
3:185647044:C:A	G563V	1.000
3:185647044:C:T	G563E	1.000
3:185647045:C:A	G563W	1.000
3:185647045:C:G	G563R	1.000
3:185647045:C:T	G563R	1.000
3:185647056:A:T	V559D	1.000
3:185647098:A:T	V545E	1.000
3:185647104:A:T	V543D	1.000
3:185647110:G:T	A541E	1.000
3:185647111:C:G	A541P	1.000
3:185647125:T:G	Q536P	1.000
3:185647128:A:G	L535P	1.000
3:185647137:A:T	V532E	1.000
3:185649410:C:A	G529V	1.000
3:185649410:C:T	G529D	1.000
3:185649411:C:A	G529C	1.000
3:185649411:C:G	G529R	1.000
3:185649419:C:A	G526V	1.000
3:185649419:C:G	G526A	1.000
3:185649419:C:T	G526D	1.000

dbSNP variants (sampled 300 via entrez): RS1000006223 (3:185740261 G>A,C), RS1000022172 (3:185820608 T>C), RS1000052071 (3:185650576 T>C), RS1000096400 (3:185727237 A>C), RS1000097101 (3:185707025 A>C), RS1000099932 (3:185791439 C>A), RS1000109006 (3:185748125 C>A,T), RS1000128645 (3:185813956 T>C), RS1000132929 (3:185771903 G>A), RS1000142570 (3:185784558 T>C), RS1000159113 (3:185697999 C>G,T), RS1000165023 (3:185776025 C>T), RS1000172352 (3:185694328 T>C), RS1000183050 (3:185700301 T>C), RS1000200741 (3:185735725 G>A)

Disease associations

OMIM: gene MIM:608289 | disease phenotypes: MIM:162000, MIM:603860, MIM:609886

GenCC curated gene-disease

Disease	Classification	Inheritance
diabetes mellitus, noninsulin-dependent	No Known Disease Relationship	Unknown

Mondo (2): familial juvenile hyperuricemic nephropathy type 1 (MONDO:0008073), (MONDO:0007455)

Orphanet (3): OBSOLETE: Familial juvenile hyperuricemic nephropathy type 1 (Orphanet:209886), Autosomal dominant tubulointerstitial kidney disease (Orphanet:34149), UMOD-related autosomal dominant tubulointerstitial kidney disease (Orphanet:88950)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000855	Insulin resistance
HP:0003584	Late onset
HP:0005978	Type II diabetes mellitus
HP:0031819	Increased waist to hip ratio

GWAS associations

89 associations (top):

Study	Trait	p-value
GCST000024_3	Type 2 diabetes	9.000000e-16
GCST000025_1	Type 2 diabetes	9.000000e-16
GCST000028_7	Type 2 diabetes	9.000000e-16
GCST000167_11	Type 2 diabetes	8.000000e-08
GCST000221_3	Type 2 diabetes	1.000000e-09
GCST000383_7	Type 2 diabetes	1.000000e-06
GCST000712_19	Type 2 diabetes	2.000000e-09
GCST000817_57	Height	2.000000e-14
GCST001070_1	Type 2 diabetes	1.000000e-07
GCST001375_2	Diabetes (gestational)	2.000000e-07
GCST001527_31	Fasting blood glucose (BMI interaction)	6.000000e-07
GCST001809_10	Type 2 diabetes	4.000000e-07
GCST001809_12	Type 2 diabetes	4.000000e-09
GCST001809_15	Type 2 diabetes	2.000000e-13
GCST001809_17	Type 2 diabetes	2.000000e-19
GCST001809_7	Type 2 diabetes	5.000000e-06
GCST002128_1	Type 2 diabetes	5.000000e-14
GCST002352_24	Type 2 diabetes	1.000000e-17
GCST002541_7	Menarche (age at onset)	1.000000e-16
GCST002647_97	Height	1.000000e-29
GCST002806_4	Type 2 diabetes	3.000000e-06
GCST003619_2	Type 2 diabetes	3.000000e-14
GCST004067_73	Hip circumference adjusted for BMI	4.000000e-08
GCST004487_3	Peak insulin response	5.000000e-06
GCST004575_8	Acute insulin response	8.000000e-06
GCST004603_263	Platelet count	7.000000e-10
GCST004607_268	Plateletcrit	1.000000e-13
GCST004894_155	Type 2 diabetes	8.000000e-12
GCST004894_28	Type 2 diabetes	4.000000e-14
GCST004894_46	Type 2 diabetes	1.000000e-45

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004703	age at menarche
EFO:0008039	BMI-adjusted hip circumference
EFO:0008000	peak insulin response measurement
EFO:0006831	acute insulin response measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004541	HbA1c measurement
EFO:0004468	glucose measurement
EFO:0009270	heel bone mineral density
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0009924	Drugs used in diabetes use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0010525	propionic acid measurement
EFO:0004530	triglyceride measurement
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563693	Glomerulocystic Kidney Disease with Hyperuricemia and Isosthenuria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066203 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1470579	Efficacy	3	repaglinide	Diabetes Mellitus;Type 2
rs4402960	Efficacy	3	repaglinide	Diabetes Mellitus;Type 2

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1470579	IGF2BP2	3	1.50	1	repaglinide
rs4402960	IGF2BP2	3	1.50	1	repaglinide
rs6769511	IGF2BP2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
sodium arsenate	decreases expression, increases abundance, increases expression	2
sodium arsenite	decreases expression, increases reaction, affects binding, decreases reaction	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Arsenic Trioxide	increases expression, increases secretion, increases stability, decreases expression, decreases reaction (+2 more)	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cisplatin	decreases expression, affects response to substance, affects reaction	2
Lead	affects methylation, affects splicing	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
chloropicrin	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5500674	Binding	Binding affinity to Histidine-tagged IMP-2 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	Targeting insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) for the treatment of cancer. — Eur J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8I2	Abcam HCT 116 IGF2BP2 KO	Cancer cell line	Male
CVCL_B8X7	Abcam MCF-7 IGF2BP2 KO	Cancer cell line	Female
CVCL_B9KB	Abcam A-549 IGF2BP2 KO	Cancer cell line	Male
CVCL_D7IY	Ubigene 786-O IGF2BP2 KO	Cancer cell line	Male
CVCL_D9GS	Ubigene HEK293 IGF2BP2 KO	Transformed cell line	Female
CVCL_D9WC	Ubigene HSC-3 IGF2BP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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