ILF2

Summary

ILF2 (interleukin enhancer binding factor 2, HGNC:6037) is a protein-coding gene on chromosome 1q21.3, encoding Interleukin enhancer-binding factor 2 (Q12905). Chromatin-interacting protein that forms a stable heterodimer with interleukin enhancer-binding factor 3/ILF3 and plays a role in several biological processes including transcription, innate immunity or cell growth. It is a common-essential gene (DepMap: required in 96.4% of cancer cell lines).

The protein encoded by this gene is a transcription factor required for T-cell expression of the interleukin 2 gene. It also binds RNA and is an essential component for encapsidation and protein priming of hepatitis B viral polymerase. The encoded 45 kDa protein (NF45, ILF2) forms a complex with the 90 kDa interleukin enhancer-binding factor 3 (NF90, ILF3), and this complex has been shown to affect the redistribution of nuclear mRNA to the cytoplasm, to repair DNA breaks by nonhomologous end joining, and to negatively regulate the microRNA processing pathway. Knockdown of NF45 or NF90 protein retards cell growth, possibly by inhibition of mRNA stabilization. Alternative splicing results in multiple transcript variants. Related pseudogenes have been found on chromosomes 3 and 14.

Source: NCBI Gene 3608 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_004515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6037
Approved symbol	ILF2
Name	interleukin enhancer binding factor 2
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	NF45
Ensembl gene	ENSG00000143621
Ensembl biotype	protein_coding
OMIM	603181
Entrez	3608

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361891, ENST00000368681, ENST00000368684, ENST00000480213, ENST00000615950, ENST00000903915, ENST00000903916, ENST00000903917, ENST00000903918, ENST00000911663, ENST00000911664, ENST00000911665, ENST00000911666, ENST00000911667, ENST00000911668, ENST00000911669, ENST00000911670, ENST00000911671, ENST00000962112

RefSeq mRNA: 2 — MANE Select: NM_004515 NM_001267809, NM_004515

CCDS: CCDS1050, CCDS72919

Canonical transcript exons

ENST00000361891 — 14 exons

Exon	Start	End
ENSE00000961204	153663215	153663276
ENSE00000961205	153663019	153663133
ENSE00001175619	153665220	153665336
ENSE00001175625	153667555	153667657
ENSE00001175629	153668000	153668077
ENSE00001175633	153668453	153668557
ENSE00001257280	153670171	153670230
ENSE00001447747	153670918	153670993
ENSE00003498939	153669836	153669878
ENSE00003508468	153664043	153664130
ENSE00003598732	153662705	153662795
ENSE00003620546	153664396	153664474
ENSE00003719532	153661788	153662556
ENSE00003786221	153665663	153665728

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 124.5440 / max 1067.0636, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14714	112.6139	1826
14713	11.9301	1763

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.16	gold quality
embryo	UBERON:0000922	99.03	gold quality
ventricular zone	UBERON:0003053	98.99	gold quality
cortical plate	UBERON:0005343	98.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.50	gold quality
right testis	UBERON:0004534	98.38	gold quality
left testis	UBERON:0004533	98.33	gold quality
islet of Langerhans	UBERON:0000006	98.31	gold quality
adenohypophysis	UBERON:0002196	97.81	gold quality
metanephros cortex	UBERON:0010533	97.72	gold quality
rectum	UBERON:0001052	97.70	gold quality
mucosa of transverse colon	UBERON:0004991	97.70	gold quality
body of pancreas	UBERON:0001150	97.69	gold quality
endometrium epithelium	UBERON:0004811	97.65	gold quality
skin of abdomen	UBERON:0001416	97.55	gold quality
testis	UBERON:0000473	97.54	gold quality
left lobe of thyroid gland	UBERON:0001120	97.47	gold quality
left uterine tube	UBERON:0001303	97.44	gold quality
right lobe of thyroid gland	UBERON:0001119	97.43	gold quality
right adrenal gland	UBERON:0001233	97.33	gold quality
right adrenal gland cortex	UBERON:0035827	97.28	gold quality
skin of leg	UBERON:0001511	97.27	gold quality
minor salivary gland	UBERON:0001830	97.22	gold quality
upper lobe of left lung	UBERON:0008952	97.21	gold quality
left adrenal gland	UBERON:0001234	97.20	gold quality
body of stomach	UBERON:0001161	97.17	gold quality
esophagus mucosa	UBERON:0002469	97.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.16	gold quality
left adrenal gland cortex	UBERON:0035825	97.15	gold quality
pituitary gland	UBERON:0000007	97.13	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	40.94
E-HCAD-10	yes	35.53
E-MTAB-9067	yes	23.23
E-HCAD-13	yes	19.71
E-MTAB-10553	yes	6.99
E-CURD-97	no	2912.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
ACRV1	Activation
IL2	Unknown
ILF3	Unknown

miRNA regulators (miRDB)

47 targeting ILF2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-496	98.66	69.80	931
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 38)

• plays important role in protein priming of HBV polymerase (PMID:11958450)
• NF45 is a is a highly conserved transcriptional activator of the gene IL-2. (PMID:15817156)
• Cell growth is retarded and giant multinucleated cells accumulate when the expression of NF45 or NF90, but not NF110, is reduced in HeLa cells. (PMID:18458058)
• Results suggest that the association of the NF90-NF45 complex with pri-miRNAs impairs access of the Microprocessor complex to the pri-miRNAs, resulting in a reduction of mature miRNA production. (PMID:19398578)
• The data presented are consistent with a model in which translation of cIAP1 is governed, at least in part, by NF45, a novel cellular IRES trans-acting factor. (PMID:19893574)
• our results identify NF45 and NF90 as novel regulators of HS4-dependent human IL13 transcription in response to T cell activation (PMID:20051514)
• ILF2 recruits a DNA-associated replication and transcription complex, of which it is a part, to its target DNA sequence. (PMID:20808282)
• spatial interactions of hnRNPH1, NF45, and C14orf166 with HCVc174 likely modulate HCV or cellular functions during acute and chronic HCV infection (PMID:21823664)
• The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining (PMID:21969602)
• AU-rich 5’ UTRs harboring internal ribosome entry sites are regulated by NF45. NF45 regulates XIAP protein levels through interaction with its IRES. (PMID:23129811)
• These results suggest a novel molecular mechanism for the modulation of RNA granule assembly and disassembly by NFAR2, NF45, and phosphorylation at double-stranded RNA-activated kinase PKR sites. (PMID:24920670)
• These findings indicate that NF45 plays an important role in the growth regulation of glioma cells (PMID:25023405)
• These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression. (PMID:25286760)
• Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis (PMID:26059795)
• NF45 and NF90 are novel higher-eukaryote-specific factors required for the maturation of 60S ribosomal subunits. (PMID:26240280)
• NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma. (PMID:26276310)
• The RNA binding complexes NF45-NF90 and NF45-NF110 associate dynamically with the c-fos gene and function as transcriptional coactivators. (PMID:26381409)
• Deletion of the RNA binding domains of NF45 and NF90 diminished the enhancement of HIV infection and gene expression. (PMID:26891316)
• NF90-NF45 stimulates an elevation of EGF receptor levels via the suppression of miR-7 biogenesis, resulting in the promotion of cell proliferation in Hepatocellular Carcinoma. (PMID:27519414)
• The data suggest that features of both the N- and C-termini of NF90 participate in the heterodimerization with NF45 and that the formation of NF90-NF45 changes the conformation of NF90’s RNA-binding motifs to a status in which the co-operative interplay of the RNA-binding motifs is optimal. (PMID:28062840)
• ILF2 interacts with RNA-binding proteins involved in the DNA damage response. (PMID:28669490)
• High expression of ILF2 was tightly correlated with lymph node metastasis, pathological stage and poor clinical prognosis in gastric cancer. (PMID:28831206)
• this study identifies a new role of ILF2 in the regulation of the NLRP3 inflammasome. (PMID:29655789)
• Overexpression studies revealed that NF-45 promoted cell growth and invasion and upregulated Rac1/Tiam1 signalling via 14-3-3epsilon protein in esophageal squamous cell carcinoma cell lines (PMID:30550728)
• Taken together, these results suggest that DANCR acts as a prognostic biomarker and increases HIF-1alpha mRNA stability by interacting with NF90/NF45, leading to metastasis and disease progression of nasopharyngeal carcinoma. (PMID:30555573)
• NF45 and NF90/NF110 operate as chromatin regulators of the immediate early response. (PMID:31022259)
• These results suggest that ILF2 may act as a potential antiviral agent against Japanese encephalitis virus infection. (PMID:31212927)
• Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects. (PMID:31878072)
• Circular RNA 406961 interacts with ILF2 to regulate PM2.5-induced inflammatory responses in human bronchial epithelial cells via activation of STAT3/JNK pathways. (PMID:32388272)
• NF45 and NF90 Regulate Mitotic Gene Expression by Competing with Staufen-Mediated mRNA Decay. (PMID:32433969)
• Deletion of interleukin enhancer binding factor 2 (ILF2) resulted in defective biliary development and bile flow blockage. (PMID:32709532)
• Interleukin Enhancer Binding Factor 2 Regulates Cell Viability and Apoptosis of Human Brain Vascular Smooth Muscle Cells. (PMID:32748330)
• Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2. (PMID:33009960)
• CRNDE-h transcript/miR-136-5p axis regulates interleukin enhancer binding factor 2 expression to promote hepatocellular carcinoma cell proliferation. (PMID:34153299)
• ILF2 enhances the DNA cytosine deaminase activity of tumor mutator APOBEC3B in multiple myeloma cells. (PMID:35145187)
• Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2). (PMID:35333683)
• NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer. (PMID:37047232)
• Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer. (PMID:38622522)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ilf2	ENSDARG00000014591
mus_musculus	Ilf2	ENSMUSG00000001016
rattus_norvegicus	Ilf2	ENSRNOG00000014154
drosophila_melanogaster	CG5641	FBGN0038046
caenorhabditis_elegans		WBGENE00011253

Paralogs (14): STAU2 (ENSG00000040341), ZFR (ENSG00000056097), ADAT1 (ENSG00000065457), ZFR2 (ENSG00000105278), STAU1 (ENSG00000124214), ILF3 (ENSG00000129351), TARBP2 (ENSG00000139546), ADAD2 (ENSG00000140955), ADAR (ENSG00000160710), ADAD1 (ENSG00000164113), STRBP (ENSG00000165209), PRKRA (ENSG00000180228), ADARB2 (ENSG00000185736), ADARB1 (ENSG00000197381)

Protein

Protein identifiers

Interleukin enhancer-binding factor 2 — Q12905 (reviewed: Q12905)

Alternative names: Nuclear factor of activated T-cells 45 kDa

All UniProt accessions (5): Q12905, A0A0A0MRL0, B4DY09, F4ZW62, X6R6Z1

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin-interacting protein that forms a stable heterodimer with interleukin enhancer-binding factor 3/ILF3 and plays a role in several biological processes including transcription, innate immunity or cell growth. Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. Together with ILF3, forms an RNA-binding complex that is required for mitotic progression and cytokinesis by regulating the expression of a cluster of mitotic genes. Mechanistically, competes with STAU1/STAU2-mediated mRNA decay. Also plays a role in the inhibition of various viruses including Japanese encephalitis virus or enterovirus 71. (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3.

Subunit / interactions. Forms heterodimers with ILF3. ILF2-ILF3 heterodimers may also bind to PRKDC/XRCC7: this may stabilize the interaction of PRKDC/XRCC7 and the heterodimeric complex of G22P1/KU70 and XRCC5/KU80. Forms a complex with ILF3, YLPM1, KHDRBS1, RBMX, NCOA5 and PPP1CA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with IGF2BP1. Interacts with CRBN; this interaction promotes ubiquitination and subsequent degradation of ILF2. (Microbial infection) Interacts with Japanese encephalitis virus protein NS3. (Microbial infection) Interacts with enterovirus 71 protein 2B; this interaction relocalizes ILF2 from the nucleus to the cytoplasm.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Post-translational modifications. Ubiquitinated at Lys-45 by CRBN with polyubiquitin chains by the CUL4-RING E3 ligase (CRL4-CRBN) and then degraded by the proteasome.

RefSeq proteins (2): NP_001254738, NP_004506* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006561	DZF_dom	Domain
IPR043519	NT_sf	Homologous_superfamily
IPR049401	DZF_dom_N	Domain
IPR049402	DZF_dom_C	Domain
IPR052134	ILF2	Family

Pfam: PF07528, PF20965

UniProt features (17 total): modified residue 6, cross-link 3, compositionally biased region 3, region of interest 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12905-F1	89.79	0.85

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 (9): 52, 68, 388, 45, 186, 364, 16, 16, 24

Mutagenesis-validated functional residues (1):

Position	Phenotype
45	completely abolishes the effect of crbn on ilf2.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9833482	PKR-mediated signaling

MSigDB gene sets: 281 (showing top): MORF_MTA1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GCM_NPM1, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_RAD21, MORF_CDK2, MORF_HDAC2, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, MORF_TERF1, GCM_PSME1

GO Biological Process (1): positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): DNA binding (GO:0003677), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), membrane (GO:0016020), specific granule lumen (GO:0035580), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813), ribonucleoprotein complex (GO:1990904), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nucleic acid binding	2
nuclear lumen	2
intracellular organelle lumen	2
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
RNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
secretory granule lumen	1
specific granule	1
tertiary granule	1
ficolin-1-rich granule	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3024 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ILF2	ILF3	Q12906	988
ILF2	DHX9	Q08211	901
ILF2	HNRNPM	P52272	887
ILF2	HNRNPH1	P31943	860
ILF2	HNRNPH2	P55795	841
ILF2	HNRNPC	P07910	822
ILF2	MATR3	P43243	796
ILF2	DDX5	P17844	761
ILF2	YBX1	P16990	734
ILF2	EIF2AK2	P19525	688
ILF2	HNRNPF	P52597	662
ILF2	FUS	P35637	643
ILF2	TOP2B	Q02880	625
ILF2	XRCC6	P12956	613
ILF2	KHSRP	Q92945	610

IntAct

336 interactions, top by confidence:

A	B	Type	Score
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
FUS	HNRNPA1	psi-mi:“MI:0914”(association)	0.670
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ILF2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	ILF2	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	ILF2	psi-mi:“MI:0915”(physical association)	0.560
IQGAP1	ILF2	psi-mi:“MI:0915”(physical association)	0.560
ILF2	PICK1	psi-mi:“MI:0915”(physical association)	0.560
INCA1	ILF2	psi-mi:“MI:0915”(physical association)	0.560
ILF2	ZMYND12	psi-mi:“MI:0915”(physical association)	0.560
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
ILF2	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
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
	ILF2	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (862): ILF2 (Affinity Capture-MS), ILF2 (Two-hybrid), CCNDBP1 (Two-hybrid), ILF2 (Affinity Capture-MS), ILF2 (Affinity Capture-MS), ILF2 (Affinity Capture-MS), ILF2 (Affinity Capture-MS), ILF2 (Affinity Capture-MS), ILF2 (Affinity Capture-MS), ILF2 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), EP300 (Affinity Capture-MS), PRKDC (Affinity Capture-MS), MCM2 (Affinity Capture-MS), MCM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0TYJ0, A2AWA9, A7MB28, F1QH17, O55047, O70133, O88506, O88532, P14401, Q08CW1, Q08E27, Q12905, Q12959, Q13330, Q1ECX4, Q4V860, Q5PYH5, Q5R6Y5, Q5RA95, Q5RAN1, Q5RB16, Q5REX3, Q5RFJ1, Q5ZIL4, Q62599, Q62696, Q68FK8, Q6AY57, Q6AYR2, Q6DCD0, Q6GL57, Q6NZ06, Q6NZH6, Q6P8G1, Q6ZVM7, Q80W47, Q811D0, Q8K4B0, Q8K4Q0, Q8N122

Diamond homologs: B8GAM6, O88532, P51400, P78563, P97616, Q08E27, Q12905, Q12906, Q562A2, Q5R6Y5, Q5REX3, Q5RFJ1, Q5U231, Q5ZIL4, Q6DCD0, Q6DD04, Q6GL57, Q6GPM1, Q6NXA4, Q6NZ06, Q6P8G1, Q6PCR6, Q7TP98, Q7ZW47, Q8CJ67, Q91550, Q91WM1, Q91ZS8, Q96KR1, Q96SI9, Q9CXY6, Q9JI20, Q9JIL3, Q9JKU6, Q9NII1, Q9NS39, Q9NUL3, Q9UPR6, Q9Z1X4, Q9VG73

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ILF2	“form complex”	NF90-NF45	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
mRNA Polyadenylation	14	8.7×	5e-07
Processing of Capped Intron-Containing Pre-mRNA	13	7.6×	6e-06
mRNA Splicing - Major Pathway	15	5.8×	1e-05
Dengue Virus-Host Interactions	14	4.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	5	22.4×	7e-04
mRNA stabilization	6	12.8×	1e-03
stem cell population maintenance	5	12.3×	5e-03
regulation of alternative mRNA splicing, via spliceosome	8	11.4×	2e-04
mitophagy	6	11.2×	2e-03
positive regulation of DNA repair	5	10.5×	7e-03
intrinsic apoptotic signaling pathway	5	10.5×	7e-03
autophagosome maturation	5	10.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1418 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153662552:AAGAT:A	acceptor_gain	1.0000
1:153662553:AGAT:A	acceptor_gain	1.0000
1:153662554:GAT:G	acceptor_gain	1.0000
1:153662555:AT:A	acceptor_gain	1.0000
1:153662555:ATC:A	acceptor_loss	1.0000
1:153662557:C:CC	acceptor_gain	1.0000
1:153662703:A:AC	donor_gain	1.0000
1:153662704:C:CC	donor_gain	1.0000
1:153662704:CAG:C	donor_gain	1.0000
1:153662719:T:A	donor_gain	1.0000
1:153663209:CTGTA:C	donor_loss	1.0000
1:153663210:TGTAC:T	donor_loss	1.0000
1:153663211:GTA:G	donor_loss	1.0000
1:153663212:TACCT:T	donor_loss	1.0000
1:153663213:ACCTG:A	donor_loss	1.0000
1:153663214:C:A	donor_loss	1.0000
1:153663272:TGGCC:T	acceptor_gain	1.0000
1:153663274:GCCCT:G	acceptor_loss	1.0000
1:153663275:CC:C	acceptor_gain	1.0000
1:153663275:CCCTG:C	acceptor_loss	1.0000
1:153663276:CC:C	acceptor_gain	1.0000
1:153663276:CCT:C	acceptor_loss	1.0000
1:153663277:C:CC	acceptor_gain	1.0000
1:153663277:CTGAA:C	acceptor_loss	1.0000
1:153663278:T:G	acceptor_loss	1.0000
1:153664038:CTT:C	donor_loss	1.0000
1:153664039:TTA:T	donor_loss	1.0000
1:153664040:TACT:T	donor_loss	1.0000
1:153664041:A:AC	donor_gain	1.0000
1:153664041:ACTAG:A	donor_loss	1.0000

AlphaMissense

2534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153662517:A:T	V351E	1.000
1:153662767:A:G	L317P	1.000
1:153662772:C:A	Q315H	1.000
1:153662772:C:G	Q315H	1.000
1:153662776:G:T	A314D	1.000
1:153662777:C:G	A314P	1.000
1:153662784:G:C	C311W	1.000
1:153662785:C:T	C311Y	1.000
1:153662794:T:A	D308V	1.000
1:153662795:C:G	D308H	1.000
1:153663020:T:G	Q307P	1.000
1:153663074:T:C	D289G	1.000
1:153663083:C:T	G286D	1.000
1:153663084:C:G	G286R	1.000
1:153663090:A:G	S284P	1.000
1:153663098:A:G	L281P	1.000
1:153663107:C:A	G278V	1.000
1:153663107:C:T	G278E	1.000
1:153663108:C:G	G278R	1.000
1:153663108:C:T	G278R	1.000
1:153663113:G:T	A276D	1.000
1:153663276:C:G	G249R	1.000
1:153664047:A:G	L247P	1.000
1:153664060:A:G	W243R	1.000
1:153664060:A:T	W243R	1.000
1:153664422:C:A	W210C	1.000
1:153664422:C:G	W210C	1.000
1:153664424:A:G	W210R	1.000
1:153664424:A:T	W210R	1.000
1:153664430:C:G	A208P	1.000

dbSNP variants (sampled 300 via entrez): RS1000996435 (1:153669022 T>C), RS1001074206 (1:153661399 TCA>T), RS1001203403 (1:153661358 A>G), RS1001338250 (1:153661628 T>A,C,G), RS1001470536 (1:153667054 G>A), RS1001928971 (1:153671441 G>A), RS1002353332 (1:153668387 G>A), RS1002489110 (1:153668123 C>A,G,T), RS1002963035 (1:153662420 T>C,G), RS1003003979 (1:153665807 T>C), RS1003278680 (1:153662843 A>T), RS1003603317 (1:153670823 C>T), RS1003850372 (1:153670678 C>G,T), RS1003935422 (1:153669233 CA>C,CAA), RS1004051694 (1:153670927 C>A,G,T)

Disease associations

OMIM: gene MIM:603181 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295811 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.87	Kd	13.47	nM	CHEMBL5653589
7.87	ED50	13.47	nM	CHEMBL5653589
5.34	Kd	4537	nM	CHEMBL3752910
5.34	ED50	4537	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 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	2148582: Binding affinity to human ILF2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0135	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148582: Binding affinity to human ILF2 incubated for 45 mins by Kinobead based pull down assay	kd	4.5372	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	4
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance	3
cobaltous chloride	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
geraniol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
indirubin	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	decreases expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol AF	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Cannabidiol	affects cotreatment, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Cuprizone	decreases expression, affects cotreatment	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Furaldehyde	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118737	Binding	Binding affinity to ILF2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3E4	SEES3-1V human ILF2, clone1	Embryonic stem cell	Male
CVCL_A3E5	SEES3-1V human ILF2, clone2	Embryonic stem cell	Male
CVCL_A3E6	SEES3-1V human ILF2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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