ILF3

Summary

ILF3 (interleukin enhancer binding factor 3, HGNC:6038) is a protein-coding gene on chromosome 19p13.2, encoding Interleukin enhancer-binding factor 3 (Q12906). RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. It is a common-essential gene (DepMap: required in 97.4% of cancer cell lines).

This gene encodes a double-stranded RNA (dsRNA) binding protein that complexes with other proteins, dsRNAs, small noncoding RNAs, and mRNAs to regulate gene expression and stabilize mRNAs. This protein (NF90, ILF3) forms a heterodimer with a 45 kDa transcription factor (NF45, ILF2) required for T-cell expression of interleukin 2. This complex has been shown to affect the redistribution of nuclear mRNA to the cytoplasm. Knockdown of NF45 or NF90 protein retards cell growth, possibly by inhibition of mRNA stabilization. In contrast, an isoform (NF110) of this gene that is predominantly restricted to the nucleus has only minor effects on cell growth when its levels are reduced. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 3609 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 242 total — 2 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_017620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6038
Approved symbol	ILF3
Name	interleukin enhancer binding factor 3
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	NF90, MPHOSPH4, MPP4, NFAR-1, NFAR110, NFAR-2, TCP110, NF110, DRBP76, NFAR90, NF110b, NF90a, NF90c, NF90ctv, MPP4110
Ensembl gene	ENSG00000129351
Ensembl biotype	protein_coding
OMIM	603182
Entrez	3609

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 25 protein_coding, 6 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000250241, ENST00000407004, ENST00000585835, ENST00000586544, ENST00000587505, ENST00000587840, ENST00000587928, ENST00000587941, ENST00000588657, ENST00000589052, ENST00000589173, ENST00000589283, ENST00000589416, ENST00000589485, ENST00000589600, ENST00000589998, ENST00000590009, ENST00000590261, ENST00000590869, ENST00000591649, ENST00000592763, ENST00000593061, ENST00000593199, ENST00000899691, ENST00000899692, ENST00000899693, ENST00000938413, ENST00000938414, ENST00000938415, ENST00000938416, ENST00000938417, ENST00000938418, ENST00000938419, ENST00000938420, ENST00000970392

RefSeq mRNA: 24 — MANE Select: NM_017620 NM_001137673, NM_001394808, NM_001394809, NM_001394810, NM_001394811, NM_001394812, NM_001394813, NM_001394814, NM_001394815, NM_001394816, NM_001394817, NM_001394818, NM_001394819, NM_001394820, NM_001394821, NM_001394822, NM_001394823, NM_001394824, NM_001394826, NM_001394827, NM_004516, NM_012218, NM_017620, NM_153464

CCDS: CCDS12246, CCDS12247, CCDS45965, CCDS45966, CCDS45967

Canonical transcript exons

ENST00000588657 — 20 exons

Exon	Start	End
ENSE00000888280	10681993	10682192
ENSE00002746735	10689179	10692400
ENSE00002827736	10654346	10654487
ENSE00003535203	10683366	10683542
ENSE00003535375	10681219	10681329
ENSE00003550771	10679816	10679927
ENSE00003555276	10681019	10681130
ENSE00003559583	10683636	10683789
ENSE00003559974	10670516	10670608
ENSE00003564791	10682537	10682704
ENSE00003577532	10677163	10677310
ENSE00003581783	10679097	10679192
ENSE00003584923	10680346	10680443
ENSE00003604320	10683917	10683970
ENSE00003652852	10683125	10683262
ENSE00003677228	10671358	10671535
ENSE00003682615	10687346	10687708
ENSE00003687082	10688550	10688678
ENSE00003690921	10678613	10678704
ENSE00003787957	10670974	10671203

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 191.8387 / max 1731.8458, expressed in 1828 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173834	123.5889	1828
173833	63.8251	1822
173837	1.9545	318
173842	0.8074	510
173839	0.7361	441
173836	0.4440	188
173840	0.3396	146
173835	0.1430	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.23	gold quality
ventricular zone	UBERON:0003053	99.21	gold quality
cortical plate	UBERON:0005343	98.92	gold quality
embryo	UBERON:0000922	98.67	gold quality
sural nerve	UBERON:0015488	98.37	gold quality
left ovary	UBERON:0002119	98.24	gold quality
right ovary	UBERON:0002118	98.22	gold quality
right uterine tube	UBERON:0001302	98.19	gold quality
left lobe of thyroid gland	UBERON:0001120	98.03	gold quality
adenohypophysis	UBERON:0002196	98.01	gold quality
right lobe of thyroid gland	UBERON:0001119	97.97	gold quality
pituitary gland	UBERON:0000007	97.90	gold quality
left uterine tube	UBERON:0001303	97.89	gold quality
endocervix	UBERON:0000458	97.81	gold quality
body of uterus	UBERON:0009853	97.78	gold quality
cerebellar hemisphere	UBERON:0002245	97.70	gold quality
ectocervix	UBERON:0012249	97.68	gold quality
thyroid gland	UBERON:0002046	97.67	gold quality
cerebellar cortex	UBERON:0002129	97.67	gold quality
skin of abdomen	UBERON:0001416	97.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.62	gold quality
right testis	UBERON:0004534	97.59	gold quality
lymph node	UBERON:0000029	97.58	gold quality
left testis	UBERON:0004533	97.55	gold quality
granulocyte	CL:0000094	97.51	gold quality
metanephros cortex	UBERON:0010533	97.47	gold quality
skin of leg	UBERON:0001511	97.46	gold quality
spleen	UBERON:0002106	97.36	gold quality
secondary oocyte	CL:0000655	97.30	gold quality
paraflocculus	UBERON:0005351	97.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.28
E-GEOD-125970	no	3.48
E-HCAD-31	no	2.59

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
ACRV1	Activation
BIRC5	Activation
HLA-DQA1	Unknown
HLA-DRA	Repression
HLA-DRB1	Unknown
IL2	Activation
PLAU	Activation

Upstream regulators (CollecTRI, top): GLI2, ILF2, NR5A2, THRA

miRNA regulators (miRDB)

43 targeting ILF3, 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-1184	99.99	68.19	1458
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-10526-3P	97.86	64.97	1342

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• plays important role in protein priming of HBV polymerase (PMID:11958450)
• Nuclear export of this protein is required for interleukin-2 mRNA stabilization. (PMID:12504009)
• Results describe the expression of four isoforms of nuclear factor 90, including NF110, by cDNA cloning and mass spectrometric analysis of proteins isolated from human cells (PMID:12946349)
• nuclear export of ILF3 is mediated by exportin-5 and minihelix-containing RNA (PMID:14570900)
• the multiple cellular functions, i.e., translation control, interleukin-2 enhancer binding, or cell division, of ILF3 are fulfilled by alternatively spliced isoforms. (PMID:14654356)
• NF90 and NF110 engage RNA differentially and translocate from the nucleus to the cytoplasm in mitosis (PMID:15811368)
• ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with NF90 (PMID:16055709)
• The human Nuclear Factor 90 c-terminal variant protein encoded by ILF3 interacts with Rev to inhibit Rev-mediated RNA transport. (PMID:17125513)
• Our results show that perturbation Tat/TAR RNA interaction by the dsRNA binding nuclear factor 90 protein is sufficient to inhibit transcriptional activation of HIV-1. (PMID:17565699)
• DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes (PMID:18039850)
• CD28 costimulation activates AKT to phosphorylate NF90 at Ser647 and phosphorylation triggers NF90 to relocate to the cytoplasm and stabilize IL-2 mRNA. (PMID:18097023)
• NFARs exert influence on mRNA trafficking and the modulation of translation rates and may constitute an innate immune translational surveillance mechanism important in host defense countermeasures against virus infection (PMID:18337511)
• 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)
• MKP-1 upregulation by oxidative stress is potently influenced by increased mRNA stability and translation, mediated at least in part by the RNA-binding proteins HuR and NF90. (PMID:18490444)
• ILF-3, which has been known to regulate IL-2 expression in T cells, up-regulates synoviolin expression with GABPalpha in rheumatoid synovial cells (PMID:19116932)
• 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)
• NF90 inhibits influenza virus replication during the early phase of infection through direct interaction with viral NP. (PMID:19494010)
• our results identify NF45 and NF90 as novel regulators of HS4-dependent human IL13 transcription in response to T cell activation (PMID:20051514)
• Data suggest that physiologic DRBP76 expression, isoform distribution and subcellular localization are profoundly altered upon malignant transformation. (PMID:20668518)
• associations of rs2569512 of ILF3 to myocardial infarction among individuals stratified by the absence or presence of hypertension, diabetes mellitus and chronic kidney disease (PMID:21347509)
• Production of HIV particles is regulated by altering sub-cellular localization and dynamics of Rev induced by double-strand RNA binding protein. (PMID:21364984)
• NF90 binds the dengue virus RNA 3’ terminus and is a positive regulator of dengue virus. (PMID:21386893)
• The relationship between rs6929846 of BTN2A1 or rs2569512 of ILF3 and myocardial infarction is influenced by the serum concentrations of high density lipoprotein cholesterol and low density lipoprotein cholesterol, respectively. (PMID:21468600)
• The protein polymorphism of Ilf3/NF90 and the various subcellular localizations of their isoforms may partially explain the various functions previously reported for these proteins. (PMID:21811582)
• The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining (PMID:21969602)
• high expression of ERCC1, XPB and ILF3 was observed in human epithelial ovarian cancer (PMID:21971700)
• These data suggest that DRBP76, via its association with VP35, exerts an anti-Ebola virus function. (PMID:21987769)
• The unique C-terminal region of ILF3/NF110 is important for promoting survivin expression and for high affinity binding to YM155. (PMID:22442257)
• Data indicate that knockdown of interleukin enhancer-binding factor 3 (ILF3) leads to the increased levels of mature urokinase-type plasminogen activator (uPA) mRNA-targeting miRNAs miR-193a, miR-193b and miR-181a. (PMID:22986534)
• contributes to maintaining low levels of senescence-associated secretory phenotype factors in non-senescent cells (PMID:23117626)
• The function of NF90 in posttranscriptional gene regulation and microRNA biogenesis. [Review] (PMID:23965975)
• NF90 exerts antiviral activity through regulation of PKR phosphorylation and stress granules in infected cells. (PMID:24623135)
• 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)
• Suppression of NF90 caused a decrease in the half-life of cyclin E1 mRNA (PMID:25399696)
• the role of the human NF90 protein isoforms in DNA and RNA virus replication (PMID:25447144)
• Data indicate the role of cyclin-dependent kinase inhibitor 1A (p21) and interleukin enhancer binding factor 3 (ILF3) pathway in mediating the anti-leukemic activity of sodium dichloroacetate (DCA) in oncoprotein p53null leukemic cells. (PMID:25544776)
• NF45 and NF90 are novel higher-eukaryote-specific factors required for the maturation of 60S ribosomal subunits. (PMID:26240280)
• Taken together, our discovery of the function of TCP80 and RHA in regulating p53 IRES and p53 induction following DNA damage provides a better understanding of the mechanisms that regulate IRES-mediated p53 translation in response to genotoxic stress. (PMID:26273641)
• The RNA binding complexes NF45-NF90 and NF45-NF110 associate dynamically with the c-fos gene and function as transcriptional coactivators. (PMID:26381409)
• data suggest that lncRNA SALNR modulates cellular senescence at least partly through changing NF90 activity (PMID:26491010)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ilf3b	ENSDARG00000105177
mus_musculus	Ilf3	ENSMUSG00000032178
rattus_norvegicus	Ilf3	ENSRNOG00000022741
drosophila_melanogaster	loqs	FBGN0032515
drosophila_melanogaster	CG12493	FBGN0035571
drosophila_melanogaster	blanks	FBGN0035608
drosophila_melanogaster	Zn72D	FBGN0263603
caenorhabditis_elegans	zfr-1	WBGENE00022388

Paralogs (14): STAU2 (ENSG00000040341), ZFR (ENSG00000056097), ADAT1 (ENSG00000065457), ZFR2 (ENSG00000105278), STAU1 (ENSG00000124214), TARBP2 (ENSG00000139546), ADAD2 (ENSG00000140955), ILF2 (ENSG00000143621), ADAR (ENSG00000160710), ADAD1 (ENSG00000164113), STRBP (ENSG00000165209), PRKRA (ENSG00000180228), ADARB2 (ENSG00000185736), ADARB1 (ENSG00000197381)

Protein

Protein identifiers

Interleukin enhancer-binding factor 3 — Q12906 (reviewed: Q12906)

Alternative names: Double-stranded RNA-binding protein 76, M-phase phosphoprotein 4, Nuclear factor associated with dsRNA, Nuclear factor of activated T-cells 90 kDa, Translational control protein 80

All UniProt accessions (13): Q12906, K7EJ09, K7EKJ9, K7EKY0, K7ELV3, K7EM82, K7EMZ8, K7ENK6, K7EPG3, K7EQ75, K7EQR9, K7ER69, K7ERM6

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs. As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3’-UTR of target mRNAs. Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response. Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs. (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. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with FUS and SMN. Interacts (via C-terminus) with PRMT1. Forms a complex with ILF2. Can also bind to PRKDC/XRCC7: this may stabilize the interaction of PRKDC/XRCC7 and the heterodimeric complex of XRCC6/KU70 and XRCC5/KU80. Forms a heteromeric complex with ZNF346 and ILF3. Found in a nuclear export complex with XPO5, ILF3, Ran and double-stranded RNA or double-stranded minihelix VA1 RNA. Found in a nuclear export complex with XPO5, RAN, ILF3, ZNF346 and double-stranded RNA. Interacts with XPO5 and ZNF346. Forms a complex with ILF2, YLPM1, KHDRBS1, RBMX, NCOA5 and PPP1CA. Interacts with AGO1 and AGO2. Interacts with DHX36; this interaction occurs in a RNA-dependent manner. Interacts with ELAVL1; this interaction occurs in a RNA-dependent manner. Interacts with HAVCR2; this interaction promotes ILF3 ubiquitination and subsequent degradation.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated at Thr-188 and Thr-315 by PKR in response to certain RNA viruses. This phosphorylation results in the dissociation of ILF2 from the ILF2-ILF3 complex resulting in a cytoplasmic sequestration of ILF3 where it can bind to viral RNAs and impede viral replication. Methylated by protein arginine N-methyltransferase 1. Ubiquitinated at Lys-297 in a TRIM47-dependent manner; this ‘Lys-48’-linked ubiquitination promotes ILF3 degradation.

Miscellaneous. Dubious isoform produced through aberrant splice sites.

Isoforms (7)

UniProt ID	Names	Canonical?
Q12906-1	1, NFAR-2, ILF3-E	yes
Q12906-2	2, NFAR-1, DRBP76
Q12906-3	3
Q12906-4	4, DRBP76 Alpha, ILF3-A
Q12906-5	5, DRBP76 Delta, Gamma, ILF3-C
Q12906-6	6
Q12906-7	7

RefSeq proteins (24): NP_001131145, NP_001381737, NP_001381738, NP_001381739, NP_001381740, NP_001381741, NP_001381742, NP_001381743, NP_001381744, NP_001381745, NP_001381746, NP_001381747, NP_001381748, NP_001381749, NP_001381750, NP_001381751, NP_001381752, NP_001381753, NP_001381755, NP_001381756, NP_004507, NP_036350, NP_060090, NP_703194 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006561	DZF_dom	Domain
IPR014720	dsRBD_dom	Domain
IPR033099	DSRM1_ILF3	Domain
IPR043519	NT_sf	Homologous_superfamily
IPR049401	DZF_dom_N	Domain
IPR049402	DZF_dom_C	Domain

Pfam: PF00035, PF07528, PF20965

UniProt features (71 total): modified residue 19, compositionally biased region 12, splice variant 9, sequence conflict 8, region of interest 6, cross-link 4, domain 3, helix 3, strand 3, sequence variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7RJQ	X-RAY DIFFRACTION	1.72
3P1X	X-RAY DIFFRACTION	1.9
7RJM	X-RAY DIFFRACTION	2.1
2L33	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12906-F1	67.74	0.43

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 (23): 62, 100, 188, 190, 315, 382, 384, 460, 476, 477, 482, 592, 792, 810, 812, 816, 297, 348, 396, 489 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9762293	Regulation of CDH11 gene transcription
R-HSA-9833482	PKR-mediated signaling

MSigDB gene sets: 409 (showing top): E2F_Q4, MODULE_52, HORIUCHI_WTAP_TARGETS_DN, E2F4DP1_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, PAL_PRMT5_TARGETS_UP, HOFMANN_CELL_LYMPHOMA_UP, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_HDAC1, MORF_UBE2N

GO Biological Process (8): protein phosphorylation (GO:0006468), negative regulation of translation (GO:0017148), negative regulation of viral genome replication (GO:0045071), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), defense response to virus (GO:0051607), spliceosome-depend formation of circular RNA (GO:0160091), symbiont entry into host cell (GO:0046718)

GO Molecular Function (7): virus receptor activity (GO:0001618), DNA binding (GO:0003677), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), mRNA 3’-UTR AU-rich region binding (GO:0035925), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), membrane (GO:0016020), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of CDH11 Expression and Function	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
DNA-templated transcription	2
regulation of DNA-templated transcription	2
nucleic acid binding	2
RNA binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
phosphorylation	1
protein modification process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
defense response	1
response to virus	1
mRNA splicing, via spliceosome	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
mRNA 3’-UTR binding	1
binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

3148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ILF3	ILF2	Q12905	988
ILF3	HNRNPL	P14866	972
ILF3	HNRNPA2B1	P22626	940
ILF3	FUS	P35637	927
ILF3	HNRNPH1	P31943	906
ILF3	XPO5	Q9HAV4	869
ILF3	HNRNPM	P52272	869
ILF3	EIF2AK2	P19525	865
ILF3	HNRNPC	P07910	854
ILF3	HNRNPH2	P55795	832
ILF3	NONO	P30807	765
ILF3	MATR3	P43243	765
ILF3	DHX9	Q08211	754
ILF3	DICER1	Q9UPY3	709
ILF3	HNRNPD	P07029	697

IntAct

325 interactions, top by confidence:

A	B	Type	Score
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
HNRNPL	HNRNPA2B1	psi-mi:“MI:0914”(association)	0.630
HNRNPL	HNRNPA2B1	psi-mi:“MI:0914”(association)	0.620
ILF3	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.560
ILF3	NS	psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
M	ILF3	psi-mi:“MI:0915”(physical association)	0.500
ILF3	M	psi-mi:“MI:0914”(association)	0.500
HNRNPL	ILF3	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
CUEDC1	ILF3	psi-mi:“MI:0915”(physical association)	0.400
ILF3	SPARC	psi-mi:“MI:0915”(physical association)	0.400
USP12	ILF3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1314): ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), PLSCR1 (Two-hybrid), RBPMS (Two-hybrid), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), ILF3 (Affinity Capture-MS)

ESM2 similar proteins: A5D7P8, A6QLK2, F1LQ48, O55047, O95628, P25916, P35226, P59326, P97855, Q08CW1, Q0VCY1, Q0VCZ3, Q12906, Q13148, Q13283, Q1ECX4, Q32KX7, Q32LC7, Q3SWT1, Q3ZBD9, Q4R5D9, Q5FVP2, Q5PRC7, Q5R601, Q5R8L2, Q5RB87, Q5SDR3, Q5U2U0, Q5ZLN5, Q64213, Q66K94, Q6DE02, Q6NRF9, Q86UE8, Q8BGW5, Q8BT14, Q8C0V0, Q8R2Y9, Q90ZY6, Q91YT7

Diamond homologs: O88532, Q08E27, Q0VD35, Q12906, Q562A2, Q5R6Y5, Q5REX3, Q5U231, Q5ZIL4, Q6DCD0, Q6DD04, Q6GL57, Q6GPM1, Q6NXA4, Q6PCR6, Q7TP98, Q91550, Q91WM1, Q96KR1, Q96SI9, Q9H898, Q9JIL3, Q9JKU6, Q9UPR6, Q9Z1X4, A2RFW8, A8AWC2, B5XKB7, B8GAM6, C0MCR4, P0DF14, P0DF15, P51400, P55265, P55266, P66670, P66672, P78563, P97473, P97616

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AKT	“up-regulates activity”	ILF3	phosphorylation
PRKCB	“up-regulates activity”	ILF3	phosphorylation
AKT1	“up-regulates activity”	ILF3	phosphorylation
ILF3	“form complex”	NF90-NF45	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 226 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
SARS-CoV-1 modulates host translation machinery	6	11.8×	2e-04
Nonsense-Mediated Decay (NMD)	7	10.4×	1e-04
mRNA Polyadenylation	18	10.1×	6e-11
SARS-CoV-1-host interactions	9	10.1×	2e-05
SARS-CoV-2 modulates host translation machinery	7	10.0×	2e-04
Eukaryotic Translation Initiation	5	9.8×	3e-03
Cap-dependent Translation Initiation	5	9.8×	3e-03
Formation of the ternary complex, and subsequently, the 43S complex	7	9.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	6	30.2×	9e-06
alternative mRNA splicing, via spliceosome	6	20.5×	5e-05
negative regulation of mRNA splicing, via spliceosome	5	19.4×	4e-04
stress granule assembly	6	18.3×	8e-05
regulation of alternative mRNA splicing, via spliceosome	10	12.4×	3e-06
mRNA export from nucleus	8	12.0×	4e-05
regulation of translational initiation	5	11.9×	3e-03
mitophagy	7	11.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	184
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2423585	NC_000002.11:g.(?202501451)(202633608_?)del	Pathogenic
375383	NM_033066.3(MPP4):c.946T>C (p.Trp316Arg)	Pathogenic

SpliceAI

2701 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10654484:CAAGG:C	donor_loss	1.0000
19:10654485:AAGGT:A	donor_loss	1.0000
19:10654486:AGG:A	donor_loss	1.0000
19:10654487:GGT:G	donor_loss	1.0000
19:10654488:G:GG	donor_gain	1.0000
19:10654488:GT:G	donor_loss	1.0000
19:10654489:T:A	donor_loss	1.0000
19:10670515:GA:G	acceptor_gain	1.0000
19:10670968:CCCTA:C	acceptor_loss	1.0000
19:10670969:CCTA:C	acceptor_loss	1.0000
19:10670970:CTAG:C	acceptor_loss	1.0000
19:10670971:TAGC:T	acceptor_loss	1.0000
19:10670972:A:AG	acceptor_gain	1.0000
19:10670972:A:AT	acceptor_loss	1.0000
19:10670973:G:GG	acceptor_gain	1.0000
19:10670973:GC:G	acceptor_gain	1.0000
19:10670973:GCGTC:G	acceptor_gain	1.0000
19:10671199:GCTGG:G	donor_gain	1.0000
19:10671201:TGGG:T	donor_loss	1.0000
19:10671202:GG:G	donor_gain	1.0000
19:10671203:GG:G	donor_gain	1.0000
19:10671203:GGTA:G	donor_loss	1.0000
19:10671204:G:GA	donor_loss	1.0000
19:10671204:G:GG	donor_gain	1.0000
19:10671205:T:A	donor_loss	1.0000
19:10671353:CTCA:C	acceptor_loss	1.0000
19:10671355:CA:C	acceptor_loss	1.0000
19:10671356:A:AG	acceptor_gain	1.0000
19:10671356:AG:A	acceptor_gain	1.0000
19:10671357:G:A	acceptor_gain	1.0000

AlphaMissense

5837 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10671001:G:C	D11H	1.000
19:10671002:A:C	D11A	1.000
19:10671002:A:T	D11V	1.000
19:10671034:T:C	Y22H	1.000
19:10671034:T:G	Y22D	1.000
19:10671037:C:T	P23S	1.000
19:10671038:C:A	P23Q	1.000
19:10671053:T:A	L28Q	1.000
19:10671053:T:C	L28P	1.000
19:10671062:T:A	V31D	1.000
19:10671065:A:C	Q32P	1.000
19:10671066:G:C	Q32H	1.000
19:10671066:G:T	Q32H	1.000
19:10671086:A:T	E39V	1.000
19:10671087:G:C	E39D	1.000
19:10671087:G:T	E39D	1.000
19:10671091:G:C	A41P	1.000
19:10671092:C:A	A41E	1.000
19:10671095:T:A	L42H	1.000
19:10671095:T:C	L42P	1.000
19:10671095:T:G	L42R	1.000
19:10671097:A:G	K43E	1.000
19:10671098:A:T	K43I	1.000
19:10671099:A:C	K43N	1.000
19:10671099:A:T	K43N	1.000
19:10671104:T:A	V45E	1.000
19:10671106:T:C	S46P	1.000
19:10671390:T:A	L89Q	1.000
19:10671390:T:C	L89P	1.000
19:10671395:G:A	G91R	1.000

dbSNP variants (sampled 300 via entrez): RS1000108372 (19:10652476 A>G), RS1000131095 (19:10666195 G>C), RS1000247357 (19:10688890 C>G,T), RS1000327142 (19:10661056 A>G), RS1000378202 (19:10660806 T>G), RS1000384819 (19:10675259 T>G), RS1000464346 (19:10665145 T>G), RS1000608634 (19:10655535 A>G,T), RS1000618445 (19:10669433 G>T), RS1000675365 (19:10656563 C>G), RS1000690525 (19:10692424 C>A,G,T), RS1000713933 (19:10659901 A>C,G), RS1000869936 (19:10664524 C>G), RS1000889708 (19:10679245 T>C), RS1000958155 (19:10655653 T>A)

Disease associations

OMIM: gene MIM:603182 | disease phenotypes: MIM:607225, MIM:614424

GenCC curated gene-disease

Mondo (4): infantile-onset ascending hereditary spastic paralysis (MONDO:0011797), Joubert syndrome 14 (MONDO:0013745), intellectual disability (MONDO:0001071), strabismus (MONDO:0003432)

Orphanet (2): Infantile-onset ascending hereditary spastic paralysis (Orphanet:293168), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001762_723	Obesity-related traits	7.000000e-06
GCST002647_162	Height	8.000000e-11
GCST002702_28	Height	2.000000e-16
GCST002738_5	Psoriasis	3.000000e-07
GCST002874_22	Psoriasis	2.000000e-06
GCST003268_37	Psoriasis vulgaris	8.000000e-07
GCST004991_1	White matter microstructure in first episode schizophrenia (left inferior parietal cortex)	9.000000e-08
GCST005527_36	Psoriasis	3.000000e-17
GCST006959_18	Rheumatoid arthritis	9.000000e-10
GCST007400_34	Systemic lupus erythematosus	7.000000e-06
GCST007576_284	Chronotype	1.000000e-12
GCST008103_119	Bipolar disorder	5.000000e-06
GCST010456_3	Anthracycline-induced cardiotoxicity in early breast cancer	5.000000e-06
GCST011624_3	Tau burden	6.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:1001494	psoriasis vulgaris
EFO:0005674	white matter microstructure measurement
EFO:0008328	chronotype measurement
EFO:0005257	response to anthracycline-based chemotherapy
EFO:1001482	cardiotoxicity
EFO:0004760	t-tau measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D013285	Strabismus	C10.292.562.887; C11.590.810
C537217	Hereditary spastic paralysis, infantile onset ascending (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465305 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 366 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2105734	SEPANTRONIUM BROMIDE	2	366

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs76966440	ILF3		0.00	0

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.76	Kd	17.44	nM	CHEMBL5653589
7.76	ED50	17.44	nM	CHEMBL5653589
6.79	Kd	163	nM	CHEMBL5411686
6.24	Kd	571	nM	SEPANTRONIUM BROMIDE
5.03	Kd	9386	nM	CHEMBL3752910
5.03	ED50	9386	nM	CHEMBL3752910

PubChem BioAssay actives

4 with measured affinity, of 10 total; 4 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	2148583: Binding affinity to human ILF3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0174	uM
1,3-dimethylnaphtho[2,3-f]benzimidazol-3-ium-4,11-dione iodide	2025132: Binding affinity to ILF3 (unknown origin) assessed as dissociation constant at upto 1 uM by SPR method	kd	0.1630	uM
1-(2-methoxyethyl)-2-methyl-3-(pyrazin-2-ylmethyl)benzo[f]benzimidazol-3-ium-4,9-dione bromide	2025132: Binding affinity to ILF3 (unknown origin) assessed as dissociation constant at upto 1 uM by SPR method	kd	0.5710	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148583: Binding affinity to human ILF3 incubated for 45 mins by Kinobead based pull down assay	kd	9.3857	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Tretinoin	decreases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	decreases expression	3
bisphenol F	affects cotreatment, decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Caffeine	decreases phosphorylation, increases expression	2
Ozone	increases oxidation, affects expression, increases abundance, affects cotreatment	2
Valproic Acid	affects expression, decreases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
trichostatin A	decreases expression, affects cotreatment	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
sulindac sulfide	decreases expression	1
coumarin	increases phosphorylation	1
cupric oxide	decreases phosphorylation	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
tamibarotene	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5379142	Binding	Binding affinity to ILF3 (unknown origin) assessed as dissociation constant at upto 1 uM by SPR method	Pioneering 4,11-Dioxo-4,11-dihydro-1H-anthra[2,3-d]imidazol-3-ium Compounds as Promising Survivin Inhibitors by Targeting ILF3/NF110 for Cancer Therapy. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00461656	PHASE4	COMPLETED	Povidone-iodine Antisepsis for Strabismus Surgery
NCT01901588	PHASE4	COMPLETED	Efficacy of Single-Shot Dexmedetomidine Versus Placebo in Preventing Pediatric Emergence Delirium in Strabismus Surgery
NCT02379546	PHASE4	COMPLETED	The Effect of Anaesthesia Depth on Oculo-cardiac Reflex
NCT03349515	PHASE4	COMPLETED	The Effect of Povidone-iodine Ophthalmic Surgical Prep Solution on Respiration in Children Undergoing Strabismus Surgery With General Anesthesia.
NCT04549844	PHASE4	UNKNOWN	Peribulbar Block for Prevention of Oculocardiac Reflex
NCT06035757	PHASE4	RECRUITING	The Occurrence of Emergence Agitation in Pediatric Strabismus Surgery
NCT06560268	PHASE4	NOT_YET_RECRUITING	Low Flow Anesthesia in Children Undergoing Strabismus Surgery
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00000128	PHASE3	UNKNOWN	A Trial of Bifocals in Myopic Children With Esophoria
NCT00001864	PHASE3	COMPLETED	Amblyopia (Lazy Eye) Treatment Study
NCT00038753	PHASE3	UNKNOWN	Vision In Preschoolers Study (VIP Study)
NCT01584843	PHASE3	COMPLETED	Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus
NCT04060771	PHASE3	UNKNOWN	Post-Operative Nausea and Vomiting in Children Submitted to Strabismus Surgery
NCT06863675	PHASE3	NOT_YET_RECRUITING	Highly Aspherical Lenslet (HAL) and Binocular Vision (BV) Disorders [HALT X(T) Study]
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00478907	PHASE2	COMPLETED	Prevention of Complications of Eye Surgery
NCT06689943	PHASE2	NOT_YET_RECRUITING	Pain After Strabismus Surgery
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00917982	PHASE1	UNKNOWN	The Effect of Vision Therapy/Orthoptic on Motor & Sensory Status of the 3 to 7 Years Old Strabismic Patients
NCT02246556	PHASE1	TERMINATED	Dichoptic Virtual Reality Therapy for Amblyopia in Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities