IL4I1

Summary

IL4I1 (interleukin 4 induced 1, HGNC:19094) is a protein-coding gene on chromosome 19q13.33, encoding L-amino-acid oxidase (Q96RQ9). Secreted L-amino-acid oxidase that acts as a key immunoregulator.

This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5’ UTR with the overlapping NUP62 gene.

Source: NCBI Gene 259307 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 307 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_152899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19094
Approved symbol	IL4I1
Name	interleukin 4 induced 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FIG1
Ensembl gene	ENSG00000104951
Ensembl biotype	protein_coding
OMIM	609742
Entrez	259307

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000341114, ENST00000391826, ENST00000593956, ENST00000595948, ENST00000596011, ENST00000596022, ENST00000597295, ENST00000601717, ENST00000892974, ENST00000892975

RefSeq mRNA: 5 — MANE Select: NM_152899 NM_001258017, NM_001258018, NM_001385639, NM_152899, NM_172374

CCDS: CCDS12786, CCDS12787

Canonical transcript exons

ENST00000391826 — 8 exons

Exon	Start	End
ENSE00003214936	49896835	49896887
ENSE00003527299	49891405	49891473
ENSE00003586904	49890971	49891107
ENSE00003609041	49889654	49890600
ENSE00003656722	49894268	49894469
ENSE00003657035	49896148	49896182
ENSE00003693930	49895068	49895180
ENSE00003790590	49895815	49896053

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 88.02.

FANTOM5 (CAGE): breadth broad, TPM avg 9.7818 / max 489.4238, expressed in 557 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182118	33.4684	1817
182117	10.2059	1529
182110	9.5293	532
182112	0.1269	51
182111	0.0845	47
182109	0.0411	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.02	gold quality
left testis	UBERON:0004533	86.55	gold quality
vermiform appendix	UBERON:0001154	85.73	gold quality
right testis	UBERON:0004534	84.81	gold quality
testis	UBERON:0000473	83.84	gold quality
caecum	UBERON:0001153	76.03	gold quality
amniotic fluid	UBERON:0000173	74.59	gold quality
lymph node	UBERON:0000029	74.19	gold quality
monocyte	CL:0000576	74.03	gold quality
cartilage tissue	UBERON:0002418	73.83	silver quality
leukocyte	CL:0000738	73.67	gold quality
granulocyte	CL:0000094	72.44	gold quality
decidua	UBERON:0002450	72.18	gold quality
stromal cell of endometrium	CL:0002255	72.01	gold quality
buccal mucosa cell	CL:0002336	71.50	gold quality
tendon of biceps brachii	UBERON:0008188	68.70	gold quality
pancreatic ductal cell	CL:0002079	67.79	silver quality
gall bladder	UBERON:0002110	66.74	gold quality
parotid gland	UBERON:0001831	66.50	gold quality
heart right ventricle	UBERON:0002080	64.80	gold quality
tonsil	UBERON:0002372	64.75	gold quality
mucosa of transverse colon	UBERON:0004991	64.20	gold quality
right uterine tube	UBERON:0001302	63.70	gold quality
right coronary artery	UBERON:0001625	63.66	gold quality
spleen	UBERON:0002106	63.37	gold quality
metanephros cortex	UBERON:0010533	63.15	gold quality
duodenum	UBERON:0002114	62.67	gold quality
fallopian tube	UBERON:0003889	62.57	gold quality
oviduct epithelium	UBERON:0004804	62.32	gold quality
islet of Langerhans	UBERON:0000006	62.02	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	1451.09
E-MTAB-10287	yes	594.10
E-MTAB-6505	yes	516.47
E-CURD-89	yes	490.60
E-MTAB-8142	yes	101.16
E-CURD-88	yes	20.38
E-CURD-46	yes	13.59
E-CURD-122	yes	12.75
E-MTAB-6701	yes	12.38
E-MTAB-8498	yes	11.15
E-ANND-3	yes	8.98
E-MTAB-6678	yes	7.05
E-CURD-112	no	3.27

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 25)

• genomic structure, cDNA sequence, chromosome location and RNA expression in immune tissues (PMID:12031486)
• is activated in primary mediastinal large B-cell lymphoma, which might be due to a constitutive activation of a cytokine signaling pathway (PMID:12446450)
• hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4(+) and CD8(+) T cells. In contrast, memory T cells were more strongly affected by hIL4I1 and its catabolite H(2)O(2) than naive T cells (PMID:17356132)
• strong IL4I1 expression is associated with B-cell lymphomas. (PMID:19436310)
• participates in the downregulation of Th1 inflammation (PMID:20683900)
• IL4I1 plays a distinct role compared to other antibacterial enzymes produced by mononuclear phagocytes. (PMID:23355881)
• IL4I1 upregulation in human Th17 cells limits their TCR-mediated expansion not only by blocking the molecular pathway involved in the activation of the IL-2 promoter, but also by maintaining high levels of Tob1, which impairs entry into the cell cycle. (PMID:24307243)
• The immunosuppressive enzyme IL4I1 expressed differentially in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells. (PMID:25446972)
• reviewed SNPs of the IL4I1 isoform 1, which is expressed in lymphoid tissue; the N92D SNP leads to a hyperactive enzyme, while the R102G mutation is hypomorphic; show that IL4I1 activity is not only directed against phenylalanine, as initially described, but also at a lower level against arginine (PMID:26673964)
• the presence of IL4I1 during T-cell activation decreases early signaling events downstream of t-cell receptor stimulation, resulting in global T-cell inhibition which is more pronounced when there is CD28 costimulation. (PMID:28891065)
• Data showed proteome changes in alveolar epithelial cells type II exposed to an infection with A. fumigatus with IL4I1 showing the most prominent increase in abundance both, in terms of relative abundance as well as activity. Also, in the infected lungs, there was levels of IL4I1 metabolic products. (PMID:28951444)
• these data show that IL4I1+ cells shape the T-cell compartment and are associated with a higher risk of poor outcome in melanoma, supporting a key role for IL4I1 in immune evasion. (PMID:30048651)
• Lnc-C/EBPbeta Modulates Differentiation of MDSCs Through Downregulating IL4i1 With C/EBPbeta LIP and WDR5. (PMID:31379854)
• IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. (PMID:32818467)
• IL4I1-driven AHR signature: a new avenue for cancer therapy. (PMID:33692337)
• What role for AHR activation in IL4I1-mediated immunosuppression ? (PMID:34026337)
• Integrated analysis reveals the participation of IL4I1, ITGB7, and FUT7 in reshaping the TNBC immune microenvironment by targeting glycolysis. (PMID:34134578)
• Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression. (PMID:34717685)
• Pan-cancer analysis combined with experimental validation revealed IL4I1 as an immunological and prognostic biomarker. (PMID:35952516)
• IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma. (PMID:36056935)
• IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike. (PMID:36131918)
• Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor. (PMID:36834576)
• Knockdown of IL4I1 Improved High Glucose-evoked Insulin Resistance in HepG2 Cells by Alleviating Inflammation and Lipotoxicity Through AHR Activation. (PMID:36913096)
• IL4i1 and IDO1: Oxidases that control a tryptophan metabolic nexus in cancer. (PMID:37196768)
• IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy. (PMID:38250074)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	mao	ENSDARG00000023712
danio_rerio	zgc:66484	ENSDARG00000030478
danio_rerio	si:ch211-127i16.2	ENSDARG00000092976
mus_musculus	Il4i1	ENSMUSG00000074141
rattus_norvegicus	Il4i1	ENSRNOG00000020148
drosophila_melanogaster	CG10561	FBGN0002036
drosophila_melanogaster	CG7737	FBGN0033584
drosophila_melanogaster	CG5653	FBGN0035943
drosophila_melanogaster	CG7460	FBGN0036749
drosophila_melanogaster	CG6034	FBGN0036750
drosophila_melanogaster	CG8032	FBGN0037606
drosophila_melanogaster	shps	FBGN0286199
caenorhabditis_elegans		WBGENE00000137
caenorhabditis_elegans	spr-5	WBGENE00005010
caenorhabditis_elegans		WBGENE00011615

Paralogs (7): KDM1A (ENSG00000004487), MAOB (ENSG00000069535), SMOX (ENSG00000088826), PPOX (ENSG00000143224), PAOX (ENSG00000148832), KDM1B (ENSG00000165097), MAOA (ENSG00000189221)

Protein

Protein identifiers

L-amino-acid oxidase — Q96RQ9 (reviewed: Q96RQ9)

Alternative names: Interleukin-4-induced protein 1, Protein Fig-1

All UniProt accessions (6): Q96RQ9, M0QXY7, M0QYH9, M0QYW8, M0R1L1, M0R2S9

UniProt curated annotations — full annotation on UniProt →

Function. Secreted L-amino-acid oxidase that acts as a key immunoregulator. Has preference for L-aromatic amino acids: converts phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) to phenylpyruvic acid (PP), hydroxyphenylpyruvic acid (HPP), and indole-3-pyruvic acid (I3P), respectively. Also has weak L-arginine oxidase activity. Acts as a negative regulator of anti-tumor immunity by mediating Trp degradation via an indole pyruvate pathway that activates the transcription factor AHR. IL4I1-mediated Trp catabolism generates I3P, giving rise to indole metabolites (indole-3-acetic acid (IAA) and indole-3-aldehyde (I3A)) and kynurenic acid, which act as ligands for AHR, a ligand-activated transcription factor that plays important roles in immunity and cancer. AHR activation by indoles following IL4I1-mediated Trp degradation enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity. Also has an immunoregulatory function in some immune cells, probably by mediating Trp degradation and promoting downstream AHR activation: inhibits T-cell activation and proliferation, promotes the differentiation of naive CD4(+) T-cells into FOXP3(+) regulatory T-cells (Treg) and regulates the development and function of B-cells. Also regulates M2 macrophage polarization by inhibiting T-cell activation. Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2.

Subcellular location. Secreted. Lysosome. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Primarily found in immune tissues, with the highest expression in lymph nodes and spleen. Present in germinal center macrophages and inflammatory myeloid cells and antigen-presenting cells (at protein level). Also present in spermatozoa (at protein level). Highly expressed in primary mediastinal large B-cell lymphoma, a specific subtype of diffuse large B-cell lymphoma. Expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages.

Post-translational modifications. N-glycosylated.

Activity regulation. L-amino-acid oxidase activity toward phenylalanine (Phe) is specfically inhibited by a number of Phe derivatives, such as Cp3 (ethyl 3-(2,6-dichlorophenyl)-2-(piperidin-1-yl)propanoate) or Cp2-SO4. Cp3 is a very potent inhibitor for activity toward phenylalanine but is toxic. In contrast, Cp2-SO4 is less efficient but not toxic and is able to reverse immunosuppressive action of IL4I1 in vitro.

Induction. By IL4/interleukin-4. Expression is up-regulated in numerous cancer and metastasis: expression is induced by immune checkpoint blockade.

Pathway. Amino-acid degradation; L-tryptophan degradation via pyruvate pathway.

Miscellaneous. Uses the promoter of the upstream NUP62 gene and shares the first 2 non-coding exons with NUP62.

Similarity. Belongs to the flavin monoamine oxidase family. FIG1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96RQ9-1	1	yes
Q96RQ9-2	2, IL4I1_2

RefSeq proteins (5): NP_001244946, NP_001244947, NP_001372568, NP_690863, NP_758962 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001613	Flavin_amine_oxidase	Family
IPR002937	Amino_oxidase	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR050281	Flavin_monoamine_oxidase	Family

Pfam: PF01593

Catalyzed reactions (Rhea), 5 shown:

• an L-alpha-amino acid + O2 + H2O = a 2-oxocarboxylate + H2O2 + NH4(+) (RHEA:13781)
• L-arginine + O2 + H2O = 5-guanidino-2-oxopentanoate + H2O2 + NH4(+) (RHEA:51404)
• L-phenylalanine + O2 + H2O = 3-phenylpyruvate + H2O2 + NH4(+) (RHEA:61240)
• L-tryptophan + O2 + H2O = indole-3-pyruvate + H2O2 + NH4(+) (RHEA:61244)
• L-tyrosine + O2 + H2O = 3-(4-hydroxyphenyl)pyruvate + H2O2 + NH4(+) (RHEA:61248)

UniProt features (26 total): binding site 10, glycosylation site 4, sequence variant 3, sequence conflict 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, region of interest 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RQ9-F1	86.80	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (10): 398; 481; 488–493; 488–489; 69–70; 89–90; 97; 113–116; 116; 287

Disulfide bonds (1): 36–199

Glycosylation sites (4): 54, 134, 220, 559

Mutagenesis-validated functional residues (1):

Position	Phenotype
481	abolished l-amino-acid oxidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8964208	Phenylalanine metabolism

MSigDB gene sets: 314 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, E2F_Q4, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, E2F4DP1_01, GOBP_B_CELL_ACTIVATION, GOCC_SECRETORY_GRANULE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, CMYB_01, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION

GO Biological Process (15): adaptive immune response (GO:0002250), regulation of adaptive immune response (GO:0002819), negative regulation of T cell mediated immune response to tumor cell (GO:0002841), L-phenylalanine catabolic process (GO:0006559), L-tryptophan catabolic process (GO:0006569), L-tyrosine catabolic process (GO:0006572), amino acid catabolic process (GO:0009063), obsolete L-tryptophan catabolic process to indole-3-acetate (GO:0019440), negative regulation of T cell proliferation (GO:0042130), regulation of B cell differentiation (GO:0045577), positive regulation of regulatory T cell differentiation (GO:0045591), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of T cell activation (GO:0050868), immune system process (GO:0002376), aromatic amino acid metabolic process (GO:0009072)

GO Molecular Function (4): L-amino-acid oxidase activity (GO:0001716), L-phenylalaine oxidase activity (GO:0106329), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (7): acrosomal vesicle (GO:0001669), immunological synapse (GO:0001772), extracellular region (GO:0005576), lysosome (GO:0005764), sperm midpiece (GO:0097225), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phenylalanine and tyrosine metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
aromatic amino acid catabolic process	3
L-amino acid catabolic process	3
proteinogenic amino acid catabolic process	3
amino acid metabolic process	2
immune response	1
adaptive immune response	1
regulation of immune response	1
T cell mediated immune response to tumor cell	1
negative regulation of T cell mediated immunity	1
negative regulation of immune response to tumor cell	1
regulation of T cell mediated immune response to tumor cell	1
indole-containing compound catabolic process	1
catabolic process	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
B cell differentiation	1
regulation of lymphocyte differentiation	1
regulation of B cell activation	1
regulatory T cell differentiation	1
positive regulation of T cell differentiation	1
regulation of regulatory T cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
biological_process	1
carboxylic acid metabolic process	1
primary methylamine oxidase activity	1
L-amino-acid oxidase activity	1
binding	1
catalytic activity	1
secretory granule	1
plasma membrane	1
lytic vacuole	1

Protein interactions and networks

STRING

1400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL4I1	NUP62	P37198	863
IL4I1	FUT1	P19526	761
IL4I1	CRISP1	P54107	677
IL4I1	PLB1	Q6P1J6	662
IL4I1	CRISP2	P16562	653
IL4I1	CRISP3	P54108	621
IL4I1	LTA4H	P09960	601
IL4I1	KLK1	P06870	590
IL4I1	IL4	P05112	556
IL4I1	CD247	P20963	528
IL4I1	SH2D3A	Q9BRG2	517
IL4I1	MAOA	P21397	488
IL4I1	PXDN	Q92626	479
IL4I1	PXDNL	A1KZ92	478
IL4I1	DAO	P14920	476

IntAct

10 interactions, top by confidence:

A	B	Type	Score
IL4I1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
IL4I1	OPTN	psi-mi:“MI:0915”(physical association)	0.560
IL4I1	PHB1	psi-mi:“MI:0915”(physical association)	0.400
ATG16L1		psi-mi:“MI:0914”(association)	0.350
TRIM54	IL4I1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): IL4I1 (Proximity Label-MS), IL4I1 (Two-hybrid), IL4I1 (Affinity Capture-RNA), IL4I1 (Affinity Capture-RNA), TMPRSS13 (Co-localization), TMPRSS13 (Affinity Capture-Western), IL4I1 (Affinity Capture-Western), GLG1 (Affinity Capture-MS), IL4I1 (Affinity Capture-MS), ITGB7 (Affinity Capture-MS), P4HB (Affinity Capture-MS), SLC25A3 (Affinity Capture-MS), SLC25A5 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMPRSS13 (Affinity Capture-MS)

ESM2 similar proteins: A0A3G9HHK2, A2Y6Z7, B3MJ16, B3N6Y7, B3NN96, B4GGF2, B4GHE3, B4HT15, B4I7X1, B4JVW6, B4NWI1, B4P8E0, B4QGM0, B4QHB1, O09046, O59759, P16393, P20933, P23225, P30919, P48441, Q0C8L9, Q0VCR7, Q21697, Q28XQ5, Q28Y14, Q43155, Q4R6C4, Q53WK1, Q567W6, Q5R889, Q5REF9, Q64191, Q67WN8, Q84WB7, Q8BJM7, Q8MR45, Q96HN2, Q96RQ9, Q9LY71

Diamond homologs: A0A024BTN9, A0A2U8QPE6, A2XDA1, A6MFL0, A8QL51, A8QL52, A8QL58, B0VXW0, B3EWI9, B5AR80, B5U6Y8, C0HJE7, F8S0Z5, G8XQX1, J7H670, K9N7B7, O08615, O09046, O24164, O34363, O60341, O93364, P0C2D1, P0C2D2, P0C2D3, P0C2D4, P0C2D5, P0C2D6, P0C2D7, P0CC17, P0CJ40, P0DI84, P0DI87, P0DI88, P0DI89, P0DI91, P0DPS2, P0DQH9, P0DV78, P28553

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	218
Likely benign	64
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4752	NM_016553.5(NUP62):c.1172A>C (p.Gln391Pro)	Pathogenic

SpliceAI

2147 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49890608:C:CT	acceptor_gain	1.0000
19:49890969:A:AC	donor_gain	1.0000
19:49890970:C:CA	donor_gain	1.0000
19:49890970:CTGG:C	donor_gain	1.0000
19:49890970:CTGGA:C	donor_gain	1.0000
19:49891103:TATTC:T	acceptor_gain	1.0000
19:49891104:ATTC:A	acceptor_gain	1.0000
19:49891105:TTC:T	acceptor_gain	1.0000
19:49891108:C:CA	acceptor_loss	1.0000
19:49891108:C:CC	acceptor_gain	1.0000
19:49891400:CTTA:C	donor_loss	1.0000
19:49891401:TTAC:T	donor_loss	1.0000
19:49891402:TA:T	donor_loss	1.0000
19:49891403:A:AC	donor_gain	1.0000
19:49891404:C:CC	donor_gain	1.0000
19:49891474:C:CC	acceptor_gain	1.0000
19:49891474:CTGTT:C	acceptor_loss	1.0000
19:49891477:T:TC	acceptor_gain	1.0000
19:49891479:G:C	acceptor_gain	1.0000
19:49894264:CCAC:C	donor_loss	1.0000
19:49894264:CCACC:C	donor_gain	1.0000
19:49894266:A:AC	donor_gain	1.0000
19:49894266:AC:A	donor_gain	1.0000
19:49894267:C:CC	donor_gain	1.0000
19:49894267:CC:C	donor_gain	1.0000
19:49894267:CCT:C	donor_gain	1.0000
19:49894267:CCTGG:C	donor_gain	1.0000
19:49894468:TC:T	acceptor_gain	1.0000
19:49894469:CC:C	acceptor_gain	1.0000
19:49894470:C:CC	acceptor_gain	1.0000

AlphaMissense

3689 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49890044:A:G	W444R	0.988
19:49890044:A:T	W444R	0.988
19:49890042:C:A	W444C	0.986
19:49890042:C:G	W444C	0.986
19:49890254:A:G	S374P	0.985
19:49890012:A:C	F454L	0.983
19:49890012:A:T	F454L	0.983
19:49890014:A:G	F454L	0.983
19:49894421:G:C	F138L	0.983
19:49894421:G:T	F138L	0.983
19:49894423:A:G	F138L	0.983
19:49889909:A:G	W489R	0.982
19:49889909:A:T	W489R	0.982
19:49895856:C:A	G71W	0.980
19:49890284:A:G	W364R	0.979
19:49890284:A:T	W364R	0.979
19:49890297:G:C	F359L	0.979
19:49890297:G:T	F359L	0.979
19:49890299:A:G	F359L	0.979
19:49889902:T:A	E491V	0.978
19:49890282:C:A	W364C	0.978
19:49890282:C:G	W364C	0.978
19:49890405:G:C	S323R	0.978
19:49890405:G:T	S323R	0.978
19:49890407:T:G	S323R	0.978
19:49889938:G:T	A479D	0.976
19:49889907:C:A	W489C	0.974
19:49889907:C:G	W489C	0.974
19:49889893:A:T	V494D	0.973
19:49890578:A:G	W266R	0.973

dbSNP variants (sampled 300 via entrez): RS1000113894 (19:49920160 G>A), RS1000119806 (19:49925428 C>A,G,T), RS1000191148 (19:49901357 C>T), RS1000193604 (19:49915036 G>A), RS1000204539 (19:49899276 T>A,C), RS1000325974 (19:49905230 A>G), RS1000335013 (19:49914457 A>C,G), RS1000359557 (19:49930602 C>G,T), RS1000464848 (19:49920506 C>G,T), RS1000717550 (19:49905240 C>CAA), RS1000791431 (19:49899808 G>A,T), RS1000808252 (19:49918079 T>C), RS1000886414 (19:49889207 G>C), RS1000892118 (19:49924276 A>G), RS1000913718 (19:49929422 C>T)

Disease associations

OMIM: gene MIM:609742 | disease phenotypes: MIM:271930

GenCC curated gene-disease

Mondo (2): infantile bilateral striatal necrosis (MONDO:0015518), familial infantile bilateral striatal necrosis (MONDO:0010080)

Orphanet (2): Infantile bilateral striatal necrosis (Orphanet:1576), Familial infantile bilateral striatal necrosis (Orphanet:225154)

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): CHEMBL5291590 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9523	IL4I1, NUP62		0.00	0

ChEMBL bioactivities

20 potent at pChembl≥5 of 20 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	EC50	0.5	nM	CHEMBL5427667
9.05	EC50	0.9	nM	CHEMBL5407852
9.05	EC50	0.9	nM	CHEMBL5407445
9.05	EC50	0.9	nM	CHEMBL5394491
9.00	EC50	1	nM	CHEMBL5275112
9.00	EC50	1	nM	CHEMBL5266457
9.00	EC50	1	nM	CHEMBL5270158
9.00	EC50	1	nM	CHEMBL5409610
9.00	EC50	1	nM	CHEMBL5428253
8.70	EC50	2	nM	CHEMBL5267902
8.70	EC50	2	nM	CHEMBL5286613
8.70	EC50	2	nM	CHEMBL5273782
8.70	EC50	2	nM	CHEMBL5281686
8.30	EC50	5	nM	CHEMBL5269844
8.22	EC50	6	nM	CHEMBL5277779
8.00	EC50	10	nM	CHEMBL5275211
7.70	EC50	20	nM	CHEMBL5265950
7.64	EC50	23	nM	CHEMBL5267809
7.64	EC50	23	nM	CHEMBL5290612
7.17	EC50	68	nM	CHEMBL5272632

PubChem BioAssay actives

20 with measured affinity, of 20 total; 20 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
3-(1-benzofuran-3-ylmethyl)-1H-quinolin-2-one	1968808: Inhibition of recombinant IL4I1 (unknown origin) assessed as reduction in H2O2 production preincubated for 4 hrs followed by Phe/Tyr/Trp addition measured after 120 mins by fluorescence based analysis	ec50	0.0005	uM
3-[(3-oxo-1,2-dihydroinden-5-yl)methyl]-1H-quinolin-2-one	1968808: Inhibition of recombinant IL4I1 (unknown origin) assessed as reduction in H2O2 production preincubated for 4 hrs followed by Phe/Tyr/Trp addition measured after 120 mins by fluorescence based analysis	ec50	0.0009	uM
6-[(2-oxo-1H-quinolin-3-yl)methyl]-3H-1,3-benzoxazol-2-one	1968808: Inhibition of recombinant IL4I1 (unknown origin) assessed as reduction in H2O2 production preincubated for 4 hrs followed by Phe/Tyr/Trp addition measured after 120 mins by fluorescence based analysis	ec50	0.0009	uM
3-[(3-acetylphenyl)methyl]-1H-quinolin-2-one	1968808: Inhibition of recombinant IL4I1 (unknown origin) assessed as reduction in H2O2 production preincubated for 4 hrs followed by Phe/Tyr/Trp addition measured after 120 mins by fluorescence based analysis	ec50	0.0009	uM
1-cyclobutyl-4-[(5-phenyl-1,2-oxazol-3-yl)methyl]pyrazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0010	uM
1-cyclopentyl-4-[(3-phenyl-1,2-oxazol-5-yl)methyl]pyrazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0010	uM
1-cyclopentyl-4-[[5-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl]methyl]pyrazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0010	uM
1-[4-[(2-oxo-1H-quinolin-3-yl)methyl]phenyl]cyclopropane-1-carbonitrile	1968808: Inhibition of recombinant IL4I1 (unknown origin) assessed as reduction in H2O2 production preincubated for 4 hrs followed by Phe/Tyr/Trp addition measured after 120 mins by fluorescence based analysis	ec50	0.0010	uM
8-chloro-6-[(2-oxo-1H-quinolin-3-yl)methyl]-4H-1,4-benzoxazin-3-one	1968808: Inhibition of recombinant IL4I1 (unknown origin) assessed as reduction in H2O2 production preincubated for 4 hrs followed by Phe/Tyr/Trp addition measured after 120 mins by fluorescence based analysis	ec50	0.0010	uM
1-(1-bicyclo[1.1.1]pentanyl)-4-[[5-(3-fluorophenyl)-1,2-oxazol-3-yl]methyl]pyrazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0020	uM
1-cyclopentyl-4-[(3-phenyl-1,2-oxazol-5-yl)methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0020	uM
1-(3-phenylcyclobutyl)-4-[(5-phenyl-1,3,4-thiadiazol-2-yl)methyl]pyrazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0020	uM
1-cyclobutyl-4-[[6-(2-fluorophenyl)-3-pyridinyl]methyl]pyrazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0020	uM
1-cyclobutyl-4-[[5-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl]methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0050	uM
1-cyclopentyl-4-[[6-(3-fluorophenyl)pyridazin-3-yl]methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0060	uM
1-cyclobutyl-4-[[6-(2-fluorophenyl)pyridazin-3-yl]methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0100	uM
1-cyclobutyl-4-[1-(5-phenylpyrazin-2-yl)ethyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0200	uM
1-[(1S,5R)-3-bicyclo[3.1.0]hexanyl]-4-[[6-(1,3-thiazol-2-yl)pyridazin-3-yl]methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0230	uM
1-(1-bicyclo[1.1.1]pentanyl)-4-[(6-phenylpyridazin-3-yl)methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0230	uM
1-(oxolan-3-yl)-4-[(5-phenylpyrimidin-2-yl)methyl]piperazine-2,3-dione	1940705: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay	ec50	0.0680	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
bismuth tripotassium dicitrate	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	affects expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
pentanal	increases expression	1
gadodiamide	increases expression	1
abrine	increases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Aldehydes	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methapyrilene	increases methylation	1
Naled	affects expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Valproic Acid	increases methylation	1
Asbestos, Crocidolite	affects expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	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
CHEMBL5244199	Binding	Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish p	Inhibitors of Interleukin 4 Induced Protein 1 (IL4I1) as Potential Treatment for Cancer. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0YK	Ubigene MDA-MB-231 IL4I1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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