IL18BP

Summary

IL18BP (interleukin 18 binding protein, HGNC:5987) is a protein-coding gene on chromosome 11q13.4, encoding Interleukin-18-binding protein (O95998). Isoform A binds to IL-18 and inhibits its activity.

The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn’s disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 10068 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hepatitis, fulminant viral, susceptibility to (Limited, GenCC)
• Clinical variants (ClinVar): 309 total
• Phenotypes (HPO): 13
• MANE Select transcript: NM_001039660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5987
Approved symbol	IL18BP
Name	interleukin 18 binding protein
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	IL18BPa
Ensembl gene	ENSG00000137496
Ensembl biotype	protein_coding
OMIM	604113
Entrez	10068

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 21 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000337131, ENST00000343898, ENST00000393703, ENST00000393705, ENST00000393707, ENST00000404792, ENST00000414358, ENST00000497194, ENST00000525932, ENST00000531053, ENST00000531777, ENST00000534583, ENST00000620017, ENST00000698837, ENST00000698838, ENST00000698839, ENST00000698840, ENST00000698841, ENST00000905061, ENST00000905062, ENST00000905063, ENST00000905064, ENST00000905065, ENST00000905066, ENST00000905067, ENST00000905068, ENST00000948767, ENST00000948768, ENST00000948769, ENST00000948770

RefSeq mRNA: 7 — MANE Select: NM_001039660 NM_001039659, NM_001039660, NM_001145055, NM_001145057, NM_005699, NM_173042, NM_173044

CCDS: CCDS44666, CCDS8205, CCDS8206, CCDS8207

Canonical transcript exons

ENST00000393703 — 6 exons

Exon	Start	End
ENSE00000927482	72000351	72000557
ENSE00000927484	72001201	72001324
ENSE00001272430	71999927	72000012
ENSE00001295194	72001405	72001552
ENSE00001690249	72001784	72002804
ENSE00002145873	71998909	71999019

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 93.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5608 / max 686.2426, expressed in 1020 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115701	14.5032	582
115702	2.0919	342
115708	1.5520	469
115710	0.5731	236
115707	0.4456	199
115709	0.3247	125
115700	0.3186	123
115703	0.2651	118
115705	0.1835	27
115706	0.1600	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	93.26	gold quality
upper lobe of left lung	UBERON:0008952	90.14	gold quality
granulocyte	CL:0000094	89.80	gold quality
upper lobe of lung	UBERON:0008948	88.71	gold quality
ileal mucosa	UBERON:0000331	88.60	gold quality
apex of heart	UBERON:0002098	88.53	gold quality
metanephros cortex	UBERON:0010533	88.51	gold quality
lymph node	UBERON:0000029	87.50	gold quality
right adrenal gland	UBERON:0001233	87.24	gold quality
left adrenal gland cortex	UBERON:0035825	86.43	gold quality
left adrenal gland	UBERON:0001234	86.27	gold quality
right lung	UBERON:0002167	86.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.50	gold quality
right adrenal gland cortex	UBERON:0035827	85.28	gold quality
vermiform appendix	UBERON:0001154	85.21	gold quality
adrenal cortex	UBERON:0001235	85.04	gold quality
right lobe of thyroid gland	UBERON:0001119	84.41	gold quality
right ovary	UBERON:0002118	84.33	gold quality
mucosa of stomach	UBERON:0001199	84.31	gold quality
smooth muscle tissue	UBERON:0001135	84.15	gold quality
adrenal gland	UBERON:0002369	84.15	gold quality
omental fat pad	UBERON:0010414	83.76	gold quality
left coronary artery	UBERON:0001626	83.75	gold quality
peritoneum	UBERON:0002358	83.72	gold quality
rectum	UBERON:0001052	83.67	gold quality
small intestine	UBERON:0002108	83.67	gold quality
leukocyte	CL:0000738	83.51	gold quality
right coronary artery	UBERON:0001625	83.47	gold quality
left lobe of thyroid gland	UBERON:0001120	83.41	gold quality
body of uterus	UBERON:0009853	83.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, CREB1, IRF1, STAT1

miRNA regulators (miRDB)

54 targeting IL18BP, 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-12118	100.00	65.88	1270
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6744-5P	99.93	66.82	748
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-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-6770-5P	98.97	66.76	1853

Literature-anchored findings (GeneRIF, showing 40)

• trancriptional activation and release of IL-18 binding protein in response to IFN-gamma (PMID:11739524)
• IL-18BP messenger transcript and protein are significantly increased in surgically resected specimens from active Crohn’s disease compared with control patients, correlating with an up-regulation of IL-18. (PMID:11907126)
• after binding to IL-18BP, IL-1F7b forms a complex with IL-18Rbeta, depriving the beta-chain of forming a functional receptor complex with IL-18Ralpha and thus inhibiting IL-18 activity (PMID:12381835)
• IRF-1-CEBPbeta complex activate the promoter of IL-18 binding protein. (PMID:12482935)
• Administration of recombinant human IL-18BP not only reduces symptoms of murine contact hypersensitivity (CHS) during the elicitation phase but also significantly decreases inflammation in mice that had previously undergone CHS without treatment. (PMID:12874202)
• High endogenous levels of IL-18BP in trangenic mice effectively neutralize IL-18 and are protective in response to different inflammatory stimuli. (PMID:12960225)
• production of IL-18BP in response to IL-12 and IL-18 was regulated differently in blood and synovial cells. (PMID:15188356)
• IL-18 levels, which are determined in part by variation in IL18/IL18BP, play a role in coronary heart disease development and postsurgery outcome. (PMID:17951325)
• Despite the elevated IL-18BP levels during active disease, free IL-18 remained higher than in the inactive disease stages, suggesting a potential benefit of administration of exogenous IL-18BP as a therapeutic approach for active Wegener’s granulomatosis. (PMID:18594952)
• Altogether, data presented herein indicate that direct action of STAT1 on the IL-18BP promoter at the proximal GAS element is key to IL-18BP expression by IFN-gamma-stimulated DLD-1 colon carcinoma cells (PMID:19046253)
• Endometrial interleukin-18 binding protein mRNA expression may possibly be responsible for the pathologic process of adenomyosis. (PMID:19394601)
• High circulating levels in patients with active Systemic Lupus Erythematosus (PMID:19699611)
• Suggest that an early rise in IL-18 levels may play a role in reverse remodeling process following aortic valve replacement. (PMID:19961286)
• Since IL-18 plays a major role in perpetuating hemophagocytosis, the failure of IFNgamma to induce IL-18BP may constitute a fundamental pathogenetic mechanism (PMID:20072626)
• lupus nephritis patients present lower IL-18BP mRNA expression and higher serum levels of IL-18 than those in normal controls (PMID:20140691)
• In lines of intestinal epithelial cells from inflammatory bowel disease patients, interferon-gamma selectively up-regulated IL-18 binding protein. (PMID:21078084)
• increased levels of both IL-18 and its natural inhibitor IL-18BP, characterise SLE (PMID:21126942)
• IL-18/IL-18BP imbalance plays an important role in pathogenesis of primary immune thrombocytopenia. (PMID:21418867)
• In T2DM patients, 18 BP began to increase after IL-18 increased and reached a threshold, in which case kidney dysfunction would have developed. (PMID:21440322)
• High IL-18 BP levels indicate the severity of existing glomerular injury in systemic lupus erythematosus. (PMID:21656327)
• Imbalance between IL-18 and IL-18BP may play an important role in pathogenesis of idiopathic thrombocytopenic purpura. (PMID:21867627)
• The balance between interleukin-18 (IL-18) and its endogenous antagonist, IL-18 binding protein (IL-18BP), was evaluated in children with Henoch-Schonlein purpura. (PMID:22289535)
• Due to highly significant increases in circulating IL-18BP in schizophrenia compared to controls, the levels of free IL-18 are not significantly different between schizophrenic groups. (PMID:22913567)
• Data suggest that the imbalance of IL-18/IL-18BP might play an important role in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA) and it might go hand-in-hand with the severity of SJIA. (PMID:23419721)
• these data indicate that IL-18BP, which is produced in EOC in response to microenvironmental factors, may inhibit endogenous or exogenous IL-18 activity (PMID:23873689)
• HPV16 E7 oncoprotein increases production of the IL18BP in keratinocytes. (PMID:24478434)
• IL-18, IL-18BP, and IL-18R may have roles in the pathogenesis of epithelial ovarian carcinoma (PMID:24963217)
• The natural IL-18 inhibitor IL-18BP further regulates IL-18 activity in the extracellular environment. Review. (PMID:25548255)
• imbalance of IL-18/IL-18BP ratio in IgA nephropathy especially in patients with arteriolar lesions (PMID:25807634)
• the inhibition of IL-18 signaling by IL-18BPa may be involved in the development of pulmonary vascular involvement leading to pulmonary hypertension and modulate the systemic inflammation in systemic sclerosis (PMID:26777734)
• an imbalance in the production of IL-18 and its antagonist (an increase in the production of IL-18 with a decrease, no increase or an insufficient increase in the production of IL-18BP) has been described in many chronic inflammatory diseases in humans. (PMID:26898120)
• these results were corroborated in female osteoporotic subjects where decreased serum IL-18BP levels and enhanced serum IL-18 levels were observed. Our study forms a strong basis for using humanized IL-18BP towards the treatment of postmenopausal osteoporosis. (PMID:27649785)
• The maintenance of normal production of IL-18BP may contribute, at least in part, to the ability ofLong Term Non-Progressors to delay AIDS progression. (PMID:27863336)
• Platelets also contain the IL-18 antagonist, the IL-18-Binding Protein (IL-18BP); however, it is not synthesized in them de novo, is present in pre-made form and is released irrespective of platelet activation. (PMID:27914933)
• The serum levels of IL-37, which were correlated with antibody production and the serum levels of total IL-18 and IL-18BP, were elevated in the patients with primary Sjogren’s syndrome. (PMID:28057714)
• IL-18, IL-18R and IL-18BP expression in eosinophil are involved in the inflammatory reaction of asthma. (PMID:28395725)
• asthma is very likely to be determined by balance of IL-18/IL-18BP/IL-18R expression in inflammatory cells. (PMID:28922563)
• epigenetic silencing by single CpG methylation determines differential IL18BP inducibility in monocytic versus epithelial cells. T (PMID:29409936)
• a large proportion blood basophils from patients with asthma express IL-18 and IL-18BP. mast cells and basophils are implicated in the pathogenesis of asthma via an IL-18-related mechanism. (PMID:29505668)
• Level of interleukin-18 binding protein is significantly different in patients with anaphylaxis than urticaria. (PMID:31837215)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il18bp	ENSMUSG00000070427
rattus_norvegicus	Il18bp	ENSRNOG00000020150

Protein

Protein identifiers

Interleukin-18-binding protein — O95998 (reviewed: O95998)

Alternative names: Tadekinig-alfa

All UniProt accessions (3): O95998, A0A8V8TP32, G3V1C5

UniProt curated annotations — full annotation on UniProt →

Function. Isoform A binds to IL-18 and inhibits its activity. Functions as an inhibitor of the early TH1 cytokine response.

Subcellular location. Secreted.

Tissue specificity. Strongly expressed in heart, lung, placenta and spleen.

Post-translational modifications. N- and O-glycosylated. O-glycosylated with core 1-like and core 2-like glycans. O-glycan heterogeneity at Ser-53: HexHexNAc (major) and Hex2HexNAc2 (minor). N-glycan heterogeneity at Asn-103: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (major) and Hex6HexNAc5 (minor); N-glycan at Asn-147: dHex1Hex5HexNAc4.

Disease relevance. Hepatitis, fulminant viral (FVH) [MIM:618549] An autosomal recessive form of fulminant viral hepatitis, a disease that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses. FVH is characterized by severe liver destruction in the absence of a preexisting liver disorder, leading to encephalopathy within 8 weeks of the onset of the first symptoms. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
O95998-2	A, IL-18BPA	yes
O95998-3	B, IL-18BPB
O95998-4	D, IL-18BPD

RefSeq proteins (7): NP_001034748, NP_001034749, NP_001138527, NP_001138529, NP_005690, NP_766630, NP_766632 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR039681	IL18BP	Family
IPR055139	IL18BP-like_dom	Domain

Pfam: PF22009

UniProt features (27 total): strand 9, glycosylation site 5, splice variant 4, helix 3, sequence variant 2, signal peptide 1, chain 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7AL7	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95998-F1	79.53	0.54

Functional residue map

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

Disulfide bonds (1): 86–150

Glycosylation sites (5): 53, 79, 94, 103, 147

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9008059	Interleukin-37 signaling
R-HSA-9012546	Interleukin-18 signaling

MSigDB gene sets: 243 (showing top): GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr11q13, AGGCACT_MIR5153P, IRF7_01, GOBP_REGULATION_OF_IMMUNE_RESPONSE, RICKMAN_METASTASIS_DN, GOBP_T_HELPER_1_TYPE_IMMUNE_RESPONSE, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_CELLULAR_RESPONSE_TO_HYDROGEN_PEROXIDE, IRF1_Q6

GO Biological Process (4): response to lipopolysaccharide (GO:0032496), T-helper 1 type immune response (GO:0042088), cellular response to hydrogen peroxide (GO:0070301), cellular response to tumor necrosis factor (GO:0071356)

GO Molecular Function (2): interleukin-18 binding (GO:0042007), receptor antagonist activity (GO:0048019)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-1 family signaling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
cytokine binding	1
signaling receptor binding	1
signaling receptor inhibitor activity	1
extracellular vesicle	1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL18BP	IL18	Q14116	998
IL18BP	IL37	Q9NZH6	906
IL18BP	IL18R1	Q13478	850
IL18BP	IL18RAP	O95256	783
IL18BP	IL33	O95760	653
IL18BP	VCAM1	P19320	626
IL18BP	IL1B	P01584	590
IL18BP	IL1A	P01583	580
IL18BP	IFNG	P01579	578
IL18BP	CASP1	P29466	574
IL18BP	IL1R2	P27930	546
IL18BP	CXCL8	P10145	544
IL18BP	IFNA13	P01562	523
IL18BP	PRTN3	P15637	507
IL18BP	IL1R1	P14778	507

IntAct

9 interactions, top by confidence:

A	B	Type	Score
KIR3DL3	IL18BP	psi-mi:“MI:0915”(physical association)	0.400
IL6R	IL18BP	psi-mi:“MI:0915”(physical association)	0.400
LILRA3	IL18BP	psi-mi:“MI:0915”(physical association)	0.400
MAG	IL18BP	psi-mi:“MI:0915”(physical association)	0.400
IL18BP		psi-mi:“MI:0915”(physical association)	0.000
pepP	IL18BP	psi-mi:“MI:0915”(physical association)	0.000
IL18BP	groEL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): IL18BP (Reconstituted Complex), IL18BP (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GW64, A0A5F4BST2, A0PJX4, A8MVS5, A8MWV9, B0FP48, E5RIL1, E9PGG2, O14836, O60320, O95998, P09564, Q01113, Q01114, Q13477, Q2KI80, Q2T9R2, Q3TS39, Q3UPR0, Q3URD2, Q4V9L6, Q5FVJ4, Q5M869, Q6A044, Q6UWJ8, Q75VT8, Q864V4, Q8BRJ3, Q8BX43, Q8C503, Q8IVY1, Q8K5A9, Q8N112, Q8NC24, Q8NDY8, Q8QZT4, Q8R138, Q969Z4, Q9BUF7, Q9CQM1

Diamond homologs: O95998, Q9Z0M9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	213
Likely benign	63
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

2074 predictions. Top by Δscore:

Variant	Effect	Δscore
11:72000504:C:G	donor_gain	1.0000
11:72001197:CTAG:C	acceptor_loss	1.0000
11:72001198:TAGAT:T	acceptor_loss	1.0000
11:72001199:A:AG	acceptor_gain	1.0000
11:72001199:AGAT:A	acceptor_gain	1.0000
11:72001200:G:GA	acceptor_loss	1.0000
11:72001200:G:GG	acceptor_gain	1.0000
11:72001200:GATG:G	acceptor_gain	1.0000
11:72001315:G:T	donor_gain	1.0000
11:72001322:CAGG:C	donor_loss	1.0000
11:72001324:GGTG:G	donor_loss	1.0000
11:72001326:T:G	donor_loss	1.0000
11:72001397:C:A	acceptor_gain	1.0000
11:72001401:CCAGC:C	acceptor_loss	1.0000
11:72001403:A:AG	acceptor_gain	1.0000
11:72001403:AGCC:A	acceptor_gain	1.0000
11:72001403:AGCCG:A	acceptor_gain	1.0000
11:72001404:G:GC	acceptor_gain	1.0000
11:72001404:GC:G	acceptor_gain	1.0000
11:72001404:GCC:G	acceptor_gain	1.0000
11:72001404:GCCG:G	acceptor_gain	1.0000
11:72001404:GCCGG:G	acceptor_gain	1.0000
11:72003890:G:A	donor_gain	1.0000
11:72004098:GCC:G	acceptor_loss	1.0000
11:72004099:CCT:C	acceptor_loss	1.0000
11:72004100:C:CC	acceptor_gain	1.0000
11:72004219:CCTCA:C	donor_loss	1.0000
11:72004220:CTCAC:C	donor_loss	1.0000
11:72004221:TCAC:T	donor_loss	1.0000
11:72004222:CAC:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000120970 (11:72001986 C>T), RS1000716402 (11:72000813 T>C), RS1000718796 (11:72005520 G>A), RS1000969227 (11:72002719 G>A), RS1001266929 (11:71998995 C>G), RS1001373065 (11:71997103 G>A), RS1001584822 (11:72007116 G>A,C), RS1002279428 (11:72005870 G>A,T), RS1002894249 (11:72001149 G>A,T), RS1002999983 (11:72006018 C>G,T), RS1003359364 (11:71999478 A>C), RS1003609960 (11:71997898 C>T), RS1003637992 (11:72002189 C>T), RS1003825495 (11:72002384 C>CCTAT), RS1003849711 (11:72005100 A>T)

Disease associations

OMIM: gene MIM:604113 | disease phenotypes: MIM:618549, MIM:612376

GenCC curated gene-disease

Disease	Classification	Inheritance
hepatitis, fulminant viral, susceptibility to	Limited	Unknown

Mondo (2): hepatitis, fulminant viral, susceptibility to (MONDO:0032809), acute promyelocytic leukemia (MONDO:0012883)

Orphanet (1): Acute promyelocytic leukemia (Orphanet:520)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000225	Gingival bleeding
HP:0000872	Hashimoto thyroiditis
HP:0000952	Jaundice
HP:0001259	Coma
HP:0001399	Hepatic failure
HP:0002018	Nausea
HP:0002240	Hepatomegaly
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0004396	Poor appetite
HP:0004787	Fulminant hepatitis
HP:0012378	Fatigue
HP:0100651	Type I diabetes mellitus

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015473	Leukemia, Promyelocytic, Acute	C04.557.337.539.275.700; C15.378.508.539.275.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-methylcholine	affects expression	1
hispidulin	affects cotreatment, decreases reaction, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases reaction, increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Nickel	increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Gold Compounds	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00196768	PHASE4	UNKNOWN	Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic
NCT00408278	PHASE4	COMPLETED	Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005)
NCT00465933	PHASE4	COMPLETED	Treatment of Acute Promyelocytic Leukemia With All-Trans Retinoic Acid (ATRA) and Idarubicin (AIDA)
NCT00504764	PHASE4	COMPLETED	Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
NCT01987297	PHASE4	UNKNOWN	Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL
NCT02020161	PHASE4	UNKNOWN	Clinical Guidelines for APL Treatment
NCT01226303	PHASE3	UNKNOWN	Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia
NCT02688140	PHASE3	COMPLETED	Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia
NCT02899169	PHASE3	UNKNOWN	Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF)
NCT04175587	PHASE3	UNKNOWN	Randomized,International Multi-center Clinical Trial of RIF Plus RA for Non-high-risk APL
NCT07296445	PHASE3	NOT_YET_RECRUITING	A Trial to Investigate Whether Oral Arsenic Trioxide Is Similar to Intravenous Arsenic Trioxide in Pharmacokinetics, Safety, and Efficacy (LATITUDE/SDKARS-301)
NCT07503730	PHASE3	RECRUITING	Early Use of Realgar-Indigo Naturalis Formula (RIF) Combined With All-trans Retinoic Acid (ATRA) for Treating Acute Promyelocytic Leukemia (APL).
NCT07504458	PHASE3	RECRUITING	Pivotal Open-label Phase 3 Clinical Study of QTX-2101 in Adult Patients With Acute Promyelocytic Leukemia
NCT00413166	PHASE2	COMPLETED	All-trans Retinoic Acid, and Arsenic +/- Idarubicin
NCT00520208	PHASE2	COMPLETED	Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL
NCT00670150	PHASE2	WITHDRAWN	New Retinoid Agent Combined With Arsenic Trioxide for Untreated Acute Promyelocytic Leukemia
NCT00675870	PHASE2	UNKNOWN	Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia
NCT00907582	PHASE2	TERMINATED	ASCT for Relapsed APL After Molecular Remission
NCT01064570	PHASE2	UNKNOWN	AIDA 2000 Guidelines
NCT01253070	PHASE2	COMPLETED	Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
NCT01404949	PHASE2	COMPLETED	Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
NCT01409161	PHASE2	RECRUITING	Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia
NCT03624270	PHASE2	UNKNOWN	Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia
NCT04687176	PHASE2	RECRUITING	Frontline Oral Arsenic Trioxide for APL
NCT04793919	PHASE2	RECRUITING	Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia
NCT05881265	PHASE2	RECRUITING	Treatment of Chidamide and Venetoclax for Retinoic Acid and Arsenic Resistant Acute Promyelocytic Leukemia
NCT06982274	PHASE2	RECRUITING	Oral Arsenic With ATRA for Newly Diagnosed Patients With Acute Promyelocytic Leukemia
NCT00852709	PHASE1	TERMINATED	Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias
NCT00985530	PHASE1	TERMINATED	Tamibarotene and Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia
NCT01902329	PHASE1	COMPLETED	A Safety Study of SGN-CD33A in AML Patients
NCT02086773	PHASE1	COMPLETED	Red Cell Transfusion Goals in Patients With Acute Leukemias
NCT02390635	PHASE1	RECRUITING	PET/MRI, 18F-FDG PET/CT and Whole Body MRI in Finding Extramedullary Myeloid Leukemia in Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT04996030	PHASE1	SUSPENDED	A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia
NCT06882031	PHASE1	COMPLETED	Evaluate the Pharmacokinetics of Oral Arsenic Trioxide Solution Under Fasting and Fed Conditions, to Compare Intravenous Arsenic Trioxide, in Acute Promyelocytic Leukemia
NCT00517712	PHASE2/PHASE3	UNKNOWN	Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia
NCT06544109	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Venetoclax for Prevention of Differentiation Syndrom in Acute Promyelocytic Leukemia Patients
NCT07597941	PHASE2/PHASE3	NOT_YET_RECRUITING	Lisaftoclax for Prevention of Differentiation Syndrom in Acute Promyelocytic Leukemia Patients
NCT05497310	PHASE1/PHASE2	UNKNOWN	Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL
NCT00003861	Not specified	ACTIVE_NOT_RECRUITING	Diagnostic Study of Patients With Acute Lymphoblastic Leukemia or Acute Promyelocytic Leukemia
NCT01463410	Not specified	TERMINATED	Accuracy Testing of the Chromosomal Aberration and Gene Mutation Markers of the AMLProfiler