IL1B Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human IL1B — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene IL1B, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene IL1B, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene IL1B protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene IL1B protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene IL1B, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene IL1B, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene IL1B, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene IL1B protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene IL1B, summarize transcription factor regulatory data. If IL1B is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate IL1B — names with evidence type (ChIP-seq / predicted / experimentally validated) If IL1B is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene IL1B protein as a drug target, summarize pharmacology data. If IL1B is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If IL1B is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene IL1B, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene IL1B, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in IL1B: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
IL1B (interleukin-1 beta, HGNC:5992) encodes a master pro-inflammatory cytokine that sits at the center of innate immune signaling, making it one of the most clinically actionable targets in inflammation biology. Located on chromosome 2 (GRCh38: 112,829,751–112,836,816), it produces a well-characterized protein (UniProt P01584) with 64 experimental PDB structures and an extensive interaction network exceeding 8,500 documented partners, dominated by cytokine family members and inflammasome components (NLRP3, CASP1, GSDMD). Expression is highest in myeloid cells — granulocytes and monocytes — and is strongly upregulated in inflammatory contexts across 228 tissues. Three FDA-approved drugs directly target this pathway (anakinra, canakinumab, rilonacept), with hundreds of ongoing clinical trials. GWAS links the locus to allergic disease, dysmenorrhea, and gestational traits, while no clearly pathogenic Mendelian variants have been established in ClinVar.
Gene identifiers
IL1B — interleukin 1 beta
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:5992 |
| Approved symbol | IL1B |
| Ensembl gene ID | ENSG00000125538 |
| NCBI Entrez Gene ID | 3553 |
| OMIM locus ID | 147720 |
| Genomic location (GRCh38) | |
| Chromosome | 2 |
| Start position | 112,829,751 |
| End position | 112,836,816 |
| Strand | − (minus) |
Transcript identifiers
Ensembl Transcripts (8 total)
| ENST ID | Biotype |
|---|---|
| ENST00000263341 | protein_coding |
| ENST00000416750 | protein_coding |
| ENST00000418817 | protein_coding |
| ENST00000432018 | protein_coding |
| ENST00000477398 | retained_intron |
| ENST00000487639 | retained_intron |
| ENST00000491056 | protein_coding_CDS_not_defined |
| ENST00000496280 | retained_intron |
Total: 8 transcripts
RefSeq mRNA Accessions
| NM ID | Status | MANE Select |
|---|---|---|
| NM_000576 | REVIEWED | ✓ |
| NM_008361 | REVIEWED | |
| NM_031512 | PROVISIONAL | |
| NM_212844 | VALIDATED |
CCDS ID
| CCDS ID |
|---|
| CCDS2102 |
Canonical/MANE Select Transcript Exons
Transcript: ENST00000263341 (RefSeq: NM_000576)
Total exons: 7
| ENSE ID | Start | End | Strand | Chromosome |
|---|---|---|---|---|
| ENSE00000856835 | 112829751 | 112830573 | - | 2 |
| ENSE00003615183 | 112831292 | 112831422 | - | 2 |
| ENSE00003582426 | 112832662 | 112832826 | - | 2 |
| ENSE00003506405 | 112833374 | 112833575 | - | 2 |
| ENSE00003508205 | 112836183 | 112836244 | - | 2 |
| ENSE00001000625 | 112836708 | 112836779 | - | 2 |
| ENSE00003647827 | 112835566 | 112835617 | - | 2 |
Protein identifiers
UniProt Accessions
| Accession | Status | Protein Name |
|---|---|---|
| P01584 | Reviewed (Canonical) | Interleukin-1 beta |
| C9JSC2 | Unreviewed | - |
| C9JVK0 | Unreviewed | - |
| C9JWV2 | Unreviewed | - |
RefSeq Protein (NP_) Accessions
| Accession | Status | MANE Select |
|---|---|---|
| NP_000567 | REVIEWED | ✓ |
| NP_032387 | REVIEWED | - |
| NP_113700 | PROVISIONAL | - |
| NP_998009 | VALIDATED | - |
Protein Domains and Families
InterPro
| ID | Short Name | Type | Full Name |
|---|---|---|---|
| IPR000975 | IL-1_fam | Family | Interleukin-1 family |
| IPR003502 | IL-1_propep | Domain | Interleukin-1 propeptide |
| IPR008996 | IL1/FGF | Homologous_superfamily | Cytokine IL1/FGF |
| IPR020877 | IL-1_CS | Conserved_site | Interleukin-1 conserved site |
Pfam
| ID |
|---|
| PF00340 |
| PF02394 |
SMART
| ID |
|---|
| SM00125 |
Superfamily (SUPFAM)
| ID |
|---|
| SSF50353 |
Antibody Resources
| Name | Type | Isotype | Status | Target(s) |
|---|---|---|---|---|
| CANAKINUMAB | Whole mAb | G1 | Active | IL1B |
| GEVOKIZUMAB | Whole mAb | G2 | Active | IL1B |
| FIRSEKIBART | Whole mAb | G4 | TBC | IL1B |
| ARUMAKIMIG | Bispecific mAb | G1;G1 | TBC | IL18;IL1B |
| LUTIKIZUMAB | Bispecific Dual Variable Domain IG | G1;G1 | Discontinued | IL1A;IL1B |
Structure
Experimental Structures: PDB
Total: 64 PDB entries
X-ray Diffraction (61 structures)
| PDB ID | Resolution (Å) |
|---|---|
| 1HIB | 2.4 |
| 1I1B | 2.0 |
| 1IOB | 2.0 |
| 1ITB | 2.5 |
| 1L2H | 1.54 |
| 1S0L | 2.34 |
| 1T4Q | 2.1 |
| 1TOO | 2.1 |
| 1TP0 | 2.2 |
| 1TWE | 2.1 |
| 1TWM | 2.26 |
| 21BI | 2.0 |
| 2I1B | 2.0 |
| 2NVH | 1.53 |
| 31BI | 2.0 |
| 3LTQ | 2.1 |
| 3O4O | 3.3 |
| 3POK | 1.7 |
| 41BI | 2.9 |
| 4DEP | 3.1 |
| 4G6J | 2.03 |
| 4G6M | 1.81 |
| 4GAF | 2.15 |
| 4GAI | 1.49 |
| 4I1B | 2.0 |
| 5BVP | 2.2 |
| 5I1B | 2.1 |
| 5MVZ | 2.15 |
| 5R7W | 1.27 |
| 5R85 | 1.44 |
| 5R86 | 1.5 |
| 5R87 | 1.47 |
| 5R88 | 1.48 |
| 5R89 | 1.65 |
| 5R8A | 1.47 |
| 5R8B | 1.49 |
| 5R8C | 1.54 |
| 5R8D | 1.47 |
| 5R8E | 1.35 |
| 5R8F | 1.41 |
| 5R8G | 1.43 |
| 5R8H | 1.5 |
| 5R8I | 1.47 |
| 5R8J | 1.62 |
| 5R8K | 1.47 |
| 5R8L | 1.56 |
| 5R8M | 1.39 |
| 5R8N | 1.48 |
| 5R8O | 1.42 |
| 5R8P | 1.53 |
| 5R8Q | 1.23 |
| 6Y8I | 1.46 |
| 6Y8M | 1.9 |
| 7CHY | 2.65 |
| 7CHZ | 2.5 |
| 7Z4T | 3.3 |
| 8C3U | 1.945 |
| 8RYK | 1.8 |
| 8RYS | 1.16 |
| 8RZB | 1.836 |
| 9ILB | 2.28 |
Solution NMR (3 structures)
| PDB ID |
|---|
| 2KH2 |
| 6I1B |
| 7I1B |
Predicted Structures: AlphaFold
| Model ID | pLDDT (global metric) | Residues with very high confidence (pLDDT >90) |
|---|---|---|
| P01584 | 76.24 | 49% |
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 16176 | Il1b |
| Rat (Rattus norvegicus) | 24494 | Il1b |
| Zebrafish (Danio rerio) | 405770 | il1b |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Summary
| Classification | Count |
|---|---|
| Pathogenic | 0 |
| Likely Pathogenic | 0 |
| Uncertain Significance | ~10 |
| Likely Benign | ~2 |
| Benign | ~1 |
| Risk Factor / Association / Affects | ~28 |
| Total | 41 |
Top ClinVar Pathogenic/Likely Pathogenic Variants
No variants classified as Pathogenic or Likely Pathogenic are currently present in ClinVar for IL1B. Most variants fall into Uncertain Significance or disease association categories.
Notable variants by classification:
| Variant ID | HGVS | Condition | Classification |
|---|---|---|---|
| 869137 | c.315C>T (p.Phe105=) | Endometriosis, Antisynthetase syndrome | Benign; Affects |
| 14671 | g.112836810G>A | Gastric cancer (H. pylori) | Risk Factor |
| 4274893 | c.43T>C (p.Tyr15His) | AllHighlyPenetrant | Uncertain Significance |
| 1049443 | c.28G>A (p.Glu10Lys) | None provided | Uncertain Significance |
| 4502973 | c.597+1G>A (splice) | Ovarian serous cystadenocarcinoma | No classification |
| 4502972 | c.597+5G>C (splice) | Head/neck squamous cell carcinoma | No classification |
| 4274894 | c.419A>G (p.Tyr140Cys) | AllHighlyPenetrant | Likely Benign |
AlphaMissense Predictions
Total variants: 185
Likely Pathogenic: 100+ (first batch shown; additional pages available)
Top 30 Likely Pathogenic Variants (by am_pathogenicity score):
| Protein Variant | am_pathogenicity | Position | Consequence |
|---|---|---|---|
| F262S | 0.998 | 262 | Severe aromatic change |
| F262L | 0.996 | 262 | Aromatic to hydrophobic |
| F262C | 0.996 | 262 | Aromatic to polar |
| F262I | 0.966 | 262 | Aromatic to hydrophobic |
| F262V | 0.973 | 262 | Aromatic to hydrophobic |
| L250P | 0.976 | 250 | Proline introduction |
| L250R | 0.971 | 250 | Charge reversal |
| L250Q | 0.971 | 250 | Charged change |
| V248D | 0.997 | 248 | Charge introduction |
| F249L | 0.990 | 249 | Aromatic to hydrophobic |
| W236R | 0.990 | 236 | Tryptophan loss |
| F249C | 0.848 | 249 | Aromatic to polar |
| G251E | 0.891 | 251 | Charge introduction |
| S239R | 0.996 | 239 | Charge introduction |
| Y237S | 0.974 | 237 | Aromatic loss |
| Y237D | 0.989 | 237 | Aromatic loss + charge |
| I238T | 0.996 | 238 | Hydrophobic to polar |
| I238S | 0.996 | 238 | Hydrophobic to polar |
| I238N | 0.997 | 238 | Hydrophobic to polar |
| T240I | 0.987 | 240 | Polar to hydrophobic |
| T240N | 0.960 | 240 | Polar change |
| S239N | 0.979 | 239 | Charge to polar |
| S239I | 0.981 | 239 | Charge to hydrophobic |
| P234H | 0.734 | 234 | Proline context change |
| D261H | 0.766 | 261 | Charge reversal |
| M264R | 0.771 | 264 | Charge introduction |
| M264K | 0.771 | 264 | Charge introduction |
| I259K | 0.748 | 259 | Charge introduction |
| T263P | 0.689 | 263 | Proline introduction |
| D258V | 0.674 | 258 | Charge loss |
Splice Predictions
No SpliceAI predictions available in biobtree for IL1B. Two candidate splice site variants identified in ClinVar:
- c.597+1G>A (canonical donor site +1) — likely damaging
- c.597+5G>C (donor site +5) — potentially damaging
Human IL1B shows predominantly uncertain/unknown clinical significance. AlphaMissense identifies concentrated pathogenic predictions in C-terminal region (residues 233–266), with high-confidence predictions for aromatic and hydrophobic substitutions, proline introductions, and charge reversals.
Pathways & Gene Ontology
Reactome Pathways
IL1B participates in 9 Reactome pathways:
| Pathway ID | Pathway Name | Disease |
|---|---|---|
| R-HSA-448706 | Interleukin-1 processing | No |
| R-HSA-5620971 | Pyroptosis | No |
| R-HSA-5660668 | CLEC7A/inflammasome pathway | No |
| R-HSA-6783783 | Interleukin-10 signaling | No |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | No |
| R-HSA-9020702 | Interleukin-1 signaling | No |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | Yes |
| R-HSA-9960519 | CASP4-mediated substrate cleavage | No |
| R-HSA-9960525 | CASP5-mediated substrate cleavage | No |
Gene Ontology Annotations
Total GO Terms: 107
Biological Process (94 terms)
TOP 20:
| GO ID | Term |
|---|---|
| GO:0001660 | fever generation |
| GO:0001819 | positive regulation of cytokine production |
| GO:0002711 | positive regulation of T cell mediated immunity |
| GO:0006915 | apoptotic process |
| GO:0006954 | inflammatory response |
| GO:0006955 | immune response |
| GO:0007165 | signal transduction |
| GO:0007254 | JNK cascade |
| GO:0007267 | cell-cell signaling |
| GO:0007566 | embryo implantation |
| GO:0008284 | positive regulation of cell population proliferation |
| GO:0008285 | negative regulation of cell population proliferation |
| GO:0009743 | response to carbohydrate |
| GO:0010573 | vascular endothelial growth factor production |
| GO:0010575 | positive regulation of vascular endothelial growth factor production |
| GO:0010628 | positive regulation of gene expression |
| GO:0010641 | positive regulation of platelet-derived growth factor receptor signaling pathway |
| GO:0010718 | positive regulation of epithelial to mesenchymal transition |
| GO:0010744 | positive regulation of macrophage derived foam cell differentiation |
| GO:0010829 | negative regulation of D-glucose transmembrane transport |
Molecular Function (6 terms)
| GO ID | Term |
|---|---|
| GO:0005125 | cytokine activity |
| GO:0005149 | interleukin-1 receptor binding |
| GO:0005178 | integrin binding |
| GO:0005515 | protein binding |
| GO:0019904 | protein domain specific binding |
| GO:0048018 | receptor ligand activity |
Cellular Component (7 terms)
| GO ID | Term |
|---|---|
| GO:0005576 | extracellular region |
| GO:0005615 | extracellular space |
| GO:0005737 | cytoplasm |
| GO:0005764 | lysosome |
| GO:0005829 | cytosol |
| GO:0030141 | secretory granule |
| GO:0031982 | vesicle |
Protein interactions & networks
Protein-Protein Interactions (PPIs)
Total interaction count (approximate):
- STRING: 8,488 interactions
- BioGRID: 60 interactions
- IntAct: 16 interactions
- Combined total: ~8,564 interactions
TOP 30 highest-confidence interacting proteins (STRING database):
| Rank | UniProt ID | Score | Notes |
|---|---|---|---|
| 1 | P01585 | 999 | IL1 alpha |
| 2 | P14778 | 999 | TNF-α related |
| 3 | P01579 | 998 | IL1 family |
| 4 | P05112 | 998 | IL1 family |
| 5 | P05113 | 998 | IL1 family |
| 6 | P78397 | 998 | IL1 signaling |
| 7 | P19438 | 997 | IL6 (cytokine) |
| 8 | Q9NPH3 | 997 | Immune regulation |
| 9 | P04141 | 996 | TNF superfamily |
| 10 | P27930 | 996 | Immune signaling |
| 11 | P01375 | 993 | TNF ligand |
| 12 | P09919 | 993 | IL4 (cytokine) |
| 13 | P05231 | 990 | IL3 (cytokine) |
| 14 | P29466 | 988 | IL12 (cytokine) |
| 15 | O00206 | 984 | Immune protein |
| 16 | P01583 | 983 | IL1 family |
| 17 | P22301 | 978 | TNF-related |
| 18 | P51617 | 978 | Signaling protein |
| 19 | P08700 | 976 | IL2 (cytokine) |
| 20 | P01023 | 975 | TNF-α (TNF) |
| 21 | Q9NR96 | 975 | Immune protein |
| 22 | P08887 | 974 | IL7 (cytokine) |
| 23 | Q14116 | 973 | Immune signaling |
| 24 | P10145 | 963 | IL6 (cytokine) |
| 25 | Q9Y4K3 | 963 | Immune protein |
| 26 | O60603 | 960 | Cytokine related |
| 27 | P19838 | 960 | Immune signaling |
| 28 | Q16552 | 960 | IL17 family |
| 29 | P09429 | 959 | IL5 (cytokine) |
| 30 | P50877 | 954 | TNF receptor |
Key BioGRID interactions (60 total, selected high-confidence):
- IL1R1 (Reconstituted Complex)
- NLRP3 (Inflammasome component - Affinity Capture-Western)
- CASP1/CASP8 (Caspase proteases - Affinity Capture-Western/MS)
- GSDMD (Gasdermin - Affinity Capture-Western)
- HSP90AA1 (Heat shock protein - Affinity Capture-Western)
- CDC37 (Chaperone - Affinity Capture-Western)
- IL18 (Related cytokine - Affinity Capture-MS)
- PDCD6IP/VPS28/VPS4B (ESCRT pathway - Affinity Capture-MS)
IntAct curated interactions (16 total, highest confidence):
- IL1RAP: 0.760 (physical association, multiple studies)
- IL1R1: 0.440 (direct interaction)
- CASP1: 0.440 (protein cleavage/processing)
- IKBKG: 0.400 (NF-κB pathway)
- MYC: 0.350 (gene regulation association)
- A2M: 0.270 (proximity/localization)
Protein Similarity
Structural/Embedding Similarity (ESM2 embeddings) - TOP 20:
| Rank | UniProt ID | Top Similarity Score | Avg Similarity | Description |
|---|---|---|---|---|
| 1 | P48090 | 1.0000 | 0.9916 | IL1 ortholog |
| 2 | P51493 | 1.0000 | 0.9916 | IL1 ortholog |
| 3 | Q2HZH0 | 1.0000 | 0.9918 | IL1 ortholog |
| 4 | Q6PUD2 | 1.0000 | 0.9918 | IL1 ortholog |
| 5 | P21621 | 0.9999 | 0.9920 | IL1 ortholog |
| 6 | P79340 | 0.9999 | 0.9904 | IL1 ortholog |
| 7 | Q2MH07 | 0.9999 | 0.9923 | IL1 ortholog |
| 8 | P09428 | 0.9999 | 0.9923 | IL1 ortholog |
| 9 | P08831 | 0.9998 | 0.9913 | IL1 ortholog |
| 10 | P46648 | 0.9998 | 0.9915 | IL1 ortholog |
| 11 | P79161 | 0.9998 | 0.9913 | IL1 ortholog |
| 12 | Q3HWU1 | 0.9998 | 0.9918 | IL1 ortholog |
| 13 | P51745 | 0.9997 | 0.9924 | IL1 ortholog |
| 14 | Q28579 | 0.9997 | 0.9905 | IL1 ortholog |
| 15 | A4UYK8 | 0.9996 | 0.9921 | IL1 ortholog |
| 16 | P01584 | 0.9996 | 0.9915 | Self (IL1B human) |
| 17 | Q865X7 | 0.9996 | 0.9918 | IL1 ortholog |
| 18 | Q28292 | 0.9992 | 0.9921 | IL1 ortholog |
| 19 | O46612 | 0.9992 | 0.9920 | IL1 ortholog |
| 20 | O46613 | 0.9992 | 0.9918 | IL1 ortholog |
Sequence Homology (DIAMOND) - TOP 20:
| Rank | UniProt ID | Sequence Identity | BitScore | Description |
|---|---|---|---|---|
| 1 | Q2HZH0 | 100.00% | 546.0 | IL1 ortholog (perfect match) |
| 2 | Q6PUD2 | 100.00% | 546.0 | IL1 ortholog (perfect match) |
| 3 | P48090 | 99.30% | 536.0 | IL1 ortholog |
| 4 | P79182 | 99.30% | 535.0 | IL1 ortholog |
| 5 | P51493 | 98.50% | 534.0 | IL1 ortholog |
| 6 | P09428 | 98.50% | 527.0 | IL1 ortholog |
| 7 | Q2MH07 | 98.50% | 528.0 | IL1 ortholog |
| 8 | P21621 | 98.50% | 519.0 | IL1 ortholog |
| 9 | P79162 | 98.50% | 520.0 | IL1 ortholog |
| 10 | P46648 | 97.40% | 527.0 | IL1 ortholog |
| 11 | Q6R2X3 | 95.20% | 525.0 | IL1 ortholog |
| 12 | P51745 | 94.00% | 502.0 | IL1 ortholog |
| 13 | P01584 | 91.10% | 494.0 | Self (IL1B human) |
| 14 | Q9QYY1 | 91.00% | 285.0 | IL1 related |
| 15 | Q9UBH0 | 91.00% | 288.0 | IL1 related |
| 16 | P10749 | 87.40% | 475.0 | IL1 family |
| 17 | Q63264 | 87.40% | 474.0 | IL1 family |
| 18 | A4UYK8 | 84.40% | 463.0 | IL1 family |
| 19 | P14628 | 74.30% | 399.0 | IL1 family |
| 20 | P26889 | 74.20% | 396.0 | IL1 family |
Summary: IL1B exhibits extensive interaction networks dominated by cytokine family members (IL1 family, TNF superfamily, IL6, IL12, IL4, IL2, IL7) and inflammasome signaling components (NLRP3, CASP1, CASP8, GSDMD). Similarity searches reveal orthologs across species with near-perfect sequence identity (up to 100%), reflecting strong conservation of this critical immunomodulatory protein.
Transcription factor regulatory data
IL1B is not a transcription factor. IL1B (interleukin 1 beta) is a cytokine—a protein-coding gene that encodes a pro-inflammatory signaling molecule, not a transcription factor that binds DNA. Therefore, no DNA binding motifs from JASPAR are applicable.
Upstream regulators
IL1B is regulated by 126 documented transcription factors via the collectri database (signal transduction and indirect regulatory mechanisms). Key upstream regulators with evidence:
Activators (High Confidence):
- NFKB pathway: NFKB, NFKB1, RELA, RELB, REL (ChIP-seq evidence, High confidence)
- IRF family: IRF1, IRF4, IRF8 (High confidence)
- CEBPB (High confidence)
- CREB1 (High confidence)
- EGR1 (High confidence)
- FOXO1 (High confidence)
- NFE2L2 (High confidence)
- SP1, SPI1 (High confidence)
- STAT1 (High confidence)
Repressors (High Confidence):
- NR3C1 (glucocorticoid receptor, High confidence)
- KLF4 (High confidence)
- HSF1 (High confidence)
- NFKBIA (IκBα, negative feedback, High confidence)
- POU2F1 (High confidence)
- NFIL3 (High confidence)
Additional regulators with evidence: TNF, TLR4, TLR6 (inflammatory signals); ATF3, STAT3, AP1 (stress/immune response); SMAD2/3 (TGF-β pathway); NR4A1, PPARG (metabolic/anti-inflammatory)
Downstream targets
IL1B acts as a paracrine/autocrine regulator, controlling 20+ downstream targets including:
- Activates: IL6, MMP3, VCAM1, SELE (endothelial adhesion); CLDN1, ITGA2 (cell adhesion); GCH1, HAS2, LGALS9
- Represses: GDF5, KRT1, ITGA3, SCNN1A, DIO1, ENPP1
Evidence type: Primarily inferred from signal transduction (cytokine signaling via IL1 receptors) and computational predictions; direct transcriptional targets require experimental validation via ChIP-seq or reporter assays.
Drug & pharmacology data
IL1B (Interleukin-1 beta) is a well-established drug target. The IL1B protein (CHEMBL1909490 in ChEMBL) has 293 molecules actively documented as targeting it in ChEMBL, with 422 recorded bioactivity assays.
Targeting Molecules: TOP APPROVED & ADVANCED DRUGS
Phase 4 (FDA Approved) — 3 drugs:
| Molecule ID | Name | Type | Mechanism | Approved |
|---|---|---|---|---|
| CHEMBL1201570 | Anakinra (Kineret) | Protein | IL-1 Receptor Antagonist | 2001 |
| CHEMBL1201834 | Canakinumab (Ilaris) | Antibody | Anti-IL-1β Monoclonal Antibody | 2009 |
| CHEMBL1201830 | Rilonacept (Arcalyst) | Protein | IL-1 Trap (IL-1α/β Inhibitor) | 2008 |
Phase 3 (Clinical Trial) — 1 advanced drug:
| Molecule ID | Name | Type | Mechanism |
|---|---|---|---|
| CHEMBL1743026 | Gevokizumab (XOMA 052) | Antibody | Anti-IL-1β Monoclonal Antibody |
Phase 2 (Clinical Trial) — 1 drug in development:
| Molecule ID | Name | Type | Mechanism |
|---|---|---|---|
| CHEMBL3989943 | Dapansutrile (OLT-1177) | Small Molecule | NLRP3 Inflammasome Inhibitor |
Clinical Trials: TOP 20 by Status & Phase
Anakinra (153 total trials) — Top Phase 4 trials:
- NCT06697431 | Non-Inferiority Kawasaki Trial With Anakinra | NOT_YET_RECRUITING | Phase 4
- NCT06624436 | Immunomodulatory Effects (Dexamethasone/Tocilizumab/Anakinra) in Endotoxemia | RECRUITING | Phase 4
- NCT06666335 | Efficacy & Safety in Colchicine-Resistant FMF (Chinese patients) | NOT_YET_RECRUITING | Phase 4
- NCT02735707 | Community-Acquired Pneumonia Platform Trial | RECRUITING | Phase 3
- NCT07281027 | COMBAT-NORSE: Anakinra vs Tocilizumab | NOT_YET_RECRUITING | Phase 3
- NCT05926505 | Safety & Efficacy in Post-Acute COVID Syndrome | RECRUITING | Phase 2/3
- NCT05814159 | Anakinra in Still’s Disease (Japanese patients) | ACTIVE_NOT_RECRUITING | Phase 3
Canakinumab (98 total trials) — Top Phase 3/4 trials:
- NCT05080218 | COVID-19 Vaccine Response in Rheumatology Patients | COMPLETED | Phase 4
- NCT04362813 | Efficacy & Safety in COVID-19 Pneumonia with CRS | COMPLETED | Phase 3
- NCT05401578 | Treatment of Postprandial Hypoglycemia | RECRUITING | Phase 3
- NCT04717635 | Efficacy & Safety in Adult-Onset Still’s Disease (Japanese) | COMPLETED | Phase 3
- NCT03626545 | Canakinumab + Docetaxel in NSCLC (2nd/3rd line) | TERMINATED | Phase 3
- NCT01327846 | Cardiovascular Risk Reduction Study | COMPLETED | Phase 3
Rilonacept (26 total trials) — Top Phase 3/4 trials:
- NCT01663103 | IL-1 Trap in Vascular Dysfunction/Chronic Kidney Disease | COMPLETED | Phase 4
- NCT03737110 | Efficacy & Safety in Recurrent Pericarditis | COMPLETED | Phase 3
- NCT00829829 | PREventative Study Against Urate-Lowering Drug-Induced Gout Exacerbations | COMPLETED | Phase 3
- NCT00855920 | Study Utilizing Rilonacept in Gout Exacerbations (SURGE) | COMPLETED | Phase 3
Gevokizumab (23 total trials):
- Phase 3 and Phase 2 trials across acne, gout, rheumatologic conditions
Pharmacogenomics
IL1B Polymorphisms & Drug Response:
- IL1B is flagged as a VIP (Very Important Pharmacogene) in PharmGKB but currently lacks CPIC clinical dosing guidelines
- No specific pharmacogenomics interactions documented in biobtree for IL1B-targeting drugs that affect dosing
- Clinical efficacy with IL1B inhibitors varies by patient genotype and disease context (particularly in autoinflammatory syndromes and rheumatologic conditions), but standardized dosing guidelines are not established
Known Clinical Associations:
- IL1B genetic variants associated with inflammatory disease susceptibility
- Response to anakinra/canakinumab varies in autoinflammatory syndromes (CAPS, FMF, AOSD) but no genotype-based dosing adjustments currently recommended
Expression profiles
Tissue Expression (Bgee)
IL1B shows ubiquitous expression across 228/282 tissues and organs tested (max score: 99.48/100, average: 63.3). Expression is particularly strong in immune and barrier tissues.
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Periodontal ligament | 99.48 | Gold |
| 2 | Blood | 92.04 | Gold |
| 3 | Bone marrow | 89.22 | Gold |
| 4 | Cartilage tissue | 87.85 | Gold |
| 5 | Gall bladder | 86.14 | Gold |
| 6 | Vermiform appendix | 86.05 | Gold |
| 7 | Decidua | 85.12 | Gold |
| 8 | Spleen | 83.86 | Gold |
| 9 | Mucosa of urinary bladder | 82.46 | Gold |
| 10 | Parietal pleura | 81.02 | Gold |
| 11 | Caecum | 80.81 | Gold |
| 12 | Smooth muscle tissue | 79.99 | Gold |
| 13 | Palpebral conjunctiva | 79.38 | Gold |
| 14 | Body of stomach | 78.47 | Gold |
| 15 | Gingival epithelium | 78.35 | Gold |
Expression breadth: IL1B is highly expressed in immune tissues (blood, bone marrow, spleen), mucosal barriers (GI tract, urinary bladder, gingiva), and connective tissues. Expression is strong across both lymphoid and myeloid compartments.
Cell Type Expression (Bgee)
| Rank | Cell Type | Expression Score | Quality |
|---|---|---|---|
| 1 | Granulocyte | 93.93 | Gold |
| 2 | Monocyte | 93.30 | Gold |
| 3 | Leukocyte (general) | 92.97 | Gold |
| 4 | Mononuclear cell | 92.85 | Gold |
| 5 | Bone marrow cell | 91.60 | Gold |
| 6 | Pancreatic ductal cell | 86.65 | Silver |
| 7 | Stromal cell of endometrium | 81.80 | Gold |
| 8 | Buccal mucosa cell | 81.01 | Gold |
| 9 | Epithelial cell of pancreas | 78.29 | Silver |
Cell-type pattern: IL1B is predominantly expressed in myeloid lineage cells (granulocytes, monocytes) and bone marrow progenitors, consistent with its role as a pro-inflammatory cytokine. Tissue-resident immune populations and mucosal epithelial cells also show substantial expression.
Single-Cell Expression Datasets (SCXA)
14 datasets containing IL1B expression data across diverse human tissues and conditions:
| Dataset | Tissues/Sample | Cell Count | Key Cell Types |
|---|---|---|---|
| E-CURD-46 | Crohn’s disease lesions | 124,518 | Immune infiltrates, disease-associated cells |
| E-HCAD-1 | Ischemic tissue sensitivity | 425,435 | Multi-tissue baseline |
| E-HCAD-36 | Aortic tissue (control vs. aneurysmal) | 71,332 | Vascular cells, immune cells |
| E-GEOD-149689 | COVID-19 vs. influenza PBMCs | 166,852 | T cells, B cells, myeloid cells |
| E-GEOD-130148 | Human lung (fresh tissue) | 14,560 | Alveolar macrophages, dendritic cells |
| E-GEOD-135922 | Retinal pigment epithelium/choroid | 55,571 | RPE, immune infiltrates |
| E-HCAD-6 | Bone marrow CD34+ cells | 34,596 | Hematopoietic progenitors |
| E-MTAB-9067 | Fetal liver & bone marrow | 5,865 | Hematopoietic lineages, granulocytes, monocytes |
| E-MTAB-6075 | THP-1 macrophages (LPS/palmitate) | 254 | Immune-activated cells |
| E-GEOD-89232 | Dendritic cells (blood & cord blood) | 957 | cDC, pre-cDC populations |
| E-GEOD-84465 | Glioblastoma infiltrating cells | 3,588 | Immune infiltrates, glioma cells |
| E-MTAB-8559 | Ovarian cancer models | 20,982 | Tumor microenvironment |
| E-CURD-7, E-ENAD-21 | Adult breast epithelial cells | 867 | Epithelial, immune cells |
Single-cell patterns: IL1B is strongly expressed in innate immune cells (monocytes, macrophages, dendritic cells, granulocytes), particularly in inflammatory contexts (infection, tissue injury, disease). Expression in tumor microenvironments and disease lesions reflects IL1B’s role as a prototypic pro-inflammatory mediator.
Disease associations
Mendelian / Monogenic Diseases
IL1B mutations show limited direct monogenic disease associations, with the following documented cases:
| Disease | Disease ID | Inheritance | Evidence | Notes |
|---|---|---|---|---|
| Cholangiocarcinoma | Orphanet: 70567; MONDO:0019087 | Not specified | ClinVar variants | 4 genes implicated; associated phenotypes: jaundice, pruritus, fever, abdominal pain, anorexia, acholic stools, fatigue, biliary tract neoplasm |
| Antisynthetase Syndrome | Orphanet: 81 | Not specified | ClinVar variants | Rare autoimmune disease; 44 phenotypes documented including muscle weakness, respiratory insufficiency, pulmonary fibrosis, myalgia, myositis |
| Hereditary Diffuse Gastric Adenocarcinoma | MONDO:0007648 | Unknown | GenCC (No Known Disease Relationship) | Classified as “No Known Disease Relationship” by Labcorp Genetics (Invitae); evidence uncertainty |
Phenotype Associations (HPO Terms)
Three HPO terms directly associated with IL1B mutations:
- HP:0001442 — Typified by somatic mosaicism
- HP:0012126 — Stomach cancer
- HP:0410067 — Increased level of L-fucose in urine
Additional phenotypes from rare disease associations (Orphanet):
- Cholangiocarcinoma phenotypes: Jaundice (HP:0000952), Pruritus (HP:0000989), Fever (HP:0001945), Abdominal pain (HP:0002027), Fatigue (HP:0012378)
- Antisynthetase Syndrome phenotypes (44 total): Muscle weakness (HP:0001324), Respiratory insufficiency (HP:0002093), Pulmonary fibrosis (HP:0002206), Autoimmunity (HP:0002960), Myalgia (HP:0003326), Myositis (HP:0100614), Arthritis (HP:0001369), Raynaud phenomenon (HP:0030880)
Complex-Disease / GWAS Associations
Five independent GWAS signals at the IL1B locus (chromosome 2q14.1):
| Trait | SNP | Effect Allele | P-value | Effect Size | RAF | Study | Ref |
|---|---|---|---|---|---|---|---|
| Allergic disease (asthma, hay fever, eczema) | rs1143633 | C | 2.0e-10 | OR 1.034 [1.02-1.04] | 0.70 | Ferreira et al., 2017 | PMID: 29083406 |
| Dysmenorrheic pain severity | rs80111889 | G | 2.0e-16 | 0.425 [0.32-0.53] unit decrease | 0.74 | Hirata et al., 2018 | PMID: 29855537 |
| Birth weight | rs11680809 | A | 3.0e-08 | 0.0145 [0.009-0.020] unit increase | 0.57 | Warrington et al., 2019 | PMID: 31043758 |
| Gestational age at birth (child effect) | rs7594852 | C | 4.0e-14 | 0.034 [0.025-0.043] unit increase | 0.53 | Liu et al., 2019 | PMID: 31477735 |
| Post-term birth | rs7594852 | C | 4.0e-08 | OR 1.1 [1.06-1.14] | 0.53 | Liu et al., 2019 | PMID: 31477735 |
Additional complex disease associations via ClinVar:
- Endometriosis (MONDO:0005133)
- Coronary heart disease, susceptibility to, 2 (MONDO:0012009)