IL1A

Summary

IL1A (interleukin 1 alpha, HGNC:5991) is a protein-coding gene on chromosome 2q14.1, encoding Interleukin-1 alpha (P01583). Cytokine constitutively present intracellularly in nearly all resting non-hematopoietic cells that plays an important role in inflammation and bridges the innate and adaptive immune systems.

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritis and Alzheimer’s disease.

Source: NCBI Gene 3552 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 47 total
• Druggable target: yes
• MANE Select transcript: NM_000575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5991
Approved symbol	IL1A
Name	interleukin 1 alpha
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	IL1F1, IL-1A, IL1-ALPHA
Ensembl gene	ENSG00000115008
Ensembl biotype	protein_coding
OMIM	147760
Entrez	3552

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000263339, ENST00000959423

RefSeq mRNA: 2 — MANE Select: NM_000575 NM_000575, NM_001371554

CCDS: CCDS2101

Canonical transcript exons

ENST00000263339 — 7 exons

Exon	Start	End
ENSE00000773892	112777987	112778111
ENSE00000773893	112779496	112779666
ENSE00000856832	112781604	112781826
ENSE00001128606	112773925	112775267
ENSE00001128612	112783724	112783778
ENSE00001145252	112782716	112782764
ENSE00001325622	112784443	112784493

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 94.01.

FANTOM5 (CAGE): breadth broad, TPM avg 36.7033 / max 6511.5509, expressed in 536 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30177	36.7033	536

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	94.01	gold quality
oral cavity	UBERON:0000167	85.46	gold quality
buccal mucosa cell	CL:0002336	84.78	gold quality
esophagus squamous epithelium	UBERON:0006920	84.05	gold quality
lower esophagus mucosa	UBERON:0035834	83.59	gold quality
mucosa of urinary bladder	UBERON:0001259	80.85	gold quality
epithelium of esophagus	UBERON:0001976	80.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.40	gold quality
gingiva	UBERON:0001828	78.07	gold quality
esophagus mucosa	UBERON:0002469	77.41	gold quality
squamous epithelium	UBERON:0006914	76.85	gold quality
right testis	UBERON:0004534	76.04	gold quality
left testis	UBERON:0004533	75.85	gold quality
gingival epithelium	UBERON:0001949	74.81	gold quality
testis	UBERON:0000473	73.94	gold quality
tongue squamous epithelium	UBERON:0006919	73.61	silver quality
islet of Langerhans	UBERON:0000006	70.26	gold quality
decidua	UBERON:0002450	68.28	gold quality
cartilage tissue	UBERON:0002418	67.88	gold quality
type B pancreatic cell	CL:0000169	66.92	gold quality
amniotic fluid	UBERON:0000173	66.68	gold quality
gall bladder	UBERON:0002110	65.18	gold quality
urinary bladder	UBERON:0001255	64.07	gold quality
body of tongue	UBERON:0011876	62.90	gold quality
upper leg skin	UBERON:0004262	61.39	gold quality
tonsil	UBERON:0002372	61.38	gold quality
vermiform appendix	UBERON:0001154	60.60	gold quality
male germ cell	CL:0000015	59.87	silver quality
esophagus	UBERON:0001043	59.51	gold quality
upper arm skin	UBERON:0004263	59.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-11	yes	100.32
E-ANND-3	yes	7.95

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
FBN1	Repression
LGALS9	Activation
MC1R	Activation
SERPINA3	Activation
TNF	Activation

Upstream regulators (CollecTRI, top): AP1, BCL6, CEBPA, CEBPB, EGR1, EGR4, ESR1, ETV6, FOS, GATA1, IRF6, JUN, JUND, NFE2L2, NFKB1, NFKB2, NFKB, NR3C1, NR4A1, REL, RELA, RELB, SP1, SP3, SP7, TP63, TREM2

miRNA regulators (miRDB)

90 targeting IL1A, 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-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3686	99.90	70.53	2432

Literature-anchored findings (GeneRIF, showing 40)

• The level of IL-1 alpha is significantly higher in sera of cicatricial pemphigoid patients with active disease before intravenous immunoglobulin therapy compared to the post-treatment level. (PMID:11448121)
• Allele specific regulation of cytokine genes: monoallelic expression of the IL-1A gene. Review. (PMID:11774556)
• Interleukin-1 alpha and beta system in testis–quantitative analysis. Expression of immunomodulatory genes in male gonad. (PMID:11774564)
• Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression. (PMID:11940570)
• data indicate that IL-1 gene polymorphisms known to affect the inflammatory response are highly related to plasma levels of CRP and fibrinogen in patients referred for coronary angiography (PMID:11991668)
• Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region (PMID:12037600)
• Results suggest a role for the IL1A gene in modifying the clinical features of migraine. (PMID:12047332)
• Interleukin-1 system plays a role in sex steroid receptor gene expression in human endometrial cancer. (PMID:12051868)
• TNF-alpha promoter polymorphism is associated with Il-1 beta synthesis capacity in human leukocytees (PMID:12101079)
• Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis. (PMID:12115182)
• Review.inheritance of a specific IL-1A gene polymorphism increases risk for development of Alzheimer’s disease by as much as sixfold. Moreover, this increased risk is associated with earlier age of onset of the disease. (PMID:12149413)
• The IL1A genotype associates with atopy in nonasthmatic adults (PMID:12209090)
• Review. The IL-1 family consists of IL-1alpha and IL-1beta, 2 receptors, and a specific receptor antagonist, IL-1Ra. The balance between IL-1 & IL-1Ra in local tissues plays an important role in the susceptibility to & severity of many diseases. (PMID:12220547)
• IL-1A allele 2 is a risk factor for Alzheimer’s disease (AD) in a dose-dependent manner, the risk of developing AD with two copies of the IL-1A allele 2 being approximately double that of one copy of the IL-1A allele 2. (PMID:12242547)
• relationship between interleukin-1A (IL-1A) gene polymorphisms and the susceptibility of chronic periodontitis in Uighur minority in Xingjiang province of China (PMID:12362317)
• IL1-alpha induced during in vitro activation of mast cells by cystic fibrosis-associated Pseudomonas aeruginosa stimulates neutrophil transendothelial migration. (PMID:12370389)
• investigated interleukin polymorphisms in ovarian cancer but did not find any association between common polymorphisms of interleukin 1A, interleukin 1B, and interleukin 1 receptor antagonist and the occurrence of ovarian cancer (PMID:12445604)
• We have identified a novel regulatory sequence at -65 to -41 of the human IL-1alpha promoter (PMID:12453471)
• a “defective” IL-1ra response to IL-1 may underlie, at least in part, the exaggerated prostaglandin-endoperoxide H synthase (PGHS)-2 induction in orbital fibroblasts (PMID:12519748)
• the CTG haplotype of the IL1A gene may be an important marker for the susceptibility to, and the severity of, systemic sclerosis (PMID:12528118)
• that a DNA binding protein containing the Ets domain is constitutively expressed in fibroblasts from the skin of systemic sclerosis patients and regulates transcription of the IL1A gene, contributing to the fibrogenic phenotype of fibroblasts (PMID:12528119)
• soluble form of the IL-1 receptor accessory protein (AcP) increases the affinity of binding of human IL-1alpha and IL-1beta to the soluble human type II IL-1 receptor (PMID:12530978)
• In conjunctiva of keratoconjunctivitis sicca patients. (PMID:12613995)
• The association of the TN7(delTTCA)A haplotype with higher levels of IL-1 alpha expression and reduced risk for ESRD is consistent with involvement of cytokines in risk for developing nephropathy. (PMID:12631337)
• may enhance the local production of CCL3, which may interact with CCR1 expressed on hepatoma cells, in an autocrine and/or paracrine manner (PMID:12651617)
• Low levels of IL-1 alpha mrna expression are associated with an increased risk for cancer specific death in patients with bladder cancer. (PMID:12667716)
• TNF-alpha & IL-1 produced by sickle leukocytes are the primary factors responsible for the observed CAM expression. This & the subsequent endothelial adherence of sickle erythrocytes play roles in the pathophysiology of sickle-related complications. (PMID:12673844)
• IL-1A was used to stimulate epidermal keratinocytes in organ culture. (PMID:12710950)
• no one particular polymorphism in the IL-1 gene cluster yields an advantage for survival in the last decades of life (PMID:12714264)
• Activation of vascular endothelial cells by IL-1alpha released by a pulmonary epithelial cell line infected with respiratory syncytial virus. (PMID:12742380)
• the constitutively up-regulated expression of pre-IL-1 alpha in the nuclei of systemic sclerosis (SSc) fibroblasts up-regulates proliferation and matrix production of SSc fibroblasts through binding necdin (PMID:12913118)
• Monoallelic expression of IL-1 alpha is observed in Th0, Th1, and Th2 cell clones from healthy individuals, as well as in synovial fluid of the knee joint derived from rheumatoid arthritis patients. (PMID:12928381)
• confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction (PMID:12930304)
• In pancreatic cancer, IL-1alpha enhanced alpha(6)beta(1)-integrin expression, probably via increased IL-1RI levels. (PMID:12931024)
• Proapoptotic stimuli upregulate MCP-1 expression by vascular smooth muscle cells through release of interleukin-1alpha. (PMID:12946945)
• IL-1alpha activity in chondrocytes is independent of any direct modification in UDPGD activity and manifests equally in human cartilage of all ages (PMID:13679381)
• Cancer cell-derived cytokines, such as IL-1 alpha, induce cachexia by affecting leptin-dependent metabolic pathways. (PMID:14633625)
• serum IL-1 alpha and IL-1 soluble receptor type 2 levels in women with ovarian cancers were significantly higher than those in cervical cancer, and in patients with benign disorders, and in healthy control (PMID:14674121)
• In IL-1 alpha transgenic mice, which may overproduce membrane-associated (MA)IL-1 as well as soluble IL-1 alpha, severity of arthritis highly correlates with MA-IL-1 activity rather than with soluble IL-1 alpha activity or serum IL-1 alpha concentration. (PMID:14688369)
• The IL-1alpha-889 polymorphism, previously shown to predispose to increased IL-1 protein expression, may be involved in susceptibility to systemic sclerosis (PMID:14705223)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il1a	ENSMUSG00000027399
rattus_norvegicus	Il1a	ENSRNOG00000004575

Protein

Protein identifiers

Interleukin-1 alpha — P01583 (reviewed: P01583)

Alternative names: Hematopoietin-1

All UniProt accessions (1): P01583

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine constitutively present intracellularly in nearly all resting non-hematopoietic cells that plays an important role in inflammation and bridges the innate and adaptive immune systems. After binding to its receptor IL1R1 together with its accessory protein IL1RAP, forms the high affinity interleukin-1 receptor complex. Signaling involves the recruitment of adapter molecules such as MYD88, IRAK1 or IRAK4. In turn, mediates the activation of NF-kappa-B and the three MAPK pathways p38, p42/p44 and JNK pathways. Within the cell, acts as an alarmin and cell death results in its liberation in the extracellular space after disruption of the cell membrane to induce inflammation and alert the host to injury or damage. In addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, directly senses DNA damage and acts as a signal for genotoxic stress without loss of cell integrity.

Subunit / interactions. Monomer. Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion. Interacts with IL1R1. Interacts with S100A13; this interaction is the first step in the export of IL1A, followed by direct translocation of this complex across the plasma membrane.

Subcellular location. Nucleus. Cytoplasm. Secreted.

Post-translational modifications. Acetylated within its nuclear localization sequence, which impacts subcellular localization. Proteolytic processed by CAPN1 in a calcium-dependent manner. Cleavage from 31 kDa precursor to 18 kDa biologically active molecules. Phosphorylated. Phosphorylation greatly enhances susceptibility to digestion and promotes the conversion of pre-IL1A alpha to the biologically active IL1A.

Domain organisation. The similarity among the IL-1 precursors suggests that the amino ends of these proteins serve some as yet undefined function.

Similarity. Belongs to the IL-1 family.

RefSeq proteins (2): NP_000566, NP_001358483 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000975	IL-1_fam	Family
IPR003295	IL-1_alpha	Family
IPR003502	IL-1_propep	Domain
IPR008996	IL1/FGF	Homologous_superfamily
IPR020877	IL-1_CS	Conserved_site

Pfam: PF00340, PF02394

UniProt features (35 total): strand 18, sequence variant 5, helix 2, modified residue 2, lipid moiety-binding region 2, glycosylation site 2, propeptide 1, chain 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5UC6	X-RAY DIFFRACTION	2.1
2ILA	X-RAY DIFFRACTION	2.3
2KKI	SOLUTION NMR
2L5X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01583-F1	74.49	0.52

Functional residue map

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

Post-translational modifications (4): 82, 87, 82, 83

Glycosylation sites (2): 102, 141

Mutagenesis-validated functional residues (1):

Position	Phenotype
82	about 50% loss of cytokine secretion after dna damage.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-448706	Interleukin-1 processing
R-HSA-5620971	Pyroptosis
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9020702	Interleukin-1 signaling
R-HSA-9660826	Purinergic signaling in leishmaniasis infection

MSigDB gene sets: 566 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN

GO Biological Process (29): fever generation (GO:0001660), positive regulation of cytokine production (GO:0001819), connective tissue replacement involved in inflammatory response wound healing (GO:0002248), intracellular sodium ion homeostasis (GO:0006883), apoptotic process (GO:0006915), inflammatory response (GO:0006954), immune response (GO:0006955), negative regulation of cell population proliferation (GO:0008285), positive regulation of vascular endothelial growth factor production (GO:0010575), positive regulation of gene expression (GO:0010628), cytokine-mediated signaling pathway (GO:0019221), positive regulation of interleukin-2 production (GO:0032743), positive regulation of interleukin-6 production (GO:0032755), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of immature T cell proliferation in thymus (GO:0033092), cellular response to heat (GO:0034605), ectopic germ cell programmed cell death (GO:0035234), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of angiogenesis (GO:0045766), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of transcription by RNA polymerase II (GO:0045944), response to copper ion (GO:0046688), positive regulation of protein secretion (GO:0050714), positive regulation of cell division (GO:0051781), regulation of ERK1 and ERK2 cascade (GO:0070372), cellular response to lipopolysaccharide (GO:0071222), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), response to stress (GO:0006950)

GO Molecular Function (4): cytokine activity (GO:0005125), interleukin-1 receptor binding (GO:0005149), copper ion binding (GO:0005507), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Interleukin-1 family signaling	2
Signaling by Interleukins	2
Cellular Senescence	1
Regulated Necrosis	1
Cell recruitment (pro-inflammatory response)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	3
cellular anatomical structure	3
acute-phase response	1
heat generation	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
wound healing involved in inflammatory response	1
connective tissue replacement	1
intracellular monoatomic cation homeostasis	1
sodium ion homeostasis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
immune system process	1
response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
interleukin-2 production	1
regulation of interleukin-2 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
immature T cell proliferation in thymus	1
regulation of immature T cell proliferation in thymus	1
positive regulation of immature T cell proliferation	1
response to heat	1
cellular response to stress	1

Protein interactions and networks

STRING

5063 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL1A	IL1R1	P14778	999
IL1A	IL2	P01585	997
IL1A	IL1RAP	Q9NPH3	997
IL1A	IL1R2	P27930	996
IL1A	MYD88	P78397	996
IL1A	IL18	Q14116	995
IL1A	IL3	P08700	994
IL1A	IL4	P05112	993
IL1A	CSF2	P04141	992
IL1A	IL1RN	P18510	988
IL1A	CSF3	P09919	983
IL1A	IL1B	P01584	983
IL1A	TNF	P01375	976
IL1A	IL6	P05231	975
IL1A	TLR4	O00206	973
IL1A	CCL11	P50877	973

IntAct

24 interactions, top by confidence:

A	B	Type	Score
IL1A	IL1R2	psi-mi:“MI:0915”(physical association)	0.660
IL1A	IL1R2	psi-mi:“MI:2364”(proximity)	0.660
HAX1	IL1A	psi-mi:“MI:0915”(physical association)	0.620
IL1A	HAX1	psi-mi:“MI:0915”(physical association)	0.620
IL1A	HAX1	psi-mi:“MI:0914”(association)	0.620
IL1A	KPNA6	psi-mi:“MI:0915”(physical association)	0.560
IL1A	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
IL1A	CASP1	psi-mi:“MI:0915”(physical association)	0.520
IL1A	CASP1	psi-mi:“MI:0915”(physical association)	0.400
CASP1	IL1A	psi-mi:“MI:0915”(physical association)	0.400
IL1A	CLIC3	psi-mi:“MI:0915”(physical association)	0.400
IL1A	SHARPIN	psi-mi:“MI:0915”(physical association)	0.400
IL1A	BPTF	psi-mi:“MI:0914”(association)	0.350
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (84): IL1A (Synthetic Growth Defect), IL1R2 (Co-localization), KPNA6 (Two-hybrid), MEOX2 (Two-hybrid), NDN (Affinity Capture-Western), S100A13 (Affinity Capture-Western), HAX1 (Two-hybrid), HAX1 (Reconstituted Complex), IL1A (Reconstituted Complex), HAX1 (Far Western), HAX1 (Affinity Capture-Western), IL1A (Affinity Capture-RNA), IL1A (Affinity Capture-RNA), IL1A (Affinity Capture-RNA), IL1A (Affinity Capture-RNA)

ESM2 similar proteins: A4UYK8, O46612, O46613, P01582, P01583, P01584, P04822, P08831, P09428, P10749, P14628, P16598, P18430, P21621, P26889, P41687, P46648, P48089, P48090, P51493, P51745, P79161, P79162, P79182, P79340, Q14D04, Q28292, Q28385, Q28386, Q28579, Q2HZH0, Q2MH07, Q32NG6, Q3HWU1, Q3UIR3, Q63264, Q6PUD2, Q6R2X3, Q6ZUJ8, Q865X7

Diamond homologs: O46612, O46613, P01582, P01583, P04822, P08831, P16598, P18430, P46647, P48089, P79161, P79340, Q28385, Q28579, Q3HWU1, Q60480, Q865X7

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
IL1A	up-regulates	Inflammation
IL1A	“down-regulates quantity by repression”	FBN1	“transcriptional regulation”
IL1A	“up-regulates quantity by expression”	TNF	“transcriptional regulation”
“UVB radiation”	up-regulates	IL1A
IL1A	“up-regulates quantity by expression”	MC1R	“transcriptional regulation”
IL1A	“up-regulates quantity by expression”	SERPINA3	“transcriptional regulation”
IL1A	“up-regulates activity”	IL1R1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

780 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112775193:AGTG:A	donor_gain	1.0000
2:112777982:CTGA:C	donor_loss	1.0000
2:112777983:TGA:T	donor_loss	1.0000
2:112777984:GACCT:G	donor_loss	1.0000
2:112777986:C:CA	donor_loss	1.0000
2:112778112:C:CC	acceptor_gain	1.0000
2:112778129:C:CT	acceptor_gain	1.0000
2:112781598:CCTTA:C	donor_loss	1.0000
2:112781599:CTTA:C	donor_loss	1.0000
2:112781600:TTAC:T	donor_loss	1.0000
2:112781601:TACCT:T	donor_loss	1.0000
2:112781602:A:AC	donor_gain	1.0000
2:112781602:ACCTT:A	donor_gain	1.0000
2:112781603:C:CC	donor_gain	1.0000
2:112781603:C:CG	donor_loss	1.0000
2:112781603:CCTT:C	donor_gain	1.0000
2:112781603:CCTTC:C	donor_gain	1.0000
2:112781606:T:TA	donor_gain	1.0000
2:112781822:GATTT:G	acceptor_gain	1.0000
2:112781824:TTT:T	acceptor_gain	1.0000
2:112781825:TT:T	acceptor_gain	1.0000
2:112781825:TTCT:T	acceptor_loss	1.0000
2:112781827:C:A	acceptor_loss	1.0000
2:112781827:C:CC	acceptor_gain	1.0000
2:112781829:G:C	acceptor_gain	1.0000
2:112782711:CTTA:C	donor_loss	1.0000
2:112782712:TTA:T	donor_loss	1.0000
2:112782713:TA:T	donor_loss	1.0000
2:112782714:A:C	donor_loss	1.0000
2:112782760:TTTCA:T	acceptor_gain	1.0000

AlphaMissense

1813 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112775182:A:G	F234S	0.995
2:112778105:A:G	F166S	0.991
2:112778104:A:C	F166L	0.989
2:112778104:A:T	F166L	0.989
2:112778106:A:G	F166L	0.989
2:112775181:G:C	F234L	0.985
2:112775181:G:T	F234L	0.985
2:112775183:A:G	F234L	0.985
2:112775092:A:G	F264S	0.983
2:112775214:G:C	F223L	0.983
2:112775214:G:T	F223L	0.983
2:112775216:A:G	F223L	0.983
2:112778051:A:T	L184Q	0.983
2:112775182:A:C	F234C	0.982
2:112775215:A:G	F223S	0.982
2:112778051:A:G	L184P	0.978
2:112778024:A:T	V193E	0.977
2:112778091:A:C	Y171D	0.977
2:112778051:A:C	L184R	0.976
2:112778057:A:T	V182E	0.976
2:112779531:A:T	L152H	0.976
2:112775149:G:T	A245D	0.974
2:112778105:A:C	F166C	0.973
2:112778028:A:C	Y192D	0.972
2:112779555:A:T	I144K	0.970
2:112775150:C:G	A245P	0.969
2:112779574:C:G	D138H	0.964
2:112779584:G:C	F134L	0.963
2:112779584:G:T	F134L	0.963
2:112779586:A:G	F134L	0.963

dbSNP variants (sampled 300 via entrez): RS1000011727 (2:112779933 A>G), RS1000330985 (2:112780043 A>G), RS1000914205 (2:112785256 T>C), RS1001569377 (2:112783091 C>T), RS1001825596 (2:112781671 T>C), RS1002024920 (2:112782655 T>G), RS1002089664 (2:112781415 G>A,C), RS1002178572 (2:112775861 T>A,C), RS1002204797 (2:112775558 G>A), RS1002404117 (2:112776214 G>A,C), RS1002564168 (2:112783056 T>G), RS1003727473 (2:112784359 A>G), RS1004191767 (2:112779395 T>C), RS1004442736 (2:112777112 T>C,G), RS1004468648 (2:112786096 A>G)

Disease associations

OMIM: gene MIM:147760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000797_2	Endometriosis	3.000000e-06
GCST000883_10	Response to antipsychotic treatment in schizophrenia (working memory)	7.000000e-07
GCST004549_14	Endometriosis	1.000000e-09
GCST004549_29	Endometriosis	5.000000e-08
GCST006104_6	Interleukin-1-receptor antagonist levels	1.000000e-06
GCST006656_2	Dysmenorrheic pain severity	2.000000e-16
GCST008751_1	Gestational age at birth (child effect)	4.000000e-14
GCST008752_1	Post-term birth	4.000000e-08
GCST90002398_346	Neutrophil count	2.000000e-15
GCST90002399_156	Neutrophil percentage of white cells	4.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004335	short-term memory
EFO:0004754	interleukin 1 receptor antagonist measurement
EFO:0007889	dysmenorrheic pain measurement
EFO:0005112	gestational age
EFO:0006921	birth measurement
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580496 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11677416	Efficacy	3	olanzapine	Schizophrenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11677416	IL1A	3	0.00	1	olanzapine
rs1800587	IL1A		0.00	0
rs17561	IL1A		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases reaction, decreases reaction, increases expression, affects cotreatment, decreases expression (+1 more)	19
Particulate Matter	affects cotreatment, increases reaction, increases secretion, decreases expression, decreases reaction (+2 more)	16
Benzo(a)pyrene	decreases reaction, increases expression	8
Tobacco Smoke Pollution	decreases expression, increases expression	8
sodium arsenite	decreases reaction, increases expression, decreases expression	7
Sodium Dodecyl Sulfate	affects reaction, increases secretion, decreases expression, increases expression	7
Silicon Dioxide	increases reaction, increases secretion, affects reaction, decreases reaction, increases expression	6
(+)-JQ1 compound	decreases expression, increases expression	5
Resveratrol	affects cotreatment, increases activity, increases expression, decreases reaction, increases reaction (+1 more)	5
Air Pollutants	decreases reaction, increases abundance, increases expression, increases reaction, affects cotreatment (+2 more)	5
Vehicle Emissions	affects cotreatment, decreases reaction, affects expression, affects reaction, increases reaction (+2 more)	5
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	5
cinnamaldehyde	affects expression, affects response to substance, increases expression, affects cotreatment, affects reaction	4
Acetylcysteine	increases reaction, affects cotreatment, increases expression, decreases reaction	4
Benzalkonium Compounds	increases expression, increases secretion	4
Bleomycin	increases expression, increases reaction, decreases reaction	4
Hydrogen Peroxide	decreases reaction, increases expression, decreases expression	4
Methotrexate	increases expression, decreases expression, affects cotreatment	4
Paraquat	increases expression, increases reaction	4
Nanotubes, Carbon	increases expression, decreases expression	4
nickel chloride	increases secretion, increases expression, affects cotreatment	3
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	3
SB 203580	affects cotreatment, decreases reaction, increases secretion, increases expression	3
monomethylarsonous acid	decreases expression, increases expression	3
Arsenic Trioxide	decreases expression, increases expression	3
Ethanol	affects cotreatment, decreases expression, decreases reaction, increases expression, increases secretion (+1 more)	3
Arsenic	decreases expression, increases expression, affects cotreatment	3
Dinitrochlorobenzene	affects secretion, decreases reaction, increases expression	3
Estradiol	affects binding, decreases reaction, increases reaction, increases secretion, decreases expression (+2 more)	3
Plant Extracts	increases expression, affects reaction, decreases expression, decreases reaction, increases abundance	3

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5510950	Binding	Antagonist activity at human recombinant His-tagged wild type IL-1 alpha assessed as inhibition of IL-1 alpha/Alexa 647 labeled human IL-1R1 (1 to 332) interaction preincubated with IL-1 alpha for 1 hr followed by IL-1R1 addition and measur	Ligandability Assessment of IL-1β by Integrated Hit Identification Approaches. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8IA	Abcam HCT 116 IL1A KO	Cancer cell line	Male
CVCL_B8XA	Abcam MCF-7 IL1A KO	Cancer cell line	Female
CVCL_B9KJ	Abcam A-549 IL1A KO	Cancer cell line	Male
CVCL_E0EY	Ubigene HeLa IL1A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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