S100A12

Summary

S100A12 (S100 calcium binding protein A12, HGNC:10489) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A12 (P80511). S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response.

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein is proposed to be involved in specific calcium-dependent signal transduction pathways and its regulatory effect on cytoskeletal components may modulate various neutrophil activities. The protein includes an antimicrobial peptide which has antibacterial activity.

Source: NCBI Gene 6283 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_005621

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10489
Approved symbol	S100A12
Name	S100 calcium binding protein A12
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	p6, MRP6, CGRP, CAAF1, CAGC, ENRAGE
Ensembl gene	ENSG00000163221
Ensembl biotype	protein_coding
OMIM	603112
Entrez	6283

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368737

RefSeq mRNA: 1 — MANE Select: NM_005621 NM_005621

CCDS: CCDS1037

Canonical transcript exons

ENST00000368737 — 3 exons

Exon	Start	End
ENSE00001072568	153374455	153374612
ENSE00001447874	153373711	153373967
ENSE00001935189	153375552	153375621

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 99.90.

FANTOM5 (CAGE): breadth broad, TPM avg 81.8598 / max 53130.2680, expressed in 344 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14610	81.7027	344
14608	0.1004	43
14609	0.0566	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.90	gold quality
monocyte	CL:0000576	99.80	gold quality
bone marrow	UBERON:0002371	99.80	gold quality
mononuclear cell	CL:0000842	99.75	gold quality
leukocyte	CL:0000738	99.74	gold quality
granulocyte	CL:0000094	99.58	gold quality
bone marrow cell	CL:0002092	99.57	gold quality
blood	UBERON:0000178	98.96	gold quality
right lung	UBERON:0002167	98.14	gold quality
periodontal ligament	UBERON:0008266	97.62	gold quality
spleen	UBERON:0002106	97.16	gold quality
upper lobe of left lung	UBERON:0008952	94.98	gold quality
upper lobe of lung	UBERON:0008948	93.37	gold quality
lower esophagus mucosa	UBERON:0035834	93.24	gold quality
esophagus mucosa	UBERON:0002469	92.67	gold quality
gingiva	UBERON:0001828	90.82	gold quality
gingival epithelium	UBERON:0001949	90.32	gold quality
cervix epithelium	UBERON:0004801	89.10	gold quality
amniotic fluid	UBERON:0000173	88.50	gold quality
epithelium of esophagus	UBERON:0001976	87.93	gold quality
oral cavity	UBERON:0000167	87.82	gold quality
esophagus squamous epithelium	UBERON:0006920	86.80	gold quality
squamous epithelium	UBERON:0006914	86.76	gold quality
vagina	UBERON:0000996	84.52	gold quality
pharyngeal mucosa	UBERON:0000355	84.38	gold quality
tongue squamous epithelium	UBERON:0006919	83.67	silver quality
lower lobe of lung	UBERON:0008949	83.16	gold quality
omental fat pad	UBERON:0010414	82.54	gold quality
peritoneum	UBERON:0002358	82.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.79	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	39431.68
E-HCAD-10	yes	15481.64
E-HCAD-1	yes	12582.80
E-MTAB-7407	yes	7789.97
E-HCAD-4	yes	6485.08
E-MTAB-9067	yes	5256.24
E-HCAD-32	yes	5229.00
E-CURD-55	yes	5141.65
E-GEOD-149689	yes	3320.00
E-GEOD-139324	yes	3158.40
E-MTAB-8207	yes	3043.93
E-MTAB-8322	yes	2361.63
E-CURD-120	yes	2194.22
E-CURD-122	yes	89.42
E-MTAB-9467	yes	46.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG, SP1, SP3, TP53

miRNA regulators (miRDB)

12 targeting S100A12, 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-574-5P	100.00	66.01	989
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-6858-5P	96.05	64.59	1020

Literature-anchored findings (GeneRIF, showing 40)

• The antimicrobial peptide calcitermin was isolated from human airway secretions and targets Gram-negative bacteria. (PMID:11522286)
• Circulating CGRP in fulminant hepatic failure seems to reflect hemodynamic changes in the systemic rather than in the cerebral circulation. (PMID:11884208)
• Deficiency of CGRP in Familial Dysautonomia patients may explain some of their symptoms. (PMID:11884210)
• Proinflammatory myeloid-related protein S100A12 induces a dose- and time-dependent activation of the HIV-1 long terminal repeat promoter region that can be blocked by specific polyclonal antibody and by physical denaturation of the protein. (PMID:12218151)
• S100A12 induces inflammatory activation of endothelial cells [review]. (PMID:12697438)
• S100A12 is highly expressed and shows a close correlation with disease activity in a systemic human vasculitis (Kawasaki disease). (PMID:12699958)
• S100A12 is highly expressed in inflammatory bowel disease and down-regulated by anti-TNF therapy. Secretion of S100A12 is induced by TNF. (PMID:12740341)
• Serum concentrations of S100A12 are useful markers for monitoring disease activity in juvenile rheumatoid arthritis. (PMID:15077313)
• This study indicates a potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in Alzheimer’s disease (PMID:16253391)
• Fecal S100A12 is expressed in feces of children with Crohn’s disease (PMID:16804393)
• the function of S100A12 is suppressed by olopatadine in THP-1 monocytes (PMID:16864903)
• Ca2+ binding creates two symmetric hydrophobic surfaces on Ca2+-calgranulin C that allow calgranulin C to bind to the C-type immunoglobulin domain of the receptor for advanced glycation products (RAGE). (PMID:17158877)
• The pattern of S100A4 expression differed significantly from that of the proinflammatory proteins S100A9 and S100A12, which were restricted to phagocytes and granulocytes. (PMID:17328050)
• Data suggest that S100 proteins calprotectin and S100A12 are related to radiographic changes rather than disease activity in psoriatic arthritis with low disease activity. (PMID:17787039)
• Serum calprotectin and S100A12 are increased in children with inflammatory bowel disease and indicate disease activity. (PMID:17852869)
• Calculating the S100A12:sRAGE ratio might help to detect patients with KD who are at risk of being unresponsive to IVIG therapy. (PMID:18050248)
• These results suggest that S100A12 may be a sensitive marker of subclinical inflammation and that an increased S100A12 level may be related to the high peritoneal solute transport rate (PMID:18257809)
• Mast cell and monocyte recruitment by S100A12 (PMID:18292089)
• thermodynamic study of the recombinant S100A12 using circular dichroism, fluorescence and isothermal titration calorimetry (PMID:18346834)
• Human S100A12 is markedly overexpressed in inflammatory compartments, and elevated serum levels of S100A12 are found in patients suffering from various inflammatory, neurodegenerative, metabolic, and neoplastic disorders. (PMID:18443896)
• S100A12 protein is involved in the acceleration of atherosclerosis in hemodialysis patients (PMID:18663285)
• treatment of THP-1 cells with 100 microg of CRP/ml/10(6) cells for 24 h, augmented the expression of RAGE and EN-RAGE genes (PMID:19201044)
• Serum S100A9, S100A8 and S100A12 and RAGE levels were associated not just with RA inflammation and autoantibody production but also with classical vascular risk factors for end-organ damage. (PMID:19284577)
• Oligomerization and target recognition by S100A12 is regulated by zinc and calcium. A potential role of calcium-binding S100 proteins in zinc metabolism and, in particular, the role of S100A12 in the cross talk between zinc and calcium in cell signaling. (PMID:19386136)
• The zinc complex structure shows significant differences from those of both calcium-loaded and apo-S100A12 structures, and comparisons suggest an explanation for the zinc-induced 1500-fold increase in calcium affinity. (PMID:19501594)
• increased expression in sera, synovial tissues and in PBMC of rheumatoid arthritis patients (PMID:19530996)
• S100A12 may represent a new marker of atheroma and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive matrix metalloproteinase (MMP)-2 and MMP-9 colocalized in dimeric zinc-dependent S100A12 complexes. (PMID:19542470)
• Report increased expression of RAGE and EN-RAGE in non-diabetic pre-mature coronary artery disease. (PMID:19576587)
• S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo. (PMID:19875725)
• study demonstrates that besides RAGE also scavenger receptors contribute to distribution, tissue association and elimination of circulating proinflammatory S100A12 (PMID:20025991)
• Data suggest that increased S100A12 levels may point to synovial inflammation of the temporomandibular joint in juvenile idiopathic arthritis. (PMID:20437698)
• Data suggest that the S100A12 expression on circulating endothelial cells may be involved in the development of coronary artery lesions in children with Kawasaki disease. (PMID:20461025)
• carboxylated N-glycans on RAGE enhance binding potential and promote receptor clustering and subsequent signaling events following oligomeric S100A12 binding. (PMID:20512925)
• expression increased in endometriotic cells (PMID:20537326)
• Circulating S100A12 and soluble RAGE are both elevated in hemodialysis patients. However, only S100A12 associates with mortality, partly explained by its links with inflammation. (PMID:20847094)
• Vascular smooth muscle S100A12 accelerates atherosclerosis and augments atherosclerosis-triggered osteogenesis, reminiscent of features associated with plaque instability. (PMID:20966394)
• plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients. (PMID:21258041)
• Transgenic expression of S100A12 in the lung of mice does not exacerbate lung inflammation in a model of OVA-induced allergic inflammation. (PMID:21418345)
• Levels of serum RAGE are reduced in patients with juvenile rheumatoid arthritis and correlate negatively with disease activity and S100A12 levels. (PMID:21724696)
• Although S100A12 levels are not elevated in patients with decreased kidney function, a relation to markers of inflammatory disease is found. (PMID:21822023)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100a10b	ENSDARG00000025254

Paralogs (21): CRNN (ENSG00000143536), S100A8 (ENSG00000143546), S100A7 (ENSG00000143556), S100B (ENSG00000160307), S100A1 (ENSG00000160678), S100A11 (ENSG00000163191), S100A9 (ENSG00000163220), S100P (ENSG00000163993), S100G (ENSG00000169906), S100Z (ENSG00000171643), S100A7A (ENSG00000184330), S100A3 (ENSG00000188015), S100A16 (ENSG00000188643), SNTN (ENSG00000188817), S100A13 (ENSG00000189171), S100A14 (ENSG00000189334), S100A4 (ENSG00000196154), S100A5 (ENSG00000196420), S100A2 (ENSG00000196754), S100A10 (ENSG00000197747), S100A6 (ENSG00000197956)

Protein

Protein identifiers

Protein S100-A12 — P80511 (reviewed: P80511)

Alternative names: CGRP, Calcium-binding protein in amniotic fluid 1, Calgranulin-C, Extracellular newly identified RAGE-binding protein, Migration inhibitory factor-related protein 6, Neutrophil S100 protein, S100 calcium-binding protein A12

All UniProt accessions (1): P80511

UniProt curated annotations — full annotation on UniProt →

Function. S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its pro-inflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of pro-inflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus.

Subunit / interactions. Homodimer. Homooligomer (tetramer or hexamer) in the presence of calcium, zinc and copper ions. Interacts with AGER and both calcium and zinc are essential for the interaction. Interacts with CACYBP in a calcium-dependent manner.

Subcellular location. Secreted. Cytoplasm. Cytoskeleton. Cell membrane.

Tissue specificity. Predominantly expressed by neutrophils, monocytes and activated macrophages. Expressed by eosinophils and macrophages in asthmatic airways in regions where mast cells accumulate. Found in high concentrations in the serum of patients suffering from various inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and Kawasaki disease.

Domain organisation. The hinge domain contributes significantly to its chemotactic properties.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_005612* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain

Pfam: PF01023

UniProt features (36 total): binding site 18, helix 5, strand 4, sequence conflict 3, domain 2, initiator methionine 1, chain 1, peptide 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2WCB	X-RAY DIFFRACTION	1.73
2WCE	X-RAY DIFFRACTION	1.77
2WC8	X-RAY DIFFRACTION	1.88
1E8A	X-RAY DIFFRACTION	1.95
1ODB	X-RAY DIFFRACTION	2.19
1GQM	X-RAY DIFFRACTION	2.7
2WCF	X-RAY DIFFRACTION	2.78
2M9G	SOLUTION NMR
9U7M	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80511-F1	90.46	0.68

Functional residue map

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

Ligand- & substrate-binding residues (18): 24; 26; 26; 27; 32; 62; 64; 66; 68; 73; 86; 86 …

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-6798695	Neutrophil degranulation
R-HSA-879415	Advanced glycosylation endproduct receptor signaling
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-446652	Interleukin-1 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9020702	Interleukin-1 signaling
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome
R-HSA-975871	MyD88 cascade initiated on plasma membrane

MSigDB gene sets: 204 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (16): monocyte chemotaxis (GO:0002548), xenobiotic metabolic process (GO:0006805), inflammatory response (GO:0006954), neutrophil chemotaxis (GO:0030593), killing of cells of another organism (GO:0031640), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAP kinase activity (GO:0043406), endothelial cell migration (GO:0043542), innate immune response (GO:0045087), mast cell activation (GO:0045576), positive regulation of inflammatory response (GO:0050729), defense response to fungus (GO:0050832), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), immune system process (GO:0002376)

GO Molecular Function (8): copper ion binding (GO:0005507), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), calcium-dependent protein binding (GO:0048306), RAGE receptor binding (GO:0050786), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), secretory granule lumen (GO:0034774), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Toll-like Receptor Cascades	7
Innate Immune System	4
Immune System	2
Toll Like Receptor 4 (TLR4) Cascade	2
Toll Like Receptor 2 (TLR2) Cascade	2
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Toll Like Receptor 3 (TLR3) Cascade	1
Interleukin-1 signaling	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
MyD88 cascade initiated on plasma membrane	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
defense response	3
transition metal ion binding	2
protein binding	2
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
metabolic process	1
cellular response to xenobiotic stimulus	1
granulocyte chemotaxis	1
neutrophil migration	1
cell killing	1
disruption of cell in another organism	1
response to bacterium	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
cell migration	1
immune response	1
defense response to symbiont	1
myeloid leukocyte activation	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
response to fungus	1
antimicrobial humoral response	1
biological_process	1
metal ion binding	1
calcium ion binding	1
signaling receptor binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

3166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100A12	AGER	Q15109	997
S100A12	TLR4	O00206	962
S100A12	S100A7	P31151	931
S100A12	HMGB1	P09429	824
S100A12	MPO	P05164	716
S100A12	CXCL8	P10145	698
S100A12	EGFR	P00533	690
S100A12	IL1B	P01584	688
S100A12	TIMP4	Q99727	643
S100A12	MMP9	P14780	631
S100A12	PRL	P01236	629
S100A12	CACYBP	Q9HB71	623
S100A12	CXCL10	P02778	602
S100A12	S100A8	P05109	592
S100A12	SCARB2	Q14108	587

IntAct

30 interactions, top by confidence:

A	B	Type	Score
	S100A12	psi-mi:“MI:0407”(direct interaction)	0.650
	S100A12	psi-mi:“MI:0407”(direct interaction)	0.620
TNF	S100A12	psi-mi:“MI:0407”(direct interaction)	0.620
S100A12	TNF	psi-mi:“MI:0407”(direct interaction)	0.620
S100A12	S100A12	psi-mi:“MI:0407”(direct interaction)	0.560
S100A12	TP53	psi-mi:“MI:0407”(direct interaction)	0.440
S100A12	SLC8A1	psi-mi:“MI:0407”(direct interaction)	0.440
S100A12	AGER	psi-mi:“MI:0407”(direct interaction)	0.440
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
S100A12	thrC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): S100A12 (Affinity Capture-RNA), S100A12 (Co-crystal Structure), S100A12 (Reconstituted Complex)

ESM2 similar proteins: A5PJN0, A7K6Y8, A7K6Y9, F1SSF9, O73763, O76038, O77791, P05109, P06702, P27005, P28318, P28782, P31725, P33763, P43367, P45961, P50115, P50116, P50117, P63083, P63084, P79105, P80511, Q01449, Q06A97, Q0VFG3, Q14ST5, Q28050, Q3MHP3, Q4R6C5, Q5E9G1, Q5SY68, Q5XJX1, Q63ZJ3, Q6AXZ3, Q6DJ05, Q6R556, Q6S5I3, Q75KU4, Q803V3

Diamond homologs: A7K6Y8, A7K6Y9, O77791, P02632, P02633, P02634, P22793, P24480, P29377, P31151, P31725, P50116, P50117, P79105, P80511, P97816, Q14ST5, Q28050, Q503K9, Q6S5I3, Q865V3, Q86SG5, Q8WXG8, O77691, P05964, P06703, P14069, P28318, P30801, P62818, P62819, Q2EN75, P02638, P02639, P04271, P04631, P05942, P06702, P07091, P10462

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

145 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153373964:TATT:T	acceptor_gain	1.0000
1:153373966:TT:T	acceptor_gain	1.0000
1:153373966:TTCT:T	acceptor_loss	1.0000
1:153373967:TCT:T	acceptor_loss	1.0000
1:153373968:C:A	acceptor_loss	1.0000
1:153373968:C:CC	acceptor_gain	1.0000
1:153373969:T:G	acceptor_loss	1.0000
1:153373963:ATATT:A	acceptor_gain	0.9900
1:153373965:ATT:A	acceptor_gain	0.9900
1:153374450:CCTA:C	donor_loss	0.9900
1:153374451:CTA:C	donor_loss	0.9900
1:153374452:TAC:T	donor_loss	0.9900
1:153374453:A:AC	donor_gain	0.9900
1:153374453:A:AT	donor_loss	0.9900
1:153374454:C:CC	donor_gain	0.9900
1:153374608:TTAAC:T	acceptor_gain	0.9900
1:153374609:TAAC:T	acceptor_gain	0.9900
1:153374613:C:CC	acceptor_gain	0.9900
1:153375550:A:AC	donor_gain	0.9900
1:153375550:AC:A	donor_gain	0.9900
1:153375550:ACC:A	donor_gain	0.9900
1:153375551:C:CC	donor_gain	0.9900
1:153375551:CC:C	donor_gain	0.9900
1:153375551:CCC:C	donor_gain	0.9900
1:153375551:CCCCT:C	donor_gain	0.9900
1:153375546:ACTT:A	donor_loss	0.9800
1:153375547:CTTA:C	donor_loss	0.9800
1:153375548:TTA:T	donor_loss	0.9800
1:153375549:TA:T	donor_loss	0.9800
1:153375550:A:AG	donor_loss	0.9800

AlphaMissense

611 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153374548:G:C	F15L	0.975
1:153374548:G:T	F15L	0.975
1:153374550:A:G	F15L	0.975
1:153373884:G:C	F74L	0.950
1:153373884:G:T	F74L	0.950
1:153373886:A:G	F74L	0.950
1:153373893:A:C	F71L	0.906
1:153373893:A:T	F71L	0.906
1:153373895:A:G	F71L	0.906
1:153373900:A:T	V69D	0.880
1:153374495:A:G	L33P	0.879
1:153374549:A:G	F15S	0.875
1:153374510:A:T	L28H	0.866
1:153374486:A:G	L36P	0.856
1:153373903:T:G	Q68P	0.836
1:153373885:A:G	F74S	0.833
1:153373932:G:C	F58L	0.817
1:153373932:G:T	F58L	0.817
1:153373934:A:G	F58L	0.817
1:153374549:A:C	F15C	0.816
1:153374570:A:G	L8P	0.814
1:153374538:A:G	S19P	0.808
1:153374510:A:G	L28P	0.803
1:153373861:A:G	L82P	0.798
1:153374483:A:G	L37P	0.797
1:153374550:A:C	F15V	0.797
1:153373894:A:G	F71S	0.796
1:153374547:G:C	H16D	0.796
1:153374471:A:G	L41P	0.783
1:153374550:A:T	F15I	0.782

dbSNP variants (sampled 300 via entrez): RS1000192113 (1:153377013 C>T), RS1000369413 (1:153374624 C>G), RS1000474084 (1:153375689 AT>A), RS1002207009 (1:153374435 G>A,C), RS1002703927 (1:153376591 G>A), RS1002776951 (1:153375239 G>A,C), RS1003140114 (1:153376327 G>A), RS1003858497 (1:153376612 T>G), RS1004757084 (1:153375769 C>T), RS1006051090 (1:153374166 C>G,T), RS1006495097 (1:153373817 A>G), RS1007145094 (1:153373465 G>A), RS1007663454 (1:153374245 T>C), RS1008875306 (1:153375271 A>G), RS1009301262 (1:153376644 G>A)

Disease associations

OMIM: gene MIM:603112 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005187_1	Matrix metalloproteinase-8 levels	5.000000e-13
GCST006585_344	Blood protein levels	8.000000e-15
GCST008916_87	Asthma	2.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
Air Pollutants	affects expression, increases abundance, increases expression, decreases expression	3
Ozone	affects expression, increases abundance, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Antirheumatic Agents	decreases expression	2
triphenyl phosphate	affects expression	1
tetrachloroisophthalonitrile	increases expression	1
hydroquinone	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
miglitol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Antimony Potassium Tartrate	decreases expression	1
Arecoline	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Cycloheximide	decreases expression, decreases reaction	1
Glucose	affects binding, decreases reaction, increases reaction, increases expression	1
Methotrexate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Asbestos, Crocidolite	increases expression	1
Sodium Selenite	increases expression	1
Lactic Acid	decreases expression	1
Nanotubes, Carbon	increases expression	1

Clinical trials (associated diseases)

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