S100A12 (Calgranulin C) Gene
S100 Calcium Binding Protein A12: Role in Inflammation, Innate Immunity, and Disease
Gene Information Card
| Symbol | S100A12 |
|---|---|
| Full Name | S100 calcium binding protein A12 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 6283 ncbi.nlm.nih.gov/gene/6283 |
| Ensembl ID | ENSG00000163221 |
| UniProt ID | P80511 |
| OMIM ID | 603112 |
| HGNC ID | 10489 |
| Aliases | CAGC, CGRP, EN-RAGE, MRP-6, p6 |
Description
S100A12 (calgranulin C) is a member of the S100 family of calcium-binding proteins. It is primarily expressed in neutrophils and monocytes and functions as a damage-associated molecular pattern (DAMP) molecule. S100A12 binds calcium and zinc, and upon secretion, activates the receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4), promoting pro-inflammatory cytokine release and chemotaxis. It plays a key role in innate immune responses and is implicated in chronic inflammatory disorders, including inflammatory bowel disease, rheumatoid arthritis, and vasculitis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory Bowel Disease (IBD) | Elevated S100A12 in serum and feces; acts as a DAMP activating RAGE/TLR4, driving intestinal inflammation | ClinVar, NCBI Gene, multiple studies |
| Rheumatoid Arthritis | S100A12 is overexpressed in synovial fluid and tissue; promotes neutrophil recruitment and joint inflammation via RAGE signaling | NCBI Gene, OMIM |
| Kawasaki Disease | Increased serum S100A12 correlates with coronary artery inflammation; serves as a biomarker for disease activity | ClinVar, literature |
| Cystic Fibrosis | S100A12 levels elevated in airway secretions; contributes to neutrophil-dominated inflammation and tissue damage | NCBI Gene, studies |
| Type 1 Diabetes | S100A12 implicated in islet inflammation and beta-cell damage through RAGE activation | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 124.8 | High |
| Spleen | 78.3 | High |
| Lung | 45.6 | Medium |
| Small Intestine | 32.1 | Medium |
| Colon | 28.9 | Medium |
| Whole Blood | 22.4 | Medium |
| Liver | 5.2 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Neutrophils | High | Primary cell type; highest expression |
| Monocytes | Medium | Constitutive expression |
| Macrophages | Low | Induced upon activation |
| THP-1 (monocytic leukemia) | Medium | Model for monocyte expression |
| HL-60 (promyelocytic leukemia) | High | Differentiation-dependent expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.133G>A (p.Glu45Lys) | Missense | <0.01% | Unknown; rare variant in population databases |
| c.226C>T (p.Arg76Cys) | Missense | <0.01% | Unknown; rare variant in population databases |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in S100A12.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in S100A12.
Dominant Negative (DN)
No dominant-negative mutations described for S100A12.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAGE signaling pathway (Reactome: R-HSA-193648)
• TLR4 signaling cascade (Reactome: R-HSA-166020)
• Innate Immune System (Reactome: R-HSA-168249)
• S100 proteins (WikiPathways: WP509)
Protein Summary
S100A12 is a 92-amino acid calcium- and zinc-binding protein (UniProt P80511) that forms homodimers. It is secreted by activated neutrophils and monocytes and acts as a pro-inflammatory DAMP. Upon binding to RAGE and TLR4, it activates NF-κB and MAPK pathways, leading to cytokine production (e.g., TNF-α, IL-1β, IL-6) and chemotaxis. S100A12 also exhibits antimicrobial activity through zinc chelation. Its expression is tightly regulated and elevated in various inflammatory diseases, making it a potential biomarker and therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| S100A12 Knockout HEK293 Cell Line | EDJ-KQ5704 | Human | 6283 | Details Get a Quote |
| S100A12 Knockout HeLa Cell Line | EDJ-KQ54381 | Human | 6283 | Details Get a Quote |
| S100A12 Knockout A-549 Cell Line | EDJ-KQ62874 | Human | 6283 | Details Get a Quote |
| S100A12 Knockout HCT 116 Cell Line | EDJ-KQ71340 | Human | 6283 | Details Get a Quote |
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