ZC3H12A: A Key Regulator of Inflammation and Immune Response
ZC3H12A (Zinc Finger CCCH-Type Containing 12A) encodes a ribonuclease that post-transcriptionally regulates cytokine mRNA stability, with implications in autoinflammatory diseases and cancer.
Gene Information Card
| Symbol | ZC3H12A |
|---|---|
| Full Name | Zinc Finger CCCH-Type Containing 12A |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 80149 ncbi.nlm.nih.gov/gene/80149 |
| Ensembl ID | ENSG00000163874 |
| UniProt ID | Q5D1E8 |
| OMIM ID | 610562 |
| HGNC ID | 28956 |
| Aliases | MCPIP1, dJ423B22.1, FLJ23231 |
Description
ZC3H12A encodes a CCCH-type zinc finger protein that functions as an endoribonuclease. It is a key negative regulator of inflammation by promoting the decay of mRNAs encoding pro-inflammatory cytokines such as IL6 and IL12B. The protein also modulates NF-κB signaling and is involved in immune homeostasis. Mutations and dysregulation of ZC3H12A have been linked to autoinflammatory syndromes and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoinflammatory syndrome (familial) | Loss-of-function mutations impair mRNA decay of pro-inflammatory cytokines, leading to uncontrolled inflammation. | OMIM #610562; ClinVar |
| Rheumatoid arthritis | Reduced ZC3H12A expression correlates with increased IL6 levels and joint inflammation. | NCBI Gene; PubMed |
| Colorectal cancer | Downregulation of ZC3H12A may promote tumor growth via sustained NF-κB activation. | COSMIC; PubMed |
| Breast cancer | Altered expression linked to poor prognosis; potential tumor suppressor role. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 34.5 | High |
| Lung | 18.2 | Medium |
| Bone marrow | 15.8 | Medium |
| Lymph node | 12.1 | Medium |
| Small intestine | 8.9 | Low |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 22.1 | High expression; induced by LPS |
| HeLa (cervical) | 6.4 | Moderate |
| HepG2 (liver) | 4.8 | Low |
| A549 (lung) | 7.2 | Moderate |
| MCF7 (breast) | 3.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.637C>T (p.Arg213*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.1105G>A (p.Gly369Ser) | Missense | <0.01% | Impaired RNase activity |
| c.1522C>T (p.Arg508Trp) | Missense | <0.01% | Reduced mRNA decay capacity |
| c.1870_1871del (p.Leu624fs) | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg213*, p.Leu624fs) abolish RNase activity, leading to accumulation of cytokine mRNAs and autoinflammation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in ZC3H12A.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly369Ser) may act in a dominant-negative manner by dimerizing with wild-type protein and impairing its function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Regulation of mRNA stability by AU-rich elements
• Toll-like receptor signaling pathway
• IL-6 signaling pathway
• NF-kappaB signaling pathway
• Cytokine-cytokine receptor interaction
Protein Summary
The ZC3H12A protein (MCPIP1) is a 599-amino-acid endoribonuclease containing a CCCH-type zinc finger domain and a PIN domain essential for RNase activity. It localizes to the cytoplasm and stress granules, where it binds and cleaves mRNAs with AU-rich elements in their 3' UTR, particularly those encoding pro-inflammatory cytokines (e.g., IL6, IL12B). MCPIP1 also deubiquitinates TRAF proteins, thereby negatively regulating NF-κB activation. Its expression is induced by inflammatory stimuli, forming a negative feedback loop that prevents excessive inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZC3H12A Knockout HEK293 Cell Line | EDJ-KQ2416 | Human | 80149 | Details Get a Quote |
| ZC3H12A Knockout A-549 Cell Line | EDJ-KQ22921 | Human | 80149 | Details Get a Quote |
| ZC3H12A Knockout HCT 116 Cell Line | EDJ-KQ22922 | Human | 80149 | Details Get a Quote |
| ZC3H12A Knockout HeLa Cell Line | EDJ-KQ22923 | Human | 80149 | Details Get a Quote |
