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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZC3H12A
zinc finger CCCH-type containing 12A
Chromosome 1 · 1p34.3
NCBI Gene: 80149Ensembl: ENSG00000163874.11HGNC: HGNC:26259UniProt: A0A1W2PQC8
125PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of p38MAPK cascadenegative regulation of tumor necrosis factor productionnegative regulation of macrophage activationnegative regulation of nitric oxide biosynthetic processneurodegenerative diseasemathematical abilityphobic disordermajor depressive disorder
✦AI Summary

ZC3H12A is a zinc finger CCCH-type protein that functions as a negative regulator of inflammatory and immune responses. Mechanistically, ZC3H12A operates through mRNA destabilization and miRNA catabolism, suppressing NF-κB signaling and IL-6 production 1. The protein exhibits antiviral activity by decreasing HIV-1 viral RNA abundance in lymphocytes and restrains mucosal inflammation in IBD by orchestrating macrophage differentiation 2. ZC3H12A's disease relevance is particularly significant in inflammatory bowel disease, where mutations are positively selected in inflamed epithelium 34. The selection of ZC3H12A-mutant cells in ulcerative colitis suggests protective effects against chr1 inflammation 4. Clinically, ZC3H12A emerges as a therapeutic target for T cell engineering. ZC3H12A deficiency promotes stemness in exhausted CD8+ T cells when combined with BCOR ablation, enhancing viral control and immune function 5. Additionally, ZC3H12A loss confers early growth advantages to CAR T cells in multiple myeloma, improving tumor clearance and survival 6. These findings position ZC3H12A inhibition as a promising strategy for adoptive immunotherapy in cancer and chr1 viral infections.

Sources cited
1
IL-6 is a pleiotropic cytokine with roles in immunity and excessive production contributes to disease pathology
PMID: 30995492
2
ZC3H12A mutations are under positive selection in IBD-affected colon and may play a causal role in IBD pathogenesis
PMID: 32697969
3
REGNASE-1 (ZC3H12A) targeting reprograms CD8+ T cells to long-lived effector cells with improved persistence and efficacy
PMID: 31827283
4
MCPIP1 (ZC3H12A ortholog) restrains mucosal inflammation and regulates intestinal macrophage differentiation in IBD
PMID: 37015751
5
ZC3H12A deficiency initiates stemness program in exhausted T cells; co-targeting BCOR and ZC3H12A enhances TPEX function and viral control
PMID: 40327039
6
ZC3H12A mutations are positively selected in ulcerative colitis epithelium and implicated in downregulation of pro-inflammatory IL-17 signals
PMID: 31853061
7
ZC3H12A loss confers early growth advantages to CAR T cells in vivo, enhancing tumor clearance and survival in multiple myeloma
PMID: 40993381
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.24Weak
mathematical abilityOpen Targets
0.22Weak
phobic disorderOpen Targets
0.20Weak
major depressive disorderOpen Targets
0.18Weak
parasitic infectionOpen Targets
0.16Weak
neoplasmOpen Targets
0.12Weak
experimental autoimmune encephalomyelitisOpen Targets
0.09Suggestive
microphthalmia with limb anomaliesOpen Targets
0.08Suggestive
neuroblastomaOpen Targets
0.08Suggestive
inflammatory bowel diseaseOpen Targets
0.08Suggestive
anemiaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
pterygiumOpen Targets
0.08Suggestive
hidradenitis suppurativaOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
cervical cancerOpen Targets
0.07Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
pulmonary arterial hypertensionOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRAF6Protein interaction99%IL6Protein interaction99%IL1BProtein interaction97%TANKProtein interaction96%REG1AProtein interaction89%REG1BProtein interaction89%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
63%
Liver
24%
Ovary
8%
Heart
5%
Brain
1%
Gene Interaction Network
Click a node to explore
ZC3H12ATRAF6IL6IL1BTANKREG1AREG1B
PROTEIN STRUCTURE
Preparing viewer…
PDB3V32 · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.44Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.25 [0.15–0.44]
RankingsWhere ZC3H12A stands among ~20K protein-coding genes
  • #3,781of 20,598
    Most Researched125 · top quartile
  • #2,395of 17,882
    Most Constrained (LOEUF)0.44 · top quartile
Genes detectedZC3H12A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Targeting Interleukin-6 Signaling in Clinic.
PMID: 30995492
Immunity · 2019
1.00
2
Somatic Evolution in Non-neoplastic IBD-Affected Colon.
PMID: 32697969
Cell · 2020
0.90
3
Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy.
PMID: 31827283
Nature · 2019
0.80
4
MCPIP1 restrains mucosal inflammation by orchestrating the intestinal monocyte to macrophage maturation via an ATF3-AP1S2 axis.
PMID: 37015751
Gut · 2023
0.70
5
BCOR and ZC3H12A suppress a core stemness program in exhausted CD8+ T cells.
PMID: 40327039
J Exp Med · 2025
0.60