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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZACN
zinc activated ion channel
Chromosome 17 · 17q25.1
NCBI Gene: 353174Ensembl: ENSG00000186919.13HGNC: HGNC:29504UniProt: Q401N2
12PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to zinc ionmonoatomic ion transmembrane transportligand-gated monoatomic ion channel activityplasma membraneatrial heart septal defectneurodevelopmental disorder with seizures and brain atrophycervical cancerinfection
✦AI Summary

ZACN (zinc activated ion channel) encodes a ligand-gated cation channel that facilitates the movement of sodium and potassium ions across cell membranes when activated by zinc (Zn2+), copper (Cu2+), and pH changes 1. The channel may also transport cesium and exhibits evolutionary conservation across mammalian species, suggesting physiological importance 1. ZACN functions as a homomeric cation-selective channel with robust responses to zinc (10 mM) and acidic pH (4.0) 1. The gene shows tissue-specific expression patterns and has been implicated in various pathological conditions. In cancer contexts, ZACN expression is altered in hypopharyngeal squamous cell carcinoma, where it serves as a hub protein in protein-protein interaction networks 2. In kidney renal clear cell carcinoma, high ZACN expression correlates with poor prognosis and promotes cell proliferation by inhibiting alkaliptosis, a specific form of cell death 3. Additionally, ZACN is involved in vocal fold responses to dehydration, being upregulated during surface dehydration challenges 4. Clinical significance includes its potential as a prognostic biomarker in renal cancer and its involvement in fusion-negative phosphaturic mesenchymal tumors through FN1::ZACN fusion events 5.

Sources cited
1
ZACN encodes a ligand-gated cation channel activated by zinc, copper, and pH changes, with evolutionary conservation across mammals
PMID: 37745686
2
ZACN serves as a hub protein in hypopharyngeal squamous cell carcinoma protein interaction networks
PMID: 29916534
3
High ZACN expression correlates with poor prognosis in kidney renal clear cell carcinoma and promotes proliferation by inhibiting alkaliptosis
PMID: 39937414
4
ZACN is upregulated in vocal folds during surface dehydration challenges
PMID: 33308144
5
ZACN participates in fusion events (FN1::ZACN) in fusion-negative phosphaturic mesenchymal tumors
PMID: 37742927
Disease Associationsⓘ20
atrial heart septal defectOpen Targets
0.21Weak
neurodevelopmental disorder with seizures and brain atrophyOpen Targets
0.12Weak
cervical cancerOpen Targets
0.08Suggestive
infectionOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
cervical carcinomaOpen Targets
0.05Suggestive
Parkinson diseaseOpen Targets
0.05Suggestive
human papilloma virus infectionOpen Targets
0.05Suggestive
metabolic syndromeOpen Targets
0.05Suggestive
congenital heart diseaseOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
growth hormone-producing pituitary gland neoplasmOpen Targets
0.03Suggestive
non-functioning pituitary adenomaOpen Targets
0.03Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.02Suggestive
COVID-19Open Targets
0.02Suggestive
Pituitary Gland AdenomaOpen Targets
0.02Suggestive
cervical squamous intraepithelial neoplasiaOpen Targets
0.02Suggestive
vulvar intraepithelial neoplasiaOpen Targets
0.01Suggestive
anogenital venereal wartOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GALR2Protein interaction82%EXOC7Protein interaction79%LASP1Shared pathway50%SFXN2Shared pathway40%SFXN4Shared pathway40%ANO10Shared pathway40%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
57%
Liver
17%
Ovary
12%
Lung
12%
Heart
0%
Gene Interaction Network
Click a node to explore
ZACNGALR2EXOC7LASP1SFXN2SFXN4ANO10
PROTEIN STRUCTURE
Preparing viewer…
PDB8YX7 · 2.80 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.64LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.30 [1.04–1.64]
RankingsWhere ZACN stands among ~20K protein-coding genes
  • #16,623of 20,598
    Most Researched12
  • #15,859of 17,882
    Most Constrained (LOEUF)1.64
Genes detectedZACN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Somatic Mosaicism Patterns Define Clinical-Surgical Subtypes of Focal Cortical Dysplasia Through Cell-Type-Specific Expression.
PMID: 41282912
medRxiv · 2025
1.00
2
Klotho Overexpression Is Frequently Associated With Upstream Rearrangements in Fusion-Negative Phosphaturic Mesenchymal Tumors of Bone and Sinonasal Tract.
PMID: 37742927
Mod Pathol · 2023
0.90
3
RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge.
PMID: 33308144
BMC Genomics · 2020
0.80
4
Aberrantly expressed genes and miRNAs in human hypopharyngeal squamous cell carcinoma based on RNA‑sequencing analysis.
PMID: 29916534
Oncol Rep · 2018
0.70
5
Evolutionary conservation of Zinc-Activated Channel (ZAC) functionality in mammals: a range of mammalian ZACs assemble into cell surface-expressed functional receptors.
PMID: 37745686
Front Mol Biosci · 2023
0.60