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6 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZNF396
zinc finger protein 396
Chromosome 18 · 18q12.2
NCBI Gene: 252884Ensembl: ENSG00000186496.13HGNC: HGNC:18824UniProt: Q96N95
17PubMed Papers
14Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingnucleuschromatinDNA-binding transcription factor activity, RNA polymerase II-specificIncreased total eosinophil countmathematical abilityCachexiarespiratory tract infectious disorder
✦AI Summary

ZNF396 (zinc finger protein 396) is a SCAN domain-containing transcription factor located on chromosome 18 that functions primarily as a DNA-dependent transcriptional repressor 1. The gene produces multiple isoforms through alternative splicing, with the full-length isoform (ZNF396-fu) containing a SCAN domain and C2H2 zinc finger repeats that enable sequence-specific DNA binding and nuclear localization, while the truncated isoform (ZNF396-nf) contains only the SCAN domain and exhibits diffuse cytoplasmic distribution 1. ZNF396 can form homo- and hetero-associations with related proteins and demonstrates transcriptional repression activity 1. In basal cell carcinoma, ZNF396 is highly expressed in tumor cells where it represses Notch signaling, particularly by suppressing Hes1 expression, thereby preventing differentiation and maintaining the stem/progenitor phenotype; siRNA silencing of ZNF396 induces Notch2, Hes1, and involucrin expression and inhibits BCC cell proliferation 2. ZNF396 is also upregulated in response to adaptogenic herbal extracts and stress-response signaling in neuronal cells, implicating it in cellular stress adaptation 3. Additionally, ZNF396 has been associated with Parkinson's disease susceptibility in genome-wide association studies of Chinese populations 4. The gene was examined as a candidate locus in alopecia with mental retardation syndrome mapping but showed no disease-causing variants in affected individuals 5.

Sources cited
1
ZNF396 is a SCAN domain-containing gene with multiple isoforms produced by alternative splicing; isoforms contain C2H2 zinc finger repeats and exhibit transcriptional repression activity
PMID: 12801647
2
ZNF396 is expressed in basal cell carcinoma nuclei, represses Notch-Hes1 signaling to prevent differentiation, and its silencing inhibits BCC cell proliferation
PMID: 24445935
3
ZNF396 is upregulated in brain cells upon treatment with adaptogenic herbal extracts and is involved in adaptive stress-response signaling pathways
PMID: 30466987
4
ZNF396 is associated with sporadic Parkinson's disease susceptibility in genome-wide association studies of Han Chinese populations
PMID: 26227905
5
ZNF396 was examined as a candidate gene in alopecia with mental retardation syndrome mapping but showed no disease-causing sequence variants
PMID: 17451405
Disease Associationsⓘ14
Increased total eosinophil countOpen Targets
0.31Weak
mathematical abilityOpen Targets
0.20Weak
CachexiaOpen Targets
0.18Weak
respiratory tract infectious disorderOpen Targets
0.02Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
basal cell carcinomaOpen Targets
0.01Suggestive
skin basal cell carcinomaOpen Targets
0.01Suggestive
ThymomaOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.00Suggestive
squamous cell carcinomaOpen Targets
0.00Suggestive
colon adenocarcinomaOpen Targets
0.00Suggestive
colorectal adenocarcinomaOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
uterine corpus endometrial carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZKSCAN4Protein interaction84%ZNF24Protein interaction83%ZSCAN20Protein interaction83%ZNF174Protein interaction83%ZKSCAN8Protein interaction83%SCAND1Protein interaction83%
Tissue Expression6 tissues
Brain
100%
Liver
86%
Ovary
76%
Lung
71%
Heart
65%
Bone Marrow
34%
Gene Interaction Network
Click a node to explore
ZNF396ZKSCAN4ZNF24ZSCAN20ZNF174ZKSCAN8SCAND1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96N95
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.64 [0.42–1.00]
RankingsWhere ZNF396 stands among ~20K protein-coding genes
  • #15,180of 20,598
    Most Researched17
  • #9,621of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedZNF396
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
A Pooling Genome-Wide Association Study Combining a Pathway Analysis for Typical Sporadic Parkinson's Disease in the Han Population of Chinese Mainland.
PMID: 26227905
Mol Neurobiol · 2016
1.00
2
Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.
PMID: 30466987
Phytomedicine · 2018
0.83
3
Mapping of a gene for alopecia with mental retardation syndrome (APMR3) on chromosome 18q11.2-q12.2.
PMID: 17451405
Ann Hum Genet · 2007
0.67
4
Zinc finger and SCAN domain-containing protein 18 is a potential DNA methylation-modified tumor suppressor and biomarker in breast cancer.
PMID: 37223020
Front Endocrinol (Lausanne) · 2023
0.50
5
Expression of ZNF396 in basal cell carcinoma.
PMID: 24445935
Arch Dermatol Res · 2014
0.33