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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZDHHC2
zDHHC palmitoyltransferase 2
Chromosome 8 · 8p22
NCBI Gene: 51201Ensembl: ENSG00000104219.14HGNC: HGNC:18469UniProt: A0A140VKD9
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
palmitoyltransferase activityprotein-cysteine S-palmitoyltransferase activityprotein homodimerization activitysynapse assemblyschizophreniaCOVID-19neoplasmgastric cancer
✦AI Summary

ZDHHC2 (zDHHC palmitoyltransferase 2) is a member of the DHHC protein family that catalyzes S-palmitoylation, a post-translational modification involving the attachment of palmitic acid to cysteine residues 1. This enzyme exhibits diverse substrate specificity, palmitoylating proteins including GSDME during chemotherapy-induced pyroptosis 1, Gpm6a to maintain mammary stem cell activity 2, USP19 to regulate ferroptosis in prostate cancer 3, and viral proteins such as influenza A hemagglutinin and M2 4. ZDHHC2 localizes to multiple cellular compartments including the endoplasmic reticulum, Golgi apparatus, and plasma membrane, facilitating protein targeting to membrane rafts and regulating synaptic function 5. The gene functions as a tumor suppressor, with reduced expression associated with metastasis and poor prognosis in hepatocellular carcinoma 6 and gastric adenocarcinoma 7. ZDHHC2 also plays critical roles in immune regulation, being essential for plasmacytoid dendritic cell-mediated inflammatory responses in psoriasis through IRF7 regulation 8. Additionally, genetic variants in ZDHHC2 are associated with schizophrenia risk in Han Chinese populations, likely affecting synaptic plasticity through PSD-95 and AKAP79/150 palmitoylation 5.

Sources cited
1
ZDHHC2 palmitoylates GSDME during chemotherapy-induced pyroptosis
PMID: 32332857
2
ZDHHC2 palmitoylates Gpm6a to maintain mammary stem cell activity
PMID: 39321020
3
ZDHHC2 palmitoylates USP19 to regulate ferroptosis in prostate cancer
PMID: 41126755
4
ZDHHC2 palmitoylates influenza A hemagglutinin and M2 proteins
PMID: 31872235
5
ZDHHC2 functions as tumor suppressor in hepatocellular carcinoma
PMID: 24995331
6
Reduced ZDHHC2 expression associated with poor prognosis in gastric adenocarcinoma
PMID: 23457560
7
ZDHHC2 essential for plasmacytoid dendritic cell inflammatory responses in psoriasis
PMID: 33488612
8
ZDHHC2 variants associated with schizophrenia risk through synaptic plasticity regulation
PMID: 32180374
Disease Associationsⓘ20
schizophreniaOpen Targets
0.46Moderate
COVID-19Open Targets
0.38Weak
neoplasmOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
psoriasisOpen Targets
0.06Suggestive
gamma chain deficiencyOpen Targets
0.05Suggestive
X-linked lymphoproliferative diseaseOpen Targets
0.05Suggestive
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 18Open Targets
0.05Suggestive
MODYOpen Targets
0.05Suggestive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.05Suggestive
combined immunodeficiency due to moesin deficiencyOpen Targets
0.05Suggestive
gastric adenocarcinomaOpen Targets
0.05Suggestive
agammaglobulinemia 7, autosomal recessiveOpen Targets
0.05Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.05Suggestive
hyper-IgE recurrent infection syndrome 5, autosomal recessiveOpen Targets
0.05Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CKAP4Protein interaction93%GOLGA7Protein interaction76%ZDHHC7Shared pathway24%ZDHHC15Shared pathway23%ZDHHC14Shared pathway20%ZDHHC3Shared pathway19%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
96%
Heart
50%
Lung
35%
Ovary
32%
Liver
19%
Gene Interaction Network
Click a node to explore
ZDHHC2CKAP4GOLGA7ZDHHC7ZDHHC15ZDHHC14ZDHHC3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UIJ5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.40LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.07 [0.84–1.40]
RankingsWhere ZDHHC2 stands among ~20K protein-coding genes
  • #12,486of 20,598
    Most Researched28
  • #14,459of 17,882
    Most Constrained (LOEUF)1.40
Genes detectedZDHHC2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate.
PMID: 32332857
Cell Death Dis · 2020
1.00
2
Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation is essential for maintenance of mammary stem cell activity.
PMID: 39321020
Cell Rep · 2024
0.90
3
ZDHHC2-Dependent Palmitoylation Dictates Ferroptosis and Castration Sensitivity in Prostate Cancer via Controlling ACSL4 Degradation and Lipid Peroxidation.
PMID: 41126755
Adv Sci (Weinh) · 2026
0.80
4
A critical role for ZDHHC2 in metastasis and recurrence in human hepatocellular carcinoma.
PMID: 24995331
Biomed Res Int · 2014
0.70
5
Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis.
PMID: 33488612
Front Immunol · 2020
0.60