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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZDHHC23
zDHHC palmitoyltransferase 23
Chromosome 3 · 3q13.31
NCBI Gene: 254887Ensembl: ENSG00000184307.17HGNC: HGNC:28654UniProt: A0A1W2PRJ8
16PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein palmitoylationprotein localization to plasma membraneendoplasmic reticulumFuchs endothelial corneal dystrophyX-linked endothelial corneal dystrophyattention deficit hyperactivity disorderessential thrombocythemia
✦AI Summary

ZDHHC23 is a palmitoyltransferase that catalyzes S-palmitoylation of diverse protein substrates, regulating their membrane localization and function. The enzyme mediates palmitoylation of KCNMA1 to control BK channel localization to the plasma membrane 1, and in spinal astrocytes, palmitoylates GFAP to enhance inflammatory factor secretion and pain signaling 2. ZDHHC23 also palmitoylates PHF2, promoting its ubiquitin-dependent degradation and consequently activating lipogenic pathways in hepatocellular carcinoma 3, and mediates T-bet palmitoylation to regulate Th1 cell differentiation in gastric cancer 4. Pan-cancer analysis identifies ZDHHC23 among palmitoylation-related genes dysregulated by oncogenic Myc signaling, with contributions to mTOR signaling, DNA repair, and immune pathways that influence tumorigenesis and immunotherapy response 5. In glioblastoma, ZDHHC23 competes with ZDHHC18 for interaction with the E3 ligase RNF144A to regulate BMI1 polyubiquitination, controlling glioma stem cell plasticity 6. ZDHHC23 expression correlates with esophageal cancer radiosensitivity through miRNA-mRNA regulatory networks 7 and associates with white blood cell counts in acute lymphoblastic leukemia 8, suggesting broader roles in cancer biology and hematologic malignancies.

Sources cited
1
ZDHHC23 mediates palmitoylation of PHF2, enhancing its ubiquitin-dependent degradation and regulating SREBP1c-dependent lipogenesis in hepatocellular carcinoma
PMID: 37828054
2
ZDHHC23 is identified as a significant contributor to mTOR signaling, DNA repair, and immune pathways in pan-cancer analysis of palmitoylation dysregulation
PMID: 37978524
3
ZDHHC23 mediates GFAP palmitoylation in spinal astrocytes, promoting inflammatory factor secretion and neuropathic pain development
PMID: 38050183
4
ZDHHC23 competitively interacts with RNF144A E3 ligase to regulate BMI1 polyubiquitination and control glioma stem cell plasticity
PMID: 30658672
5
ZDHHC23 mediates T-bet palmitoylation, promoting its degradation and inhibiting Th1 cell differentiation in gastric cancer
PMID: 39989253
6
ZDHHC23 catalyzes S-acylation of BK channel α-subunit S0-S1 loop, controlling functional coupling with β1-subunits
PMID: 31213527
7
ZDHHC23 is part of miR-132-3p/CAND1/ZDHHC23 pathway associated with esophageal cancer radiosensitivity
PMID: 36456979
8
ZDHHC23 is differentially expressed based on white blood cell count in B-precursor acute lymphoblastic leukemia
PMID: 27536776
Disease Associationsⓘ20
Fuchs endothelial corneal dystrophyOpen Targets
0.06Suggestive
X-linked endothelial corneal dystrophyOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
essential thrombocythemiaOpen Targets
0.05Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.05Suggestive
granular corneal dystrophy type IOpen Targets
0.05Suggestive
congenital hereditary endothelial dystrophy of corneaOpen Targets
0.05Suggestive
Cataract-microcornea syndromeOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
posterior polymorphous corneal dystrophyOpen Targets
0.05Suggestive
gliomaOpen Targets
0.04Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.04Suggestive
macular corneal dystrophyOpen Targets
0.04Suggestive
Peters anomalyOpen Targets
0.04Suggestive
Thiel-Behnke corneal dystrophyOpen Targets
0.04Suggestive
corneal endothelial dystrophyOpen Targets
0.04Suggestive
Central cloudy dystrophy of FrancoisOpen Targets
0.04Suggestive
central cloudy dystrophy of FrançoisOpen Targets
0.04Suggestive
Schnyder corneal dystrophyOpen Targets
0.04Suggestive
granular corneal dystrophy type IIOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZDHHC22Protein interaction84%ZDHHC4Shared pathway50%ZDHHC3Shared pathway33%GOLGA7BShared pathway33%NACA2Shared pathway33%WDR72Shared pathway33%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
91%
Lung
31%
Brain
26%
Heart
21%
Ovary
19%
Gene Interaction Network
Click a node to explore
ZDHHC23ZDHHC22ZDHHC4ZDHHC3GOLGA7BNACA2WDR72
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IYP9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.28LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.98 [0.77–1.28]
RankingsWhere ZDHHC23 stands among ~20K protein-coding genes
  • #15,447of 20,598
    Most Researched16
  • #13,462of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedZDHHC23
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma.
PMID: 37828054
Nat Commun · 2023
1.00
2
Palmitoylation landscapes across human cancers reveal a role of palmitoylation in tumorigenesis.
PMID: 37978524
J Transl Med · 2023
0.90
3
GFAP palmitoylcation mediated by ZDHHC23 in spinal astrocytes contributes to the development of neuropathic pain.
PMID: 38050183
Reg Anesth Pain Med · 2024
0.80
4
DHHC protein family targets different subsets of glioma stem cells in specific niches.
PMID: 30658672
J Exp Clin Cancer Res · 2019
0.70
5
Methionine Restriction Exerts Anti-Tumor Immunity via Joint Intervention of T-Bet Palmitoylation in Gastric Cancer.
PMID: 39989253
Biotechnol J · 2025
0.60