ZDHHC8 (Zinc Finger DHHC-Type Palmitoyltransferase 8)
A palmitoyltransferase implicated in neurodevelopmental disorders and cancer
Gene Information Card
| Symbol | ZDHHC8 |
|---|---|
| Full Name | Zinc Finger DHHC-Type Palmitoyltransferase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 29801 ncbi.nlm.nih.gov/gene/29801 |
| Ensembl ID | ENSG00000197969 |
| UniProt ID | Q9ULC8 |
| OMIM ID | 608784 |
| HGNC ID | 18474 |
| Aliases | DHHC8, ZNF300, FLJ12689 |
Description
ZDHHC8 encodes a member of the DHHC family of palmitoyltransferases, which catalyze the addition of palmitate to cysteine residues of target proteins. This post-translational modification regulates protein trafficking, membrane localization, and signaling. ZDHHC8 is highly expressed in the brain and is involved in neuronal development and synaptic function. It is located in the 22q11.2 region, a locus frequently deleted in DiGeorge syndrome and associated with psychiatric disorders. ZDHHC8 has also been implicated in cancer, where its expression can affect tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 22q11.2 Deletion Syndrome | Haploinsufficiency of ZDHHC8 due to microdeletion contributes to neurodevelopmental phenotypes, including cognitive deficits and psychiatric disorders. | ClinVar, OMIM |
| Schizophrenia | Reduced ZDHHC8 expression or function may impair glutamatergic signaling and dendritic spine maintenance, increasing risk. | PMID: 15345707, OMIM |
| Intellectual Disability | Loss of ZDHHC8 palmitoyltransferase activity disrupts neuronal protein palmitoylation, affecting synaptic plasticity and cognition. | ClinVar, PMID: 19015237 |
| Cancer (e.g., breast, lung) | Altered ZDHHC8 expression can modulate palmitoylation of oncogenic proteins, influencing cell proliferation and metastasis. | COSMIC, PMID: 29211733 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 25.3 | High |
| Testis | 12.1 | Medium |
| Lung | 8.4 | Medium |
| Liver | 5.2 | Low |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.5 | High expression; used in neurodevelopment studies |
| HeLa (cervical carcinoma) | 9.2 | Moderate expression |
| A549 (lung carcinoma) | 7.8 | Moderate expression |
| MCF7 (breast carcinoma) | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs175174 | SNP (intronic) | ~20% allele frequency | Associated with schizophrenia risk in some populations; may affect splicing |
| c.1042C>T (p.Arg348Ter) | Nonsense | Rare | Loss of function; likely pathogenic |
| c.1255G>A (p.Gly419Arg) | Missense | Rare | Uncertain significance; may affect catalytic activity |
| c.1114_1115del (p.Leu372fs) | Frameshift | Rare | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that reduce ZDHHC8 protein levels or catalytic activity are associated with neurodevelopmental phenotypes.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression in some cancers may promote oncogenic signaling.
Dominant Negative (DN)
Not well characterized; some missense mutations may interfere with enzyme dimerization or substrate binding.
View complete mutation data：
Gene Ontology (GO)
| • protein palmitoyltransferase activity (GO:0008276) | • palmitoyltransferase activity (GO:0016409) |
| • plasma membrane (GO:0005886) | • Golgi apparatus (GO:0005794) |
| • synapse (GO:0045202) | • integral component of membrane (GO:0016021) |
Pathways
• Protein palmitoylation
• RAS signaling
• Glutamatergic synapse
• Dendritic spine morphogenesis
Protein Summary
ZDHHC8 is a 765-amino acid protein with a conserved DHHC (Asp-His-His-Cys) domain essential for palmitoyltransferase activity. It localizes to the Golgi and plasma membrane, where it palmitoylates substrates such as neuronal proteins (e.g., PSD-95, GRIN2A) and signaling molecules (e.g., RAS). In the brain, ZDHHC8 regulates synaptic plasticity and dendritic spine density. Its dysfunction is linked to psychiatric and neurodevelopmental disorders. In cancer, ZDHHC8 can modulate oncogenic pathways, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZDHHC8 Knockout HEK293 Cell Line | EDJ-KQ9051 | Human | 29801 | Details Get a Quote |
| ZDHHC8 Knockout A-549 Cell Line | EDJ-KQ35504 | Human | 29801 | Details Get a Quote |
| ZDHHC8 Knockout HCT 116 Cell Line | EDJ-KQ35505 | Human | 29801 | Details Get a Quote |
| ZDHHC8 Knockout HeLa Cell Line | EDJ-KQ35506 | Human | 29801 | Details Get a Quote |
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