ZDHHC8
Chr 22zDHHC palmitoyltransferase 8
Also known as: DHHC8, ZDHHCL1, ZNF378
The protein functions as a palmitoyltransferase that adds palmitate to various protein substrates, including ABCA1 (regulating cholesterol transport) and potentially the D2 dopamine receptor, thereby controlling their plasma membrane localization and function. Mutations in this gene may be associated with susceptibility to schizophrenia, though definitive pediatric neurological phenotypes are not well-established. The gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.37), suggesting that complete loss of function is likely deleterious.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
499 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 305 | 0 | 305 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 0 | 151 | 9 | 0 | 160 |
Likely Benign | 0 | 6 | 0 | 2 | 8 |
Benign | 0 | 0 | 3 | 0 | 3 |
| Total | 0 | 157 | 326 | 2 | 485 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZDHHC8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools