ZDHHC2
Chr 8zDHHC palmitoyltransferase 2
Also known as: DHHC2, ZNF372
The protein is a palmitoyltransferase that adds palmitate to various protein substrates, playing critical roles in synaptic plasticity, protein trafficking to membranes, and G protein-coupled receptor signaling in neurons. Biallelic mutations in this highly constrained gene (LOEUF 0.69) cause autosomal recessive intellectual disability with seizures and distinctive facial features, with onset typically in infancy or early childhood. The gene shows strong intolerance to loss-of-function variants, indicating that normal protein function is essential for neurodevelopment.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-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.
ClinVar Variant Classifications
167 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 | 76 | 0 | 76 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 54 | 9 | 0 | 63 |
Likely Benign | 0 | 2 | 0 | 2 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 56 | 89 | 2 | 147 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZDHHC2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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