ZDHHC8

Chr 22

zDHHC palmitoyltransferase 8

Also known as: DHHC8, ZDHHCL1, ZNF378

NCBI Gene: 29801ENSG00000099904UniProt: Q9ULC8

This gene encodes a four transmembrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein may function as a palmitoyltransferase. Defects in this gene may be associated with a susceptibility to schizophrenia. Alternate splicing of this gene results in multiple transcript variants. A pseudogene of this gene is found on chromosome 22.[provided by RefSeq, May 2010]

559
ClinVar variants
374
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— ZDHHC8
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
374 Pathogenic / Likely Pathogenic· 161 VUS of 559 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.853
Z-score 4.06
OE 0.18 (0.09–0.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.85Z-score
OE missense 0.77 (0.71–0.84)
403 obs / 522.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.09–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.71–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 5 / 28.3Missense obs/exp: 403 / 522.1Syn Z: -1.53

ClinVar Variant Classifications

559 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic365
Likely Pathogenic9
VUS161
Likely Benign7
Benign3
365
Pathogenic
9
Likely Pathogenic
161
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
365
0
365
Likely Pathogenic
0
0
9
0
9
VUS
0
150
11
0
161
Likely Benign
0
6
0
1
7
Benign
0
0
3
0
3
Total01563881545

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AMPKα1-mediated ZDHHC8 phosphorylation promotes the palmitoylation of SLC7A11 to facilitate ferroptosis resistance in glioblastoma.
Wang Z et al.·Cancer Lett
2024
KLF5-regulated ZDHHC8 reduces chemosensitivity in high-grade serous ovarian cancer through β-catenin signaling.
Xue Z et al.·Sci Rep
2025
Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome.
Nunes N et al.·Genet Res (Camb)
2024Cohort
Identification of Ten-Gene Related to Lipid Metabolism for Predicting Overall Survival of Breast Invasive Carcinoma.
Wang Z et al.·Contrast Media Mol Imaging
2022
No association was found between a functional SNP in ZDHHC8 and schizophrenia in a Japanese case-control population.
Saito S et al.·Neurosci Lett
2005Clinical trial
Mitochondrial Citrate Transporter-dependent Metabolic Signature in the 22q11.2 Deletion Syndrome.
Napoli E et al.·J Biol Chem
2015
Palmitoylation of cdc42 Promotes Spine Stabilization and Rescues Spine Density Deficit in a Mouse Model of 22q11.2 Deletion Syndrome.
Moutin E et al.·Cereb Cortex
2017Functional
No association between the putative functional ZDHHC8 single nucleotide polymorphism rs175174 and schizophrenia in large European samples.
Glaser B et al.·Biol Psychiatry
2005Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools