ZDHHC21

Chr 9

zDHHC palmitoyltransferase 21

Also known as: DHHC-21, DHHC21, DNZ1, HSPC097

NCBI Gene: 340481ENSG00000175893UniProt: Q8IVQ6OMIM: 614605

This palmitoyltransferase catalyzes the addition of palmitate groups to various protein substrates, including sex steroid hormone receptors, FYN kinase, and other signaling proteins, thereby regulating their membrane localization and signaling functions. The gene is not currently associated with any known Mendelian disease or well-defined clinical phenotype. The gene appears tolerant to loss-of-function variants based on population genetics data.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.74
Clinical Summary— ZDHHC21
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
114 unique Pathogenic / Likely Pathogenic· 35 VUS of 173 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.028
Z-score 2.26
OE 0.35 (0.18–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.32Z-score
OE missense 0.92 (0.80–1.07)
131 obs / 141.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.18–0.74)
0≤0.351.4
Missense OE0.92 (0.80–1.07)
0≤0.61.4
Synonymous OE1.70
0≤1.21.6
LoF obs/exp: 5 / 14.2Missense obs/exp: 131 / 141.8Syn Z: -3.68
DN
0.6842th %ile
GOF
0.78top 25%
LOF
0.2483th %ile

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.

GOFprediction above median
DNprediction above median

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

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic107
Likely Pathogenic7
VUS35
107
Pathogenic
7
Likely Pathogenic
35
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
107
0
107
Likely Pathogenic
0
0
7
0
7
VUS
0
29
6
0
35
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0291200149

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZDHHC21 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients