ZDHHC9

Chr XX-linked

zDHHC palmitoyltransferase 9

Also known as: CGI89, CXorf11, DHHC9, MMSA1, MRXSR, MRXSZ, ZDHHC10, ZNF379

NCBI Gene: 51114ENSG00000188706UniProt: Q9Y397

This gene encodes an integral membrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein forms a complex with golgin subfamily A member 7 and functions as a palmitoyltransferase. This protein specifically palmitoylates HRAS and NRAS. Mutations in this gene are associated with X-linked cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic, Raymond typeMIM #300799
X-linked
0
Active trials
131
Pathogenic / LP
412
ClinVar variants
21
Pubs (1 yr)
2.6
Missense Z
0.48
LOEUF
Clinical Summary— ZDHHC9
🧬
Gene-Disease Validity (ClinGen)
syndromic X-linked intellectual disability Raymond type · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
131 Pathogenic / Likely Pathogenic· 125 VUS of 412 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.737
Z-score 2.85
OE 0.15 (0.06–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.55Z-score
OE missense 0.42 (0.35–0.52)
66 obs / 155.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.06–0.48)
0≤0.351.4
Missense OE0.42 (0.35–0.52)
0≤0.61.4
Synonymous OE1.20
0≤1.21.6
LoF obs/exp: 2 / 13.1Missense obs/exp: 66 / 155.5Syn Z: -1.17
GOF
DN
0.5378th %ile
GOF
0.6542th %ile
LOF
0.50top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

412 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
Likely Pathogenic15
VUS125
Likely Benign107
Benign40
Conflicting9
116
Pathogenic
15
Likely Pathogenic
125
VUS
107
Likely Benign
40
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
113
0
116
Likely Pathogenic
5
2
8
0
15
VUS
2
104
17
2
125
Likely Benign
0
7
38
62
107
Benign
0
2
30
8
40
Conflicting
—9
Total1011520672412

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

View in ClinVar →

ZDHHC9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ZDHHC9-related syndromic intellectual developmental disorder

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Targeting the ZDHHC9-mediated STAT1 palmitoylation-phosphorylation conversion inhibits gastric cancer progression.
Bai X et al.·J Gastroenterol
2026
ASF1B promotes gastric cancer liver metastasis through inhibiting ZDHHC9/PCBP1/ SLC7A11 signaling axis mediated ferroptosis.
Wang M et al.·NPJ Precis Oncol
2026Open Access
Expanding the spectrum of AFF2 undifferentiated sarcoma associated to endometriosis: a novel ZDHHC9::AFF2 fusion sarcoma with high-grade features and poor prognosis.
Arciuolo D et al.·Pathologica
2025Open Access
Micro-scale control of oligodendrocyte morphology and myelination by the intellectual disability-linked protein acyltransferase ZDHHC9.
Jeong HK et al.·Elife
2025Open Access
Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer.
Zhou D et al.·Front Immunol
2025Open Access
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