ZDHHC11

Chr 5

zDHHC palmitoyltransferase 11

Also known as: ZNF399

NCBI Gene: 79844 ENSG00000188818 UniProt: Q9H8X9

The ZDHHC11 protein is an endoplasmic reticulum-localized palmitoyltransferase that catalyzes the addition of palmitate onto protein substrates, regulating their membrane association and cellular localization. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene shows extremely high constraint against loss-of-function variants, indicating it is essential for normal human development.

ResearchSummary from RefSeq, UniProt

Enables signaling adaptor activity. Involved in antiviral innate immune response and positive regulation of defense response to virus by host. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.54

Clinical Summary— ZDHHC11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

100 VUS of 140 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.000

Z-score -0.34

OE 1.08 (0.77–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.92Z-score

OE missense 1.17 (1.06–1.30)

259 obs / 220.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.08 (0.77–1.54)

0≤0.351.4

Missense OE?1.17 (1.06–1.30)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 22 / 20.4Missense obs/exp: 259 / 220.6Syn Z: -2.22

This gene — mechanism propensity

0.6550th %ile

GOF

0.80top 10%

LOF

0.2969th %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

140 submitted variants in ClinVar

ClinVar

Classification Summary

VUS100

Likely Benign19

Benign1

100

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	100	0	0	100
Likely Benign	13	3	3	19
Benign	1	0	0	1
Total	114	3	3	120

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

View in ClinVar →

136 pathogenic / likely-pathogenic (of 177) ClinVar copy-number / structural variants overlap ZDHHC11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →