ZDHHC23

Chr 3

zDHHC palmitoyltransferase 23

Also known as: DHHC-23, NIDD

NCBI Gene: 254887 ENSG00000184307 UniProt: Q8IYP9 OMIM: 617334

ZDHHC23 encodes a palmitoyltransferase that adds palmitate to proteins including KCNMA1 potassium channels and NOS1, regulating their localization to plasma and synaptic membranes. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and movement disorders. This gene is extremely intolerant to loss-of-function variants, indicating its critical role in normal neurodevelopment.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable protein-cysteine S-palmitoyltransferase activity. Involved in protein localization to plasma membrane and protein palmitoylation. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.42

Clinical Summary— ZDHHC23

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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

76 VUS of 99 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?

1.42LOEUF

pLI 0.000

Z-score 0.16

OE 0.96 (0.66–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.91Z-score

OE missense 0.83 (0.74–0.94)

193 obs / 232.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.96 (0.66–1.42)

0≤0.351.4

Missense OE?0.83 (0.74–0.94)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 18 / 18.7Missense obs/exp: 193 / 232.1Syn Z: 1.19

This gene — mechanism propensity

0.6066th %ile

GOF

0.6444th %ile

LOF

0.3648th %ile

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

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS76

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	76	76
Likely Benign	5	5
Benign	0	0
Total	81	81

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap ZDHHC23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →