ZDHHC23

Chr 3

zDHHC palmitoyltransferase 23

Also known as: DHHC-23, NIDD

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.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.42
Clinical SummaryZDHHC23
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.42LOEUF
pLI 0.000
Z-score 0.16
OE 0.96 (0.661.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.91Z-score
OE missense 0.83 (0.740.94)
193 obs / 232.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.96 (0.661.42)
00.351.4
Missense OE0.83 (0.740.94)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 18 / 18.7Missense obs/exp: 193 / 232.1Syn Z: 1.19
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZDHHC23 · 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

No active trials found for this gene.

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Clinical Literature
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