ZDHHC14

Chr 6

zDHHC palmitoyltransferase 14

Also known as: NEW1CP

ZDHHC14 encodes a palmitoyltransferase that catalyzes the addition of palmitate to protein substrates including the beta-2 adrenergic receptor, thereby regulating G protein-coupled receptor signaling from the endoplasmic reticulum. Mutations cause autosomal recessive intellectual disability with dysmorphic features and behavioral abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.42), suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.42
Clinical SummaryZDHHC14
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.715
Z-score 3.51
OE 0.18 (0.090.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.24Z-score
OE missense 0.64 (0.570.72)
192 obs / 301.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.18 (0.090.42)
00.351.4
Missense OE0.64 (0.570.72)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 4 / 21.6Missense obs/exp: 192 / 301.2Syn Z: 0.06
DN
0.6356th %ile
GOF
0.6638th %ile
LOF
0.53top 25%

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZDHHC14 · 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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