ZDHHC7

Chr 16

zDHHC palmitoyltransferase 7

Also known as: DHHC7, SERZ-B, SERZ1, ZNF370

NCBI Gene: 55625 ENSG00000153786 OMIM: 614604

This protein is a Golgi-localized palmitoyltransferase that catalyzes the addition of palmitate to various protein substrates, regulating their membrane localization and function in processes including steroid hormone signaling, G protein-coupled receptor pathways, and cell polarity. Mutations in ZDHHC7 cause autosomal recessive intellectual disability with seizures and hypotonia. The gene shows tolerance to loss-of-function variants (pLI 0.001, LOEUF 0.788), consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein-cysteine S-palmitoyltransferase activity. Involved in several processes, including nuclear receptor-mediated steroid hormone signaling pathway; regulation of protein localization; and regulation of signal transduction. Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.79

Clinical Summary— ZDHHC7

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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

54 VUS of 64 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?

0.79LOEUF

pLI 0.001

Z-score 2.24

OE 0.44 (0.26–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.60Z-score

OE missense 0.89 (0.79–1.00)

191 obs / 215.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.26–0.79)

0≤0.351.4

Missense OE?0.89 (0.79–1.00)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 8 / 18.3Missense obs/exp: 191 / 215.7Syn Z: -1.32

This gene — mechanism propensity

0.6647th %ile

GOF

0.6932th %ile

LOF

0.3453th %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

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign1

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	54	54
Likely Benign	1	1
Benign	0	0
Total	55	55

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap ZDHHC7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →