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ZDHHC4

gene
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Also known as FLJ10479ZNF374

Summary

ZDHHC4 (zDHHC palmitoyltransferase 4, HGNC:18471) is a protein-coding gene on chromosome 7p22.1, encoding Palmitoyltransferase ZDHHC4 (Q9NPG8). Palmitoyltransferase that catalyzes the addition of palmitate onto protein substrates including the D(2) dopamine receptor DRD2, GSK3B or MAVS.

Enables palmitoyltransferase activity. Involved in positive regulation of innate immune response and protein localization to plasma membrane. Located in Golgi apparatus and endoplasmic reticulum.

Source: NCBI Gene 55146 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 70 total
  • MANE Select transcript: NM_001134389

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:18471
Approved symbolZDHHC4
NamezDHHC palmitoyltransferase 4
Location7p22.1
Locus typegene with protein product
StatusApproved
AliasesFLJ10479, ZNF374
Ensembl geneENSG00000136247
Ensembl biotypeprotein_coding
Entrez55146

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 40 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000335965, ENST00000396706, ENST00000396707, ENST00000396709, ENST00000396713, ENST00000405731, ENST00000474097, ENST00000474738, ENST00000483589, ENST00000489138, ENST00000493944, ENST00000496017, ENST00000870384, ENST00000870385, ENST00000870386, ENST00000870387, ENST00000870388, ENST00000870389, ENST00000870390, ENST00000870391, ENST00000870392, ENST00000870393, ENST00000870394, ENST00000870395, ENST00000870396, ENST00000870397, ENST00000870398, ENST00000870399, ENST00000870400, ENST00000870401, ENST00000870402, ENST00000937701, ENST00000937702, ENST00000937703, ENST00000937704, ENST00000937705, ENST00000937706, ENST00000965763, ENST00000965764, ENST00000965765, ENST00000965766, ENST00000965767, ENST00000965768, ENST00000965769, ENST00000965770

RefSeq mRNA: 12 — MANE Select: NM_001134389 NM_001134387, NM_001134388, NM_001134389, NM_001371292, NM_001371293, NM_001371294, NM_001371295, NM_001371296, NM_001371297, NM_001371298, NM_001371299, NM_018106

CCDS: CCDS5352

Canonical transcript exons

ENST00000335965 — 8 exons

ExonStartEnd
ENSE0000092387965850166585260
ENSE0000152603265785666578720
ENSE0000155741365886176589374
ENSE0000195254065774546577498
ENSE0000352056865805556580678
ENSE0000354826665820736582251
ENSE0000365357365816076581680
ENSE0000378477765833066583431

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5802 / max 132.6821, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
7715425.25951815
771551.3207930

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
left testisUBERON:000453395.57gold quality
right testisUBERON:000453495.45gold quality
islet of LangerhansUBERON:000000695.43gold quality
body of pancreasUBERON:000115095.20gold quality
stromal cell of endometriumCL:000225595.05gold quality
muscle layer of sigmoid colonUBERON:003580594.69gold quality
mucosa of stomachUBERON:000119994.64gold quality
gastrocnemiusUBERON:000138894.34gold quality
body of stomachUBERON:000116194.13gold quality
lower esophagus muscularis layerUBERON:003583394.04gold quality
lower esophagusUBERON:001347394.01gold quality
right adrenal gland cortexUBERON:003582794.00gold quality
right adrenal glandUBERON:000123393.98gold quality
muscle of legUBERON:000138393.98gold quality
left lobe of thyroid glandUBERON:000112093.92gold quality
right lobe of thyroid glandUBERON:000111993.90gold quality
esophagogastric junction muscularis propriaUBERON:003584193.89gold quality
olfactory segment of nasal mucosaUBERON:000538693.88gold quality
hindlimb stylopod muscleUBERON:000425293.86gold quality
right uterine tubeUBERON:000130293.83gold quality
left adrenal glandUBERON:000123493.80gold quality
left adrenal gland cortexUBERON:003582593.69gold quality
gall bladderUBERON:000211093.62gold quality
thoracic aortaUBERON:000151593.34gold quality
popliteal arteryUBERON:000225093.34gold quality
tibial arteryUBERON:000761093.33gold quality
pancreasUBERON:000126493.31gold quality
testisUBERON:000047393.30gold quality
ascending aortaUBERON:000149693.30gold quality
left coronary arteryUBERON:000162693.29gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes10.02

Regulation

Is transcription factor: no

Cross-species orthologs

12 orthologs

OrganismSymbolGene ID
danio_reriozdhhc4ENSDARG00000045159
mus_musculusZdhhc4ENSMUSG00000001844
rattus_norvegicusZdhhc4ENSRNOG00000051699
drosophila_melanogasterDnz1FBGN0027453
drosophila_melanogasterCG1407FBGN0033474
drosophila_melanogasterCG17287FBGN0034202
caenorhabditis_elegansdhhc-7WBGENE00007637
caenorhabditis_elegansdhhc-12WBGENE00010323
caenorhabditis_elegansdhhc-2WBGENE00012948
caenorhabditis_elegansWBGENE00014075
caenorhabditis_elegansWBGENE00016620
caenorhabditis_elegansWBGENE00020066

Paralogs (17): ZDHHC6 (ENSG00000023041), ZDHHC15 (ENSG00000102383), ZDHHC2 (ENSG00000104219), ZDHHC7 (ENSG00000153786), ZDHHC1 (ENSG00000159714), ZDHHC12 (ENSG00000160446), ZDHHC3 (ENSG00000163812), ZDHHC19 (ENSG00000163958), ZDHHC14 (ENSG00000175048), ZDHHC21 (ENSG00000175893), ZDHHC22 (ENSG00000177108), ZDHHC20 (ENSG00000180776), ZDHHC23 (ENSG00000184307), ZDHHC9 (ENSG00000188706), ZDHHC11 (ENSG00000188818), ZDHHC18 (ENSG00000204160), ZDHHC11B (ENSG00000206077)

Protein

Protein identifiers

Palmitoyltransferase ZDHHC4 — Q9NPG8 (reviewed: Q9NPG8)

Alternative names: Zinc finger DHHC domain-containing protein 4, Zinc finger protein 374

All UniProt accessions (2): C9J5I9, Q9NPG8

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that catalyzes the addition of palmitate onto protein substrates including the D(2) dopamine receptor DRD2, GSK3B or MAVS. Mediates GSK3B palmitoylation to prevent its AKT1-mediated phosphorylation leading to activation of the STAT3 signaling pathway. Also catalyzes MAVS palmitoylation which promotes its stabilization and activation by inhibiting ‘Lys-48’- but facilitating ‘Lys-63’-linked ubiquitination.

Subunit / interactions. Interacts with CPT1A.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell membrane.

Domain organisation. The C-terminal di-lysine motif confers endoplasmic reticulum localization. The DHHC domain is required for palmitoyltransferase activity.

Similarity. Belongs to the DHHC palmitoyltransferase family.

RefSeq proteins (12): NP_001127859, NP_001127860, NP_001127861, NP_001358221, NP_001358222, NP_001358223, NP_001358224, NP_001358225, NP_001358226, NP_001358227, NP_001358228, NP_060576 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001594Palmitoyltrfase_DHHCDomain
IPR039859PFA4/ZDH16/20/ERF2-likeFamily

Pfam: PF01529

Enzyme classification (BRENDA):

  • EC 2.3.1.225 — protein S-acyltransferase (BRENDA: 9 organisms, 108 substrates, 15 inhibitors, 6 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
PALMITOYL-COA0.0052–0.00592
[N-MYRISTOYLATED GLY-CYS-GLY TRIPEPTIDE]-L-CYSTE0.0008–0.00132

Catalyzed reactions (Rhea), 1 shown:

  • L-cysteinyl-[protein] + hexadecanoyl-CoA = S-hexadecanoyl-L-cysteinyl-[protein] + CoA (RHEA:36683)

UniProt features (25 total): topological domain 6, transmembrane region 5, mutagenesis site 4, sequence conflict 4, sequence variant 2, chain 1, domain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9NPG8-F183.990.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 179 (s-palmitoyl cysteine intermediate)

Mutagenesis-validated functional residues (4):

PositionPhenotype
179complete loss of palmitoyltransferase activity.
340does not affect localization to the endoplasmic reticulum.
341does not affect localization to the endoplasmic reticulum.
342impaired localization to the endoplasmic reticulum.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PROTEIN_TARGETING, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, chr7p22, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, DOUGLAS_BMI1_TARGETS_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (7): protein targeting to membrane (GO:0006612), positive regulation of innate immune response (GO:0045089), protein localization to plasma membrane (GO:0072659), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), positive regulation of cell migration (GO:0030335), negative regulation of cell migration (GO:0030336), cellular response to diacyl bacterial lipopeptide (GO:0071726)

GO Molecular Function (5): palmitoyltransferase activity (GO:0016409), protein-cysteine S-palmitoyltransferase activity (GO:0019706), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (6): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cell migration2
regulation of cell migration2
cytoplasm2
endomembrane system2
intracellular membrane-bounded organelle2
protein targeting1
establishment of protein localization to membrane1
positive regulation of response to biotic stimulus1
positive regulation of defense response1
positive regulation of response to external stimulus1
innate immune response1
regulation of innate immune response1
positive regulation of immune response1
protein localization to membrane1
protein localization to cell periphery1
positive regulation of cytokine production1
pattern recognition receptor signaling pathway1
intracellular receptor signaling pathway1
positive regulation of cell motility1
negative regulation of cell motility1
cellular response to bacterial lipopeptide1
response to diacyl bacterial lipopeptide1
acyltransferase activity, transferring groups other than amino-acyl groups1
palmitoyltransferase activity1
protein-cysteine S-acyltransferase activity1
binding1
catalytic activity1
transferase activity1
Golgi apparatus1
bounding membrane of organelle1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
membrane1
cell periphery1
cellular anatomical structure1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ZDHHC4AWAT2Q6E213802
ZDHHC4ZDHHC22Q8N966690
ZDHHC4PPT2Q9UMR5527
ZDHHC4ZDHHC6Q9H6R6505
ZDHHC4ZDHHC13Q8IUH4474
ZDHHC4INTS15Q96N11471
ZDHHC4PPT1P50897471
ZDHHC4LYPLA1O75608459
ZDHHC4ZDHHC17Q8IUH5453
ZDHHC4ABHD17AQ96GS6441
ZDHHC4MSANTD4Q8NCY6432
ZDHHC4IL2P01585428
ZDHHC4ZDHHC24Q6UX98406
ZDHHC4ZDHHC8Q9ULC8399
ZDHHC4LYPLA2O95372394

IntAct

12 interactions, top by confidence:

ABTypeScore
CLDND1ZDHHC4psi-mi:“MI:0915”(physical association)0.560
TUSC5ZDHHC4psi-mi:“MI:0915”(physical association)0.560
ZDHHC4CLDND1psi-mi:“MI:0915”(physical association)0.560
ZDHHC4DRD2psi-mi:“MI:0915”(physical association)0.370
ZDHHC4psi-mi:“MI:0915”(physical association)0.370
ZDHHC4MAVSpsi-mi:“MI:0914”(association)0.350
SLC44A2CLGNpsi-mi:“MI:0914”(association)0.350
SLC44A5UPK3BL1psi-mi:“MI:0914”(association)0.350
TUSC5ZDHHC4psi-mi:“MI:0915”(physical association)0.000

BioGRID (11): ZDHHC4 (Synthetic Lethality), ZDHHC4 (Two-hybrid), TUSC5 (Two-hybrid), ZDHHC4 (Two-hybrid), MAVS (Affinity Capture-MS), UBQLN1 (Affinity Capture-MS), ZFAND2B (Affinity Capture-MS), ZDHHC4 (Affinity Capture-MS), ZDHHC4 (Affinity Capture-MS), ZDHHC4 (Affinity Capture-RNA), ZDHHC4 (Proximity Label-MS)

ESM2 similar proteins: A0A087WTH1, A0A125YWU9, A0PK84, A6PVL3, C9JQL5, F1QHM7, F1QX91, O15503, O41933, O70418, O88728, P0DI73, P13164, P26376, Q01628, Q01629, Q08755, Q0II74, Q21642, Q32L65, Q3UNB8, Q3YBM2, Q5FVR1, Q5FWL7, Q5I0I2, Q5R8D6, Q5RF75, Q5Y5T3, Q6DHI1, Q76IC6, Q7M734, Q7TQJ1, Q8BGI3, Q8CES1, Q8CFA6, Q8IYP9, Q8N6L7, Q8WVZ1, Q91WU6, Q921C1

Diamond homologs: A0A0R4IDP3, A2CEX1, A2VEY9, A5WVX9, B3DN87, C8VCL4, E1BLT8, E7F021, E7F587, E7FBS9, E7FH11, E9PTT0, E9QCD3, F1Q7H8, F1QAM1, F1QHM7, F1QX91, F1QXD3, F1R013, F1RE57, J9VJ99, O60069, O74384, O80685, P42836, P59267, P59268, Q04629, Q0VC89, Q10L01, Q2TGJ1, Q2TGJ4, Q2TGK3, Q2THW7, Q2THW8, Q2THW9, Q2THX0, Q2THX1, Q4R690, Q4WZL8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

70 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance45
Likely benign10
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1217 predictions. Top by Δscore:

VariantEffectΔscore
7:6577496:GCG:Gdonor_gain1.0000
7:6577718:G:GTdonor_gain1.0000
7:6578716:GAAAT:Gdonor_gain1.0000
7:6578721:G:GGdonor_gain1.0000
7:6580551:GTA:Gacceptor_loss1.0000
7:6580553:A:AGacceptor_gain1.0000
7:6580554:G:GGacceptor_gain1.0000
7:6580554:GCT:Gacceptor_gain1.0000
7:6580554:GCTGC:Gacceptor_gain1.0000
7:6581602:TTCA:Tacceptor_loss1.0000
7:6581603:TCA:Tacceptor_loss1.0000
7:6581604:CAG:Cacceptor_loss1.0000
7:6581605:A:AGacceptor_gain1.0000
7:6581605:A:Tacceptor_loss1.0000
7:6581606:G:GGacceptor_gain1.0000
7:6581606:GAT:Gacceptor_gain1.0000
7:6581676:ACGAG:Adonor_loss1.0000
7:6581677:CGAGG:Cdonor_loss1.0000
7:6581678:GAGG:Gdonor_loss1.0000
7:6581679:AGGTA:Adonor_loss1.0000
7:6581682:T:Gdonor_loss1.0000
7:6583432:G:GGdonor_gain1.0000
7:6585010:GTGCA:Gacceptor_loss1.0000
7:6585011:TGCA:Tacceptor_loss1.0000
7:6585012:GCAG:Gacceptor_loss1.0000
7:6585013:CAGG:Cacceptor_loss1.0000
7:6585015:G:Tacceptor_loss1.0000
7:6585015:GGT:Gacceptor_gain1.0000
7:6585015:GGTGT:Gacceptor_gain1.0000
7:6585258:CAGG:Cdonor_loss1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000276579 (7:6577588 A>G), RS1000351181 (7:6587267 GT>G,GTT), RS1000461208 (7:6582306 A>C,G), RS1000619936 (7:6583011 C>G), RS1000630803 (7:6588172 C>T), RS1000658504 (7:6588393 C>T), RS1000775252 (7:6577388 C>A), RS1000814624 (7:6582725 C>T), RS1001436653 (7:6580181 A>G), RS1001693729 (7:6584158 T>C), RS1001894089 (7:6581816 C>A,G,T), RS1002011440 (7:6577047 G>A), RS1002229185 (7:6577982 A>T), RS1002303541 (7:6586950 T>G), RS1002333160 (7:6587203 G>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

StudyTraitp-value
GCST005951_155Body mass index1.000000e-08

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004340body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arsenitedecreases expression, increases abundance2
aristolochic acid Iincreases expression1
FR900359increases phosphorylation1
terbufosdecreases methylation1
di-n-butylphosphoric acidaffects expression1
jinfukangaffects cotreatment, increases expression1
Temozolomideincreases expression1
Sunitinibincreases expression1
Arsenicdecreases expression, increases abundance1
Cisplatinaffects cotreatment, increases expression1
Fonofosdecreases methylation1
Parathiondecreases methylation1
Smokedecreases expression1
Valproic Acidaffects expression1
Cyclosporineincreases expression1
Copper Sulfatedecreases expression1
tert-Butylhydroperoxidedecreases expression1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_TY96HAP1 ZDHHC4 (-) 1Cancer cell lineMale
CVCL_TY97HAP1 ZDHHC4 (-) 2Cancer cell lineMale
CVCL_TY98HAP1 ZDHHC4 (-) 3Cancer cell lineMale
CVCL_TY99HAP1 ZDHHC4 (-) 4Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot