ZDHHC5

Summary

ZDHHC5 (zDHHC palmitoyltransferase 5, HGNC:18472) is a protein-coding gene on chromosome 11q12.1, encoding Palmitoyltransferase ZDHHC5 (Q9C0B5). Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sen….

Enables protein-cysteine S-palmitoyltransferase activity. Involved in positive regulation of defense response; positive regulation of protein localization to plasma membrane; and protein localization to plasma membrane. Acts upstream of or within protein palmitoylation. Located in nucleoplasm; phagocytic vesicle; and plasma membrane.

Source: NCBI Gene 25921 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (Limited, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 120 total
• MANE Select transcript: NM_015457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18472
Approved symbol	ZDHHC5
Name	zDHHC palmitoyltransferase 5
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1748, ZNF375, DHHC5
Ensembl gene	ENSG00000156599
Ensembl biotype	protein_coding
OMIM	614586
Entrez	25921

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000287169, ENST00000524540, ENST00000527090, ENST00000527985, ENST00000528177, ENST00000529447, ENST00000529480, ENST00000532842, ENST00000858132, ENST00000858133, ENST00000924859, ENST00000924860, ENST00000924861, ENST00000924862, ENST00000924863, ENST00000954577, ENST00000954578, ENST00000954579, ENST00000954580, ENST00000954581

RefSeq mRNA: 1 — MANE Select: NM_015457 NM_015457

CCDS: CCDS7965

Canonical transcript exons

ENST00000287169 — 12 exons

Exon	Start	End
ENSE00001027369	57672021	57673194
ENSE00001027373	57690335	57690437
ENSE00001027380	57668114	57668187
ENSE00001027383	57690031	57690203
ENSE00001027388	57699866	57701182
ENSE00003463967	57692611	57692702
ENSE00003527661	57696761	57696873
ENSE00003556352	57695920	57696043
ENSE00003569944	57688508	57688665
ENSE00003575717	57693783	57693915
ENSE00003595086	57682422	57682543
ENSE00003649195	57698559	57699418

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.9628 / max 193.3725, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114317	32.1523	1821
114316	2.7848	1426
114319	0.0139	5
114318	0.0118	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	97.77	gold quality
gingival epithelium	UBERON:0001949	97.49	gold quality
ileal mucosa	UBERON:0000331	97.27	gold quality
upper arm skin	UBERON:0004263	97.22	gold quality
gingiva	UBERON:0001828	97.12	gold quality
secondary oocyte	CL:0000655	96.90	gold quality
tibialis anterior	UBERON:0001385	96.47	silver quality
stromal cell of endometrium	CL:0002255	95.94	gold quality
pharyngeal mucosa	UBERON:0000355	95.76	gold quality
parotid gland	UBERON:0001831	95.60	gold quality
nasal cavity epithelium	UBERON:0005384	95.48	gold quality
lower esophagus mucosa	UBERON:0035834	95.40	gold quality
esophagus mucosa	UBERON:0002469	95.26	gold quality
mammalian vulva	UBERON:0000997	95.12	gold quality
penis	UBERON:0000989	95.07	gold quality
tibia	UBERON:0000979	95.04	gold quality
oral cavity	UBERON:0000167	94.65	gold quality
nipple	UBERON:0002030	94.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.47	gold quality
upper leg skin	UBERON:0004262	94.39	gold quality
palpebral conjunctiva	UBERON:0001812	94.34	gold quality
islet of Langerhans	UBERON:0000006	93.78	gold quality
epithelial cell of pancreas	CL:0000083	93.58	gold quality
tonsil	UBERON:0002372	93.56	gold quality
left ventricle myocardium	UBERON:0006566	93.55	gold quality
epithelium of nasopharynx	UBERON:0001951	93.40	gold quality
deltoid	UBERON:0001476	93.38	gold quality
zone of skin	UBERON:0000014	93.24	gold quality
tongue	UBERON:0001723	93.23	gold quality
body of tongue	UBERON:0011876	93.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

101 targeting ZDHHC5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-7845-5P	99.88	64.88	771

Literature-anchored findings (GeneRIF, showing 16)

• Data show that palmitoyl acyltransferases DHHC5, DHHC6, and DHHC8 appear to be S-acylated on three cysteine residues within a novel CCX(7-13)C(S/T) motif downstream of a conserved Asp-His-His-Cys cysteine-rich domain. (PMID:19801377)
• ZDHHC5 and SSTR5 are colocalized at the plasma membrane and coexpression of ZDHHC5 increased palmitoylation of SSTR5 whereas knock-down of endogenous ZDHHC5 by siRNAs decreased it. (PMID:21820437)
• Data indicate that DHHC5 has oncogenic capacity and contributes to tumor formation in non-small cell lung cancer. (PMID:25573953)
• We demonstrated that LXR stimulation decreases mRNA and protein expression of FLOT2 and DHHC5 in MCF-7 cells. LXR stimulation also reduces Akt phosphorylation and its localization at the plasma membrane (PMID:28739689)
• High ZDHHC5 expression is associated with Glioma. (PMID:28775165)
• DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. (PMID:30605677)
• This work uncovers a novel mechanism of DHHC5 regulation by Golga7b and demonstrates a role for the DHHC5/Golga7b complex in the regulation of cell adhesion. (PMID:31402609)
• DHHC5 Mediates beta-Adrenergic Signaling in Cardiomyocytes by Targeting Galpha Proteins. (PMID:31547976)
• ZDHHC5-mediated S-palmitoylation is indispensable for NOD1/2 recruitment to bacteria containing phagosomes. (PMID:31649195)
• Study findings identified six miRNAs related to gastric adenocarcinoma prognosis and suggested that downregulated miR-96-5p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells. (PMID:31885423)
• Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase. (PMID:32737405)
• Regulation and function of the palmitoyl-acyltransferase ZDHHC5. (PMID:33415776)
• The interactions of ZDHHC5/GOLGA7 with SARS-CoV-2 spike (S) protein and their effects on S protein’s subcellular localization, palmitoylation and pseudovirus entry. (PMID:34961524)
• ZDHHC5-mediated NLRP3 palmitoylation promotes NLRP3-NEK7 interaction and inflammasome activation. (PMID:38092000)
• Reduction of DHHC5-mediated beclin 1 S-palmitoylation underlies autophagy decline in aging. (PMID:38177673)
• ZDHHC5-mediated S-palmitoylation of FAK promotes its membrane localization and epithelial-mesenchymal transition in glioma. (PMID:38233791)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zdhhc5a	ENSDARG00000016263
danio_rerio	zdhhc5b	ENSDARG00000087417
mus_musculus	Zdhhc5	ENSMUSG00000034075
rattus_norvegicus	Zdhhc5	ENSRNOG00000006832

Paralogs (1): ZDHHC8 (ENSG00000099904)

Protein

Protein identifiers

Palmitoyltransferase ZDHHC5 — Q9C0B5 (reviewed: Q9C0B5)

Alternative names: Zinc finger DHHC domain-containing protein 5, Zinc finger protein 375

All UniProt accessions (4): Q9C0B5, E9PJ97, E9PMA5, H0YEF4

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sensing or cardiac functions. Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins. Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2. Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2. Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes. Also participates in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane. Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis. Controls oligodendrocyte development by catalyzing STAT3 palmitoylation. Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD. Palmitoylates NLRP3 to promote inflammasome assembly and activation. Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD.

Subcellular location. Cell membrane. Synapse.

Post-translational modifications. Phosphorylation regulates association with endocytic proteins and its subcellular localization. Phosphorylation by LYN during fatty acid uptake leads to inactivation of the activity. Autopalmitoylated. Palmitoylation of the C-terminal tail regulates stimulation-dependent plasma membrane motility.

Domain organisation. The DHHC domain is required for palmitoyltransferase activity.

Similarity. Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0B5-1	1	yes
Q9C0B5-2	2

RefSeq proteins (1): NP_056272* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001594	Palmitoyltrfase_DHHC	Domain

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.

Substrate	Km (mM)	Measurements
PALMITOYL-COA	0.0052–0.0059	2
[N-MYRISTOYLATED GLY-CYS-GLY TRIPEPTIDE]-L-CYSTE	0.0008–0.0013	2

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (49 total): modified residue 28, topological domain 5, compositionally biased region 4, transmembrane region 4, mutagenesis site 2, chain 1, domain 1, region of interest 1, active site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0B5-F1	59.32	0.27

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): 134 (s-palmitoyl cysteine intermediate)

Post-translational modifications (28): 91, 247, 294, 296, 299, 303, 345, 348, 350, 380, 398, 406, 409, 411, 415, 425, 429, 432, 436, 529 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
91	more than 50% loss of activity.
533	more than 50% loss of fyn-mediated phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9694548	Maturation of spike protein

MSigDB gene sets: 247 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, AAGCAAT_MIR137, GGTGTGT_MIR329, PAX4_01, GOBP_INFLAMMATORY_RESPONSE, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, TATTATA_MIR374, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY

GO Biological Process (22): lipid transport (GO:0006869), protein palmitoylation (GO:0018345), innate immune response (GO:0045087), protein maturation (GO:0051604), positive regulation of pattern recognition receptor signaling pathway (GO:0062208), protein localization to plasma membrane (GO:0072659), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), positive regulation of pyroptotic inflammatory response (GO:0140639), non-canonical inflammasome complex assembly (GO:0160075), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), positive regulation of protein localization to plasma membrane (GO:1903078), positive regulation of protein localization to phagocytic vesicle (GO:1905171), immune system process (GO:0002376), fatty acid transport (GO:0015908), protein catabolic process (GO:0030163), response to muramyl dipeptide (GO:0032495), defense response to bacterium (GO:0042742), NLRP3 inflammasome complex assembly (GO:0044546), nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427), nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431), protein K63-linked ubiquitination (GO:0070534), pyroptotic cell death (GO:0141201)

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 (12): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), phagocytic vesicle (GO:0045335), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), postsynaptic specialization, intracellular component (GO:0099091), endomembrane system (GO:0012505), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Translation of Structural Proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	3
protein metabolic process	2
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	2
transport	1
lipid localization	1
protein lipidation	1
protein acylation	1
immune response	1
defense response to symbiont	1
gene expression	1
pattern recognition receptor signaling pathway	1
positive regulation of signal transduction	1
positive regulation of innate immune response	1
regulation of pattern recognition receptor signaling pathway	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of biological quality	1
positive regulation of inflammatory response	1
pyroptotic inflammatory response	1
protein-containing complex assembly	1
positive regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
positive regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
positive regulation of protein localization	1
protein localization to phagocytic vesicle	1
regulation of protein localization to phagocytic vesicle	1
biological_process	1
lipid transport	1
monocarboxylic acid transport	1
macromolecule catabolic process	1
response to nitrogen compound	1
response to oxygen-containing compound	1
defense response	1
response to bacterium	1

Protein interactions and networks

STRING

2292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC5	GOLGA7	Q7Z5G4	917
ZDHHC5	FXYD1	O00168	694
ZDHHC5	GOLGA7B	Q2TAP0	602
ZDHHC5	DLG4	P78352	591
ZDHHC5	ZDHHC22	Q8N966	580
ZDHHC5	GRIP2	Q9C0E4	576
ZDHHC5	FLOT2	Q14254	548
ZDHHC5	ZDHHC16	Q969W1	545
ZDHHC5	PPT1	P50897	543
ZDHHC5	ABHD17A	Q96GS6	524
ZDHHC5	LYPLA1	O75608	493
ZDHHC5	GRIP1	Q9Y3R0	487
ZDHHC5	CTNND2	Q9UQB3	482
ZDHHC5	PPT2	Q9UMR5	460
ZDHHC5	LYPLA2	O95372	458

IntAct

83 interactions, top by confidence:

A	B	Type	Score
ZDHHC5	S	psi-mi:“MI:0914”(association)	0.860
ZDHHC5	S	psi-mi:“MI:0915”(physical association)	0.860
S	ZDHHC5	psi-mi:“MI:0915”(physical association)	0.860
S	ZDHHC5	psi-mi:“MI:0403”(colocalization)	0.860
S	GOLGA7	psi-mi:“MI:0914”(association)	0.820
GOLGA7	S	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GOLGA7	ZDHHC5	psi-mi:“MI:0403”(colocalization)	0.710
GOLGA7	ZDHHC5	psi-mi:“MI:0914”(association)	0.710
ZDHHC5	GOLGA7B	psi-mi:“MI:0915”(physical association)	0.650
ZDHHC5	GOLGA7B	psi-mi:“MI:0403”(colocalization)	0.650
GYPA	GOLGA7	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
MMAB	PMPCB	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
S	ZDHHC5	psi-mi:“MI:0915”(physical association)	0.400
ZDHHC5	CD320	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
	ZDHHC5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (173): ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Biochemical Activity), ZDHHC5 (Proximity Label-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1QT59, A2VEY9, A8X9H4, D3KZG3, O35412, O35607, O57474, O61366, O93383, P18861, P29415, P34535, P36383, P43322, P49414, P50605, P60571, P91682, Q02297, Q03345, Q05199, Q11069, Q13873, Q14693, Q2THW7, Q2THW9, Q2THX1, Q5R838, Q5RJX2, Q5YCC7, Q64448, Q69ZW3, Q6DR98, Q6H1V1, Q6IMP4, Q6TYA8, Q7TQ69, Q7Z5M5, Q86B91, Q8INR6

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

5 interactions.

A	Effect	B	Mechanism
ZDHHC5	“up-regulates activity”	S1PR1	palmitoylation
ZDHHC5	“down-regulates activity”	EZH2	palmitoylation
TP53	“up-regulates quantity by expression”	ZDHHC5	“transcriptional regulation”
NFY	“up-regulates quantity by expression”	ZDHHC5	“transcriptional regulation”
FYN	“up-regulates quantity by stabilization”	ZDHHC5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SHC-mediated cascade:FGFR4	5	54.4×	4e-06
SHC-mediated cascade:FGFR1	5	49.6×	4e-06
FRS-mediated FGFR4 signaling	5	49.6×	4e-06
FRS-mediated FGFR1 signaling	5	45.7×	4e-06
Signaling by FGFR1 in disease	5	29.3×	2e-05
Constitutive Signaling by Aberrant PI3K in Cancer	6	15.2×	4e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	11.6×	1e-04
RAF/MAP kinase cascade	8	9.8×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	6	20.6×	2e-04
MAPK cascade	5	12.8×	5e-03
positive regulation of cell migration	9	9.3×	2e-04
positive regulation of MAPK cascade	6	8.1×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2184 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57672215:GATTT:G	donor_gain	1.0000
11:57682417:TGCA:T	acceptor_loss	1.0000
11:57682418:GCA:G	acceptor_loss	1.0000
11:57682419:CA:C	acceptor_loss	1.0000
11:57682420:A:AT	acceptor_loss	1.0000
11:57682421:GGT:G	acceptor_gain	1.0000
11:57682544:GTAA:G	donor_loss	1.0000
11:57682545:T:G	donor_loss	1.0000
11:57688505:C:G	acceptor_gain	1.0000
11:57688506:A:AG	acceptor_gain	1.0000
11:57688506:A:AT	acceptor_loss	1.0000
11:57688506:AGCT:A	acceptor_gain	1.0000
11:57688507:G:GG	acceptor_gain	1.0000
11:57688507:GC:G	acceptor_gain	1.0000
11:57688507:GCT:G	acceptor_gain	1.0000
11:57688507:GCTG:G	acceptor_gain	1.0000
11:57688507:GCTGA:G	acceptor_gain	1.0000
11:57688664:AGG:A	donor_loss	1.0000
11:57688665:GG:G	donor_loss	1.0000
11:57688667:TAAG:T	donor_loss	1.0000
11:57692605:CTCTA:C	acceptor_loss	1.0000
11:57692606:TCTA:T	acceptor_loss	1.0000
11:57692607:CTA:C	acceptor_loss	1.0000
11:57692608:TAGGT:T	acceptor_loss	1.0000
11:57692609:A:AG	acceptor_gain	1.0000
11:57692609:A:T	acceptor_loss	1.0000
11:57692609:AG:A	acceptor_gain	1.0000
11:57692610:G:GT	acceptor_gain	1.0000
11:57692610:G:T	acceptor_loss	1.0000
11:57692610:GG:G	acceptor_gain	1.0000

AlphaMissense

4601 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57673149:C:A	A20D	1.000
11:57682500:C:A	N61K	1.000
11:57682500:C:G	N61K	1.000
11:57682502:T:C	F62S	1.000
11:57682528:G:A	G71R	1.000
11:57682528:G:C	G71R	1.000
11:57682528:G:T	G71W	1.000
11:57682529:G:A	G71E	1.000
11:57682529:G:T	G71V	1.000
11:57688546:C:T	P89S	1.000
11:57688547:C:A	P89H	1.000
11:57688552:T:G	Y91D	1.000
11:57688556:A:T	K92I	1.000
11:57688557:A:C	K92N	1.000
11:57688557:A:T	K92N	1.000
11:57688585:C:A	R102S	1.000
11:57688589:T:G	M103R	1.000
11:57688591:A:C	K104Q	1.000
11:57688591:A:G	K104E	1.000
11:57688592:A:C	K104T	1.000
11:57688592:A:T	K104I	1.000
11:57688593:A:C	K104N	1.000
11:57688593:A:T	K104N	1.000
11:57688594:T:A	W105R	1.000
11:57688594:T:C	W105R	1.000
11:57688595:G:C	W105S	1.000
11:57688596:G:C	W105C	1.000
11:57688596:G:T	W105C	1.000
11:57688597:T:A	C106S	1.000
11:57688597:T:C	C106R	1.000

dbSNP variants (sampled 300 via entrez): RS1000013660 (11:57678593 C>A,G), RS1000125999 (11:57670094 A>G), RS1000151027 (11:57684266 C>T), RS1000218276 (11:57669796 T>G), RS1000311952 (11:57676740 C>T), RS1000518350 (11:57670747 C>A,T), RS1000707263 (11:57691084 T>G), RS1001018138 (11:57697349 G>C), RS1001036825 (11:57689661 C>T), RS1001048097 (11:57678543 C>T), RS1001192526 (11:57700212 C>A,T), RS1001206576 (11:57689471 G>A), RS1001229607 (11:57700411 TATA>T), RS1001312641 (11:57683508 T>A), RS1001401682 (11:57694236 C>T)

Disease associations

OMIM: gene MIM:614586 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	Limited	Unknown

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002539_6	Schizophrenia	2.000000e-09
GCST004521_290	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004946_35	Schizophrenia	9.000000e-09
GCST005232_71	Neuroticism	7.000000e-11
GCST006803_71	Schizophrenia	1.000000e-09
GCST007709_290	General factor of neuroticism	3.000000e-09
GCST010796_593	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-10
GCST010796_594	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_595	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_596	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_597	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_598	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_599	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_600	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_601	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_602	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_603	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_604	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST012111_7	Worry too long after an embarrassing experience	4.000000e-11
GCST012114_15	Sociability score	4.000000e-10
GCST012354_38	Anxiety	7.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004327	electrocardiography
EFO:0009589	worry measurement
EFO:0009592	social interaction measurement
EFO:0009863	anxiety measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
coumarin	affects phosphorylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
Temozolomide	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	increases expression, affects cotreatment, affects localization, decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8DH	Ubigene A-549 ZDHHC5 KO	Cancer cell line	Male
CVCL_E0T9	Ubigene HeLa ZDHHC5 KO	Cancer cell line	Female
CVCL_E0ZR	Ubigene NCI-H1299 ZDHHC5 KO	Cancer cell line	Male
CVCL_TZ00	HAP1 ZDHHC5 (-) 1	Cancer cell line	Male
CVCL_TZ01	HAP1 ZDHHC5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety