ZDHHC2

Summary

ZDHHC2 (zDHHC palmitoyltransferase 2, HGNC:18469) is a protein-coding gene on chromosome 8p22, encoding Palmitoyltransferase ZDHHC2 (Q9UIJ5). Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes.

Enables protein homodimerization activity and protein-cysteine S-palmitoyltransferase activity. Involved in several processes, including peptidyl-L-cysteine S-palmitoylation; protein localization to membrane raft; and synapse assembly. Located in Golgi apparatus; endoplasmic reticulum membrane; and plasma membrane. Is active in postsynaptic recycling endosome.

Source: NCBI Gene 51201 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 64 total
• Druggable target: yes
• MANE Select transcript: NM_016353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18469
Approved symbol	ZDHHC2
Name	zDHHC palmitoyltransferase 2
Location	8p22
Locus type	gene with protein product
Status	Approved
Aliases	ZNF372, DHHC2
Ensembl gene	ENSG00000104219
Ensembl biotype	protein_coding
OMIM	618621
Entrez	51201

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000262096, ENST00000517334, ENST00000522184, ENST00000523132, ENST00000929075, ENST00000955295, ENST00000955296, ENST00000955297

RefSeq mRNA: 3 — MANE Select: NM_016353 NM_001362988, NM_001362989, NM_016353

CCDS: CCDS47810

Canonical transcript exons

ENST00000262096 — 13 exons

Exon	Start	End
ENSE00000681869	17195504	17195624
ENSE00000681874	17197582	17197651
ENSE00000681898	17205655	17205775
ENSE00000681918	17207960	17208092
ENSE00000681964	17215237	17215349
ENSE00000681984	17217172	17217246
ENSE00000888737	17186331	17186425
ENSE00001295698	17210388	17210480
ENSE00001299065	17220256	17224799
ENSE00001312713	17209932	17210058
ENSE00001541415	17156482	17156853
ENSE00001679480	17198381	17198413
ENSE00003658337	17184789	17184815

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8373 / max 261.2606, expressed in 1738 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87529	13.4713	1697
87527	3.9982	1433
87524	1.3663	684
87523	0.3655	178
87528	0.2704	107
87530	0.2226	60
87526	0.0767	17
87525	0.0663	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.36	gold quality
pigmented layer of retina	UBERON:0001782	96.22	gold quality
epithelial cell of pancreas	CL:0000083	95.47	gold quality
tibialis anterior	UBERON:0001385	95.46	gold quality
ileal mucosa	UBERON:0000331	94.70	gold quality
kidney epithelium	UBERON:0004819	94.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.78	gold quality
biceps brachii	UBERON:0001507	93.72	gold quality
dorsal root ganglion	UBERON:0000044	93.65	gold quality
renal medulla	UBERON:0000362	93.54	gold quality
deltoid	UBERON:0001476	93.52	gold quality
germinal epithelium of ovary	UBERON:0001304	93.33	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.26	gold quality
adrenal tissue	UBERON:0018303	93.22	gold quality
trigeminal ganglion	UBERON:0001675	93.08	gold quality
corpus epididymis	UBERON:0004359	92.94	gold quality
body of tongue	UBERON:0011876	92.94	gold quality
islet of Langerhans	UBERON:0000006	92.80	gold quality
caput epididymis	UBERON:0004358	92.57	gold quality
vastus lateralis	UBERON:0001379	92.32	gold quality
corpus callosum	UBERON:0002336	91.99	gold quality
skeletal muscle tissue	UBERON:0001134	91.51	gold quality
bone marrow	UBERON:0002371	91.33	gold quality
quadriceps femoris	UBERON:0001377	91.31	gold quality
tongue	UBERON:0001723	91.24	gold quality
trabecular bone tissue	UBERON:0002483	91.22	gold quality
seminal vesicle	UBERON:0000998	91.07	gold quality
epithelium of nasopharynx	UBERON:0001951	90.99	gold quality
endothelial cell	CL:0000115	90.91	gold quality
oviduct epithelium	UBERON:0004804	90.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.12
E-MTAB-4850	no	385.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YBX3, ZBTB32

miRNA regulators (miRDB)

163 targeting ZDHHC2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 10)

• Identification of CKAP4/p63 as a substrate of DHHC2, a putative tumor suppressor. (PMID:18296695)
• DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151 (PMID:18508921)
• DHHC2-mediated palmitoylation of CKAP4 has a role in opposing cancer-related cellular behaviors. (PMID:19144824)
• Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7 family-binding protein. (PMID:21343290)
• The palmitoyl transferase DHHC2 targets a dynamic membrane cycling pathway: regulation by a C-terminal domain (PMID:21471008)
• DHHC2 localizes primarily to the endoplasmic reticulum and Golgi apparatus suggesting that it is involved in S-acylation of newly-synthesized or recycling Lck involved in T cell signalling. (PMID:22034844)
• reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients (PMID:23457560)
• These results suggest an important role for ZDHHC2 as a tumor suppressor in metastasis and recurrence of HCC. (PMID:24995331)
• Fine-mapping of ZDHHC2 identifies risk variants for schizophrenia in the Han Chinese population. (PMID:32180374)
• Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis. (PMID:33488612)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	zdhhc2	ENSDARG00000034757
mus_musculus	Zdhhc2	ENSMUSG00000039470
rattus_norvegicus	Zdhhc2	ENSRNOG00000022686
drosophila_melanogaster	Dnz1	FBGN0027453
drosophila_melanogaster	CG1407	FBGN0033474
drosophila_melanogaster	CG17287	FBGN0034202
caenorhabditis_elegans	dhhc-7	WBGENE00007637
caenorhabditis_elegans	dhhc-12	WBGENE00010323
caenorhabditis_elegans	dhhc-2	WBGENE00012948
caenorhabditis_elegans		WBGENE00014075
caenorhabditis_elegans		WBGENE00016620
caenorhabditis_elegans		WBGENE00020066

Paralogs (17): ZDHHC6 (ENSG00000023041), ZDHHC15 (ENSG00000102383), ZDHHC4 (ENSG00000136247), 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 ZDHHC2 — Q9UIJ5 (reviewed: Q9UIJ5)

Alternative names: Acyltransferase ZDHHC2, Reduced expression associated with metastasis protein, Reduced expression in cancer protein, Zinc finger DHHC domain-containing protein 2, Zinc finger protein 372

All UniProt accessions (4): A0A140VKD9, A0A1Y8EM58, E5RFZ7, Q9UIJ5

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes. Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA. In the nervous system, plays a role in long term synaptic potentiation by palmitoylating AKAP5 through which it regulates protein trafficking from the dendritic recycling endosomes to the plasma membrane and controls both structural and functional plasticity at excitatory synapses. In dendrites, mediates the palmitoylation of DLG4 when synaptic activity decreases and induces synaptic clustering of DLG4 and associated AMPA-type glutamate receptors. Also mediates the de novo and turnover palmitoylation of RGS7BP, a shuttle for Gi/o-specific GTPase-activating proteins/GAPs, promoting its localization to the plasma membrane in response to the activation of G protein-coupled receptors. Through the localization of these GTPase-activating proteins/GAPs, it also probably plays a role in G protein-coupled receptors signaling in neurons. Also probably plays a role in cell adhesion by palmitoylating CD9 and CD151 to regulate their expression and function. Palmitoylates the endoplasmic reticulum protein CKAP4 and regulates its localization to the plasma membrane. Could also palmitoylate LCK and regulate its localization to the plasma membrane. (Microbial infection) Promotes Chikungunya virus (CHIKV) replication by mediating viral nsp1 palmitoylation.

Subunit / interactions. Monomer. Homodimer. The monomeric form has a higher catalytic activity.

Subcellular location. Postsynaptic density. Postsynaptic recycling endosome membrane. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Ubiquitously expressed. Reduced expression in colorectal cancers with liver metastasis.

Post-translational modifications. Autopalmitoylated.

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

Similarity. Belongs to the DHHC palmitoyltransferase family.

RefSeq proteins (3): NP_001349917, NP_001349918, NP_057437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001594	Palmitoyltrfase_DHHC	Domain
IPR039859	PFA4/ZDH16/20/ERF2-like	Family

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), 3 shown:

• L-cysteinyl-[protein] + hexadecanoyl-CoA = S-hexadecanoyl-L-cysteinyl-[protein] + CoA (RHEA:36683)
• L-cysteinyl-[protein] + tetradecanoyl-CoA = S-tetradecanoyl-L-cysteinyl-[protein] + CoA (RHEA:59736)
• L-cysteinyl-[protein] + octadecanoyl-CoA = S-octadecanoyl-L-cysteinyl-[protein] + CoA (RHEA:59740)

UniProt features (22 total): topological domain 5, transmembrane region 4, region of interest 2, short sequence motif 2, sequence variant 2, mutagenesis site 2, chain 1, domain 1, compositionally biased region 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIJ5-F1	82.91	0.71

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): 157 (s-palmitoyl cysteine intermediate)

Post-translational modifications (1): 341

Mutagenesis-validated functional residues (2):

Position	Phenotype
154–155	loss of protein-cysteine s-palmitoyltransferase activity.
157	loss of protein-cysteine s-palmitoyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5683826	Surfactant metabolism
R-HSA-9694548	Maturation of spike protein

MSigDB gene sets: 303 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MODULE_255, GOBP_SYNAPSE_ASSEMBLY, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PEPTIDYL_CYSTEINE_MODIFICATION, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING

GO Biological Process (16): protein targeting to membrane (GO:0006612), synapse assembly (GO:0007416), synaptic vesicle maturation (GO:0016188), peptidyl-L-cysteine S-palmitoylation (GO:0018230), regulation of cell-cell adhesion (GO:0022407), regulation of protein catabolic process (GO:0042176), regulation of neuronal synaptic plasticity (GO:0048168), protein localization to plasma membrane (GO:0072659), postsynaptic neurotransmitter receptor cycle (GO:0099630), regulation of postsynaptic neurotransmitter receptor diffusion trapping (GO:0150054), positive regulation of long-term synaptic potentiation (GO:1900273), protein localization to membrane raft (GO:1903044), regulation of protein localization to plasma membrane (GO:1903076), protein localization to postsynaptic membrane (GO:1903539), positive regulation of AMPA glutamate receptor clustering (GO:1904719), positive regulation of endosome to plasma membrane protein transport (GO:1905751)

GO Molecular Function (7): palmitoyltransferase activity (GO:0016409), protein-cysteine S-myristoyltransferase activity (GO:0019705), protein-cysteine S-palmitoyltransferase activity (GO:0019706), protein homodimerization activity (GO:0042803), protein-cysteine S-stearoyltransferase activity (GO:0140439), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (13): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), recycling endosome membrane (GO:0055038), postsynaptic recycling endosome (GO:0098837), postsynaptic recycling endosome membrane (GO:0098944), glutamatergic synapse (GO:0098978), endosome (GO:0005768), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of proteins	1
Translation of Structural Proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein localization to membrane	3
protein-cysteine S-acyltransferase activity	3
endomembrane system	3
protein localization to cell periphery	2
postsynapse	2
cytoplasm	2
intracellular membrane-bounded organelle	2
recycling endosome	2
protein targeting	1
establishment of protein localization to membrane	1
nervous system development	1
cell junction assembly	1
synapse organization	1
vesicle organization	1
developmental maturation	1
peptidyl-S-diacylglycerol-L-cysteine biosynthetic process from peptidyl-cysteine	1
protein palmitoylation	1
regulation of cell adhesion	1
cell-cell adhesion	1
regulation of catabolic process	1
protein catabolic process	1
regulation of protein metabolic process	1
regulation of synaptic plasticity	1
establishment of localization in cell	1
neurotransmitter receptor cycle	1
regulation of cellular localization	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor diffusion trapping	1
regulation of receptor localization to synapse	1
positive regulation of synaptic transmission	1
long-term synaptic potentiation	1
regulation of long-term synaptic potentiation	1
protein localization to plasma membrane	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
protein localization to postsynapse	1
AMPA glutamate receptor clustering	1
positive regulation of postsynaptic membrane organization	1
positive regulation of receptor clustering	1
regulation of AMPA glutamate receptor clustering	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC2	CKAP4	Q07065	718
ZDHHC2	GOLGA7	Q7Z5G4	616
ZDHHC2	DLG4	P78352	542
ZDHHC2	LYPLA1	O75608	520
ZDHHC2	ASB18	Q6ZVZ8	478
ZDHHC2	RSPRY1	Q96DX4	474
ZDHHC2	LYPLA2	O95372	472
ZDHHC2	PPT1	P50897	471
ZDHHC2	TUSC3	Q13454	458
ZDHHC2	ASB16	Q96NS5	455
ZDHHC2	MYLIP	Q8WY64	452
ZDHHC2	AKAP5	P24588	448
ZDHHC2	ZFP36L2	P47974	447
ZDHHC2	ZDHHC13	Q8IUH4	435
ZDHHC2	NRIP3	Q9NQ35	435

IntAct

7 interactions, top by confidence:

A	B	Type	Score
S	ZDHHC2	psi-mi:“MI:0216”(palmitoylation reaction)	0.440
	ZDHHC2	psi-mi:“MI:0915”(physical association)	0.370
MSX2	ZDHHC2	psi-mi:“MI:0915”(physical association)	0.370
MAFB	ZDHHC2	psi-mi:“MI:0915”(physical association)	0.370
SLC39A4	GPR39	psi-mi:“MI:0914”(association)	0.350
TMEM169	PTGES3L-AARSD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ZDHHC2 (Proximity Label-MS), ZDHHC2 (Proximity Label-MS), ZDHHC2 (Proximity Label-MS), S (Biochemical Activity), ZDHHC2 (Proximity Label-MS), ZDHHC2 (Proximity Label-MS), ZDHHC2 (Co-fractionation), ZDHHC2 (Two-hybrid), ZDHHC2 (Two-hybrid)

ESM2 similar proteins: A0A0R4IDP3, A0A0R4IF99, A0PK84, B0S5D5, B1H1H3, E7F021, E7F587, F1QAM1, F1QGD2, F1QHM7, F1QX91, F1QXD3, P59267, Q0VC89, Q10L01, Q2TGI8, Q2TGJ1, Q2TGJ4, Q4R7E2, Q500Z2, Q58CU4, Q58DT3, Q5BLG4, Q5FVR1, Q5FWL7, Q5M757, Q5Y5T3, Q6DHI1, Q6FSS4, Q750R7, Q75AW7, Q76IC6, Q8BGJ0, Q8N966, Q8VYP5, Q8WVZ1, Q91WU6, Q923G5, Q93VV0, Q94C49

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

4 interactions.

A	Effect	B	Mechanism
ZDHHC2	“up-regulates activity”	DLG4	palmitoylation
ZDHHC2	“up-regulates activity”	AKAP5	palmitoylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2407 predictions. Top by Δscore:

Variant	Effect	Δscore
8:17156850:ATAGG:A	donor_loss	1.0000
8:17156851:TAGG:T	donor_loss	1.0000
8:17156852:AGG:A	donor_loss	1.0000
8:17184787:A:AG	acceptor_gain	1.0000
8:17184788:G:GG	acceptor_gain	1.0000
8:17184788:GT:G	acceptor_gain	1.0000
8:17184814:AGGTA:A	donor_loss	1.0000
8:17184815:GGTA:G	donor_loss	1.0000
8:17184816:G:GC	donor_loss	1.0000
8:17185038:GCTT:G	donor_gain	1.0000
8:17186324:A:AG	acceptor_gain	1.0000
8:17186325:TTTTA:T	acceptor_loss	1.0000
8:17186326:TTTA:T	acceptor_loss	1.0000
8:17186327:TTAG:T	acceptor_loss	1.0000
8:17186328:TAGTT:T	acceptor_loss	1.0000
8:17186329:A:AG	acceptor_gain	1.0000
8:17186329:A:G	acceptor_loss	1.0000
8:17186329:AGTT:A	acceptor_gain	1.0000
8:17186330:G:A	acceptor_loss	1.0000
8:17186330:G:GC	acceptor_gain	1.0000
8:17186330:GT:G	acceptor_gain	1.0000
8:17186330:GTT:G	acceptor_gain	1.0000
8:17186330:GTTG:G	acceptor_gain	1.0000
8:17186330:GTTGT:G	acceptor_gain	1.0000
8:17186421:AAGAA:A	donor_gain	1.0000
8:17186422:AGAA:A	donor_gain	1.0000
8:17186423:GAA:G	donor_gain	1.0000
8:17186423:GAAG:G	donor_gain	1.0000
8:17186423:GAAGT:G	donor_loss	1.0000
8:17186424:AA:A	donor_gain	1.0000

AlphaMissense

2433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:17197593:T:C	C129R	1.000
8:17197594:G:A	C129Y	1.000
8:17197595:T:G	C129W	1.000
8:17197614:A:G	K136E	1.000
8:17197616:A:C	K136N	1.000
8:17197616:A:T	K136N	1.000
8:17197618:C:A	P137Q	1.000
8:17197623:C:A	R139S	1.000
8:17197624:G:C	R139P	1.000
8:17197629:C:G	H141D	1.000
8:17197635:T:C	C143R	1.000
8:17197636:G:A	C143Y	1.000
8:17197637:C:G	C143W	1.000
8:17198382:T:C	C149R	1.000
8:17198397:G:C	D154H	1.000
8:17198398:A:C	D154A	1.000
8:17198398:A:T	D154V	1.000
8:17198400:C:A	H155N	1.000
8:17198400:C:G	H155D	1.000
8:17198401:A:C	H155P	1.000
8:17198402:T:A	H155Q	1.000
8:17198402:T:G	H155Q	1.000
8:17198403:C:G	H156D	1.000
8:17198406:T:C	C157R	1.000
8:17205667:T:G	C163W	1.000
8:17205669:T:A	V164D	1.000
8:17208032:A:C	S224R	1.000
8:17208034:C:A	S224R	1.000
8:17208034:C:G	S224R	1.000
8:17209979:T:C	F260L	1.000

dbSNP variants (sampled 300 via entrez): RS1000031578 (8:17175948 C>T), RS1000045642 (8:17173992 G>A,C), RS1000049362 (8:17215118 G>A), RS1000069324 (8:17220745 T>C), RS1000094245 (8:17205356 G>A), RS1000120198 (8:17155428 A>G), RS1000122531 (8:17223669 A>C,G), RS1000160974 (8:17184403 T>A), RS1000161960 (8:17167363 T>C), RS1000222091 (8:17186497 A>G), RS1000240191 (8:17180824 T>C), RS1000263006 (8:17205625 T>C), RS1000324567 (8:17176587 A>G), RS1000330027 (8:17171621 C>G), RS1000339806 (8:17159553 T>C)

Disease associations

OMIM: gene MIM:618621 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003805_5	Diastolic blood pressure response to hydrochlorothiazide in hypertension	4.000000e-07
GCST003807_5	Systolic blood pressure response to hydrochlorothiazide in hypertension	4.000000e-07
GCST004946_93	Schizophrenia	3.000000e-12
GCST007201_328	Schizophrenia	4.000000e-08
GCST007201_93	Schizophrenia	2.000000e-10
GCST010991_6	Parkinson’s disease	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006945	diastolic blood pressure change measurement
EFO:0006944	systolic blood pressure change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169204 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 5 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.23	IC50	590	nM	CHEMBL5201039
5.70	IC50	2020	nM	CHEMBL118417
5.70	IC50	2020	nM	CHEMBL5186633
5.58	IC50	2660	nM	CHEMBL5199102

PubChem BioAssay actives

4 with measured affinity, of 13 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(cyanomethyl)-N-tetradecylprop-2-enamide	1875528: Inhibition of human myc-His6-tagged zDHHC2 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	0.5900	uM
phenyl (Z)-4-oxo-4-(tetradecylamino)but-2-enoate	1875528: Inhibition of human myc-His6-tagged zDHHC2 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	2.0200	uM
2-bromohexadecanoic acid	1875528: Inhibition of human myc-His6-tagged zDHHC2 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	2.0200	uM
cyanomethyl (Z)-4-oxo-4-(tetradecylamino)but-2-enoate	1875528: Inhibition of human myc-His6-tagged zDHHC2 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	2.6600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	decreases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5131021	Binding	Inhibition of human myc-His6-tagged zDHHC2 expressed in HEK293T cells at 10 uM using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmi	Charting the Chemical Space of Acrylamide-Based Inhibitors of zDHHC20. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TY83	HAP1 ZDHHC2 (-) 1	Cancer cell line	Male
CVCL_TY84	HAP1 ZDHHC2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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