ZDHHC23

Summary

ZDHHC23 (zDHHC palmitoyltransferase 23, HGNC:28654) is a protein-coding gene on chromosome 3q13.31, encoding Palmitoyltransferase ZDHHC23 (Q8IYP9). Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes.

Predicted to enable protein-cysteine S-palmitoyltransferase activity. Involved in protein localization to plasma membrane and protein palmitoylation. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum.

Source: NCBI Gene 254887 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_001320466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28654
Approved symbol	ZDHHC23
Name	zDHHC palmitoyltransferase 23
Location	3q13.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC42530
Ensembl gene	ENSG00000184307
Ensembl biotype	protein_coding
OMIM	617334
Entrez	254887

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000330212, ENST00000478793, ENST00000488129, ENST00000491556, ENST00000496083, ENST00000498275, ENST00000638807, ENST00000869326, ENST00000869327, ENST00000932004, ENST00000954481, ENST00000954482

RefSeq mRNA: 5 — MANE Select: NM_001320466 NM_001320466, NM_001320467, NM_001320468, NM_001363952, NM_173570

CCDS: CCDS33827, CCDS87122, CCDS93341

Canonical transcript exons

ENST00000638807 — 5 exons

Exon	Start	End
ENSE00001294860	113953700	113954410
ENSE00001310642	113956339	113956506
ENSE00001936191	113948686	113948963
ENSE00003807864	113958363	113963373
ENSE00003919025	113948013	113948190

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 91.00.

FANTOM5 (CAGE): breadth broad, TPM avg 0.3264 / max 21.6521, expressed in 184 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37985	0.1632	97
37984	0.1459	77
37986	0.0173	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	91.00	gold quality
ileal mucosa	UBERON:0000331	89.21	gold quality
rectum	UBERON:0001052	85.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.45	gold quality
mucosa of transverse colon	UBERON:0004991	85.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.13	gold quality
colonic mucosa	UBERON:0000317	82.58	gold quality
middle temporal gyrus	UBERON:0002771	82.28	gold quality
left testis	UBERON:0004533	82.27	gold quality
right testis	UBERON:0004534	82.19	gold quality
metanephros cortex	UBERON:0010533	81.69	gold quality
testis	UBERON:0000473	81.57	gold quality
left lobe of thyroid gland	UBERON:0001120	80.92	gold quality
prefrontal cortex	UBERON:0000451	80.65	gold quality
right uterine tube	UBERON:0001302	80.56	gold quality
right lobe of thyroid gland	UBERON:0001119	80.41	gold quality
transverse colon	UBERON:0001157	80.32	gold quality
thyroid gland	UBERON:0002046	80.15	gold quality
right frontal lobe	UBERON:0002810	79.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.58	gold quality
frontal cortex	UBERON:0001870	79.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	79.05	gold quality
superior frontal gyrus	UBERON:0002661	78.71	gold quality
neocortex	UBERON:0001950	78.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.66	gold quality
buccal mucosa cell	CL:0002336	77.96	silver quality
nucleus accumbens	UBERON:0001882	77.83	gold quality
cortex of kidney	UBERON:0001225	77.74	gold quality
body of pancreas	UBERON:0001150	77.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting ZDHHC23, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	zdhhc23b	ENSDARG00000003899
danio_rerio	zdhhc23a	ENSDARG00000029039
mus_musculus	Zdhhc23	ENSMUSG00000036304
rattus_norvegicus	Zdhhc23	ENSRNOG00000060348
drosophila_melanogaster	GABPI	FBGN0031495
caenorhabditis_elegans	dhhc-12	WBGENE00010323
caenorhabditis_elegans	dhhc-2	WBGENE00012948
caenorhabditis_elegans		WBGENE00016620

Paralogs (17): ZDHHC6 (ENSG00000023041), ZDHHC15 (ENSG00000102383), ZDHHC2 (ENSG00000104219), ZDHHC4 (ENSG00000136247), ZDHHC7 (ENSG00000153786), ZDHHC1 (ENSG00000159714), ZDHHC12 (ENSG00000160446), ZDHHC3 (ENSG00000163812), ZDHHC19 (ENSG00000163958), ZDHHC14 (ENSG00000175048), ZDHHC21 (ENSG00000175893), ZDHHC22 (ENSG00000177108), ZDHHC20 (ENSG00000180776), ZDHHC9 (ENSG00000188706), ZDHHC11 (ENSG00000188818), ZDHHC18 (ENSG00000204160), ZDHHC11B (ENSG00000206077)

Protein

Protein identifiers

Palmitoyltransferase ZDHHC23 — Q8IYP9 (reviewed: Q8IYP9)

Alternative names: Zinc finger DHHC domain-containing protein 23

All UniProt accessions (6): A0A1W2PRJ8, B3KXV3, C9JPJ8, E9PAP7, Q8IYP9, H7C4L2

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes. Palmitoyltransferase that mediates palmitoylation of KCNMA1, regulating localization of KCNMA1 to the plasma membrane. May be involved in NOS1 regulation and targeting to the synaptic membrane.

Subunit / interactions. Interacts with NOS1.

Subcellular location. Golgi apparatus membrane. Golgi apparatus. trans-Golgi network membrane.

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

Similarity. Belongs to the DHHC palmitoyltransferase family.

RefSeq proteins (5): NP_001307395, NP_001307396, NP_001307397, NP_001350881, NP_775841 (=MANE)

Domains & families (InterPro)

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

Pfam: PF01529

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (23 total): topological domain 8, transmembrane region 7, sequence variant 4, chain 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYP9-F1	79.19	0.51

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): 289 (s-palmitoyl cysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 120 (showing top): GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_PROTEIN_ACYLATION, PIT1_Q6, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_PALMITOYLATION, ACEVEDO_LIVER_CANCER_UP, GOMF_S_ACYLTRANSFERASE_ACTIVITY, AAGCACA_MIR218

GO Biological Process (3): protein targeting to membrane (GO:0006612), protein palmitoylation (GO:0018345), protein localization to plasma membrane (GO:0072659)

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

GO Cellular Component (4): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
protein targeting	1
establishment of protein localization to membrane	1
protein lipidation	1
protein acylation	1
protein localization to membrane	1
protein localization to cell periphery	1
palmitoyltransferase activity	1
protein-cysteine S-acyltransferase activity	1
binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC23	ZDHHC22	Q8N966	748
ZDHHC23	ZFP69	Q49AA0	657
ZDHHC23	ZDHHC11	Q9H8X9	553
ZDHHC23	SULT6B1	Q6IMI4	487
ZDHHC23	LYPLA2	O95372	475
ZDHHC23	GK5	Q6ZS86	463
ZDHHC23	LYPLA1	O75608	450
ZDHHC23	ZDHHC24	Q6UX98	441
ZDHHC23	ARHGEF10L	Q9HCE6	418
ZDHHC23	ZDHHC6	Q9H6R6	406
ZDHHC23	TMCO2	Q7Z6W1	402
ZDHHC23	TTC39A	Q5SRH9	400
ZDHHC23	ZDHHC17	Q8IUH5	397
ZDHHC23	LRCH2	Q5VUJ6	375
ZDHHC23	SMAP2	Q8WU79	373

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ZDHHC23	GLIS1	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC23	GAPDHS	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
	ZDHHC23	psi-mi:“MI:0915”(physical association)	0.370
ZDHHC23	VPS37C	psi-mi:“MI:0914”(association)	0.350
GLIS1	ZDHHC23	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (80): CST6 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), POF1B (Affinity Capture-MS), LOR (Affinity Capture-MS), NOS1 (Affinity Capture-Western), NOS1 (Reconstituted Complex), ZDHHC23 (Affinity Capture-Western), ZDHHC18 (Affinity Capture-Western), IRS1 (Affinity Capture-MS), MTOR (Affinity Capture-MS), IGF1 (Affinity Capture-MS), INSR (Affinity Capture-MS), INS (Affinity Capture-MS), PIK3CD (Affinity Capture-MS), PIK3CA (Affinity Capture-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1223 predictions. Top by Δscore:

Variant	Effect	Δscore
3:113956327:T:G	acceptor_gain	1.0000
3:113956327:T:TA	acceptor_gain	1.0000
3:113958357:TCCTA:T	acceptor_loss	1.0000
3:113958358:CCTA:C	acceptor_loss	1.0000
3:113958359:CTA:C	acceptor_loss	1.0000
3:113958360:TA:T	acceptor_loss	1.0000
3:113958361:A:AG	acceptor_gain	1.0000
3:113958361:A:AT	acceptor_loss	1.0000
3:113958361:AGCTC:A	acceptor_gain	1.0000
3:113958362:G:GT	acceptor_gain	1.0000
3:113958362:GC:G	acceptor_gain	1.0000
3:113958362:GCT:G	acceptor_gain	1.0000
3:113958362:GCTC:G	acceptor_gain	1.0000
3:113958362:GCTCG:G	acceptor_gain	1.0000
3:113958626:TCTG:T	donor_gain	1.0000
3:113958629:G:GT	donor_gain	1.0000
3:113965360:C:CC	acceptor_gain	1.0000
3:113965362:T:TC	acceptor_gain	1.0000
3:113948964:G:GG	donor_gain	0.9900
3:113956326:A:AG	acceptor_gain	0.9900
3:113956326:AT:A	acceptor_gain	0.9900
3:113956326:ATGCT:A	acceptor_gain	0.9900
3:113956330:T:A	acceptor_gain	0.9900
3:113965355:TCCTC:T	acceptor_gain	0.9900
3:113965356:CCTCC:C	acceptor_gain	0.9900
3:113965357:CTC:C	acceptor_gain	0.9900
3:113965358:TC:T	acceptor_gain	0.9900
3:113965359:CC:C	acceptor_gain	0.9900
3:113965360:C:CA	acceptor_loss	0.9900
3:113965361:T:C	acceptor_gain	0.9900

AlphaMissense

2841 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:113954409:T:A	W291R	0.998
3:113954409:T:C	W291R	0.998
3:113956350:G:A	C295Y	0.998
3:113956351:C:G	C295W	0.998
3:113956353:T:A	V296D	0.998
3:113956376:T:C	F304L	0.998
3:113956378:T:A	F304L	0.998
3:113956378:T:G	F304L	0.998
3:113954361:T:A	C275S	0.997
3:113954361:T:C	C275R	0.997
3:113954362:G:A	C275Y	0.997
3:113954362:G:C	C275S	0.997
3:113954363:C:G	C275W	0.997
3:113954395:A:T	D286V	0.997
3:113954402:T:A	H288Q	0.997
3:113954402:T:G	H288Q	0.997
3:113954403:T:C	C289R	0.997
3:113956349:T:A	C295S	0.997
3:113956349:T:C	C295R	0.997
3:113956350:G:C	C295S	0.997
3:113954362:G:T	C275F	0.996
3:113954371:G:A	C278Y	0.996
3:113954379:T:C	C281R	0.996
3:113954394:G:C	D286H	0.996
3:113954397:C:G	H287D	0.996
3:113956366:T:A	N300K	0.996
3:113956366:T:G	N300K	0.996
3:113954381:T:G	C281W	0.995
3:113954395:A:C	D286A	0.995
3:113954399:T:A	H287Q	0.995

dbSNP variants (sampled 300 via entrez): RS1000045219 (3:113951187 G>C), RS1000254664 (3:113969931 C>T), RS1000366526 (3:113962545 A>C), RS1000471723 (3:113975954 C>G,T), RS1000631629 (3:113968622 T>TTTTG), RS1000677996 (3:113949990 G>A), RS1000707611 (3:113962084 T>G), RS1000748521 (3:113961826 T>C), RS1001003746 (3:113968990 G>A), RS1001015148 (3:113956135 G>A,C), RS1001017634 (3:113949901 T>G), RS1001446095 (3:113974852 C>T), RS1001603189 (3:113976848 A>G), RS1001679163 (3:113951456 C>A), RS1001708121 (3:113969450 A>C)

Disease associations

OMIM: gene MIM:617334 | 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):

Study	Trait	p-value
GCST001473_4	Crohn’s disease and psoriasis	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases 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	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
Temozolomide	decreases expression	1
Fulvestrant	increases methylation	1
Leflunomide	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Quercetin	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Triclosan	decreases expression	1
Cyclosporine	decreases expression	1
Permethrin	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TY90	HAP1 ZDHHC23 (-) 1	Cancer cell line	Male
CVCL_TY91	HAP1 ZDHHC23 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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