ZDHHC22

Summary

ZDHHC22 (zDHHC palmitoyltransferase 22, HGNC:20106) is a protein-coding gene on chromosome 14q24.3, encoding Palmitoyltransferase ZDHHC22 (Q8N966). 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. Located in Golgi apparatus; endoplasmic reticulum; and plasma membrane.

Source: NCBI Gene 283576 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_174976

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20106
Approved symbol	ZDHHC22
Name	zDHHC palmitoyltransferase 22
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177108
Ensembl biotype	protein_coding
Entrez	283576

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000319374, ENST00000555327, ENST00000555389, ENST00000924336, ENST00000924337, ENST00000924338, ENST00000924339, ENST00000924340, ENST00000924341

RefSeq mRNA: 2 — MANE Select: NM_174976 NM_001364172, NM_174976

CCDS: CCDS45140

Canonical transcript exons

ENST00000319374 — 3 exons

Exon	Start	End
ENSE00001240053	77131270	77133948
ENSE00001240060	77139213	77139752
ENSE00001719842	77141603	77141791

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 90.73.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1654 / max 318.7009, expressed in 390 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144215	4.1258	375
144214	0.7863	211
144212	0.1362	78
144213	0.0777	53
144209	0.0394	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	90.73	gold quality
prefrontal cortex	UBERON:0000451	89.71	gold quality
primary visual cortex	UBERON:0002436	89.25	gold quality
right frontal lobe	UBERON:0002810	88.96	gold quality
anterior cingulate cortex	UBERON:0009835	88.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.08	gold quality
hypothalamus	UBERON:0001898	87.55	gold quality
frontal cortex	UBERON:0001870	87.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.46	gold quality
neocortex	UBERON:0001950	87.35	gold quality
ganglionic eminence	UBERON:0004023	85.59	gold quality
cerebral cortex	UBERON:0000956	85.57	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.95	gold quality
middle temporal gyrus	UBERON:0002771	84.61	gold quality
amygdala	UBERON:0001876	83.69	gold quality
occipital lobe	UBERON:0002021	83.62	gold quality
Ammon’s horn	UBERON:0001954	82.95	gold quality
cortical plate	UBERON:0005343	81.99	gold quality
superior frontal gyrus	UBERON:0002661	81.77	gold quality
forebrain	UBERON:0001890	81.50	gold quality
brain	UBERON:0000955	80.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.66	gold quality
temporal lobe	UBERON:0001871	80.53	gold quality
cerebellar hemisphere	UBERON:0002245	80.15	gold quality
cerebellar cortex	UBERON:0002129	80.08	gold quality
substantia nigra	UBERON:0002038	80.04	gold quality
cerebellar vermis	UBERON:0004720	79.89	silver quality
cerebellum	UBERON:0002037	78.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	78.69	gold quality
postcentral gyrus	UBERON:0002581	78.65	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	91.16
E-MTAB-6058	no	12.74
E-ANND-3	no	1.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting ZDHHC22, 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-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4524A-3P	99.72	66.85	2406

Literature-anchored findings (GeneRIF, showing 3)

• Taken together, our results suggest that palmitoylation by ZDHHC22 at C241 in the CCN3 TSP1 domain may be required for the secretion of CCN3. Aberrant palmitoylation induces intracellular accumulation of CCN3, inhibiting neuronal axon growth. (PMID:29287726)
• NS1-mediated upregulation of ZDHHC22 acyltransferase in influenza a virus infected cells. (PMID:33629465)
• ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance. (PMID:35541896)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	zdhhc22	ENSDARG00000075170
mus_musculus	Zdhhc22	ENSMUSG00000048483
rattus_norvegicus	Zdhhc22	ENSRNOG00000011285
drosophila_melanogaster	CG18810	FBGN0042133
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), ZDHHC20 (ENSG00000180776), ZDHHC23 (ENSG00000184307), ZDHHC9 (ENSG00000188706), ZDHHC11 (ENSG00000188818), ZDHHC18 (ENSG00000204160), ZDHHC11B (ENSG00000206077)

Protein

Protein identifiers

Palmitoyltransferase ZDHHC22 — Q8N966 (reviewed: Q8N966)

Alternative names: Zinc finger DHHC domain-containing protein 22

All UniProt accessions (3): Q8N966, G3V259, G3V3N3

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. Catalyzes the palmitoylation of KCNMA1, regulating localization of KCNMA1 to the plasma membrane. Might also mediate palmitoylation of CNN3.

Subunit / interactions. Interacts with CNN3.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Widely expressed.

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

Similarity. Belongs to the DHHC palmitoyltransferase family.

RefSeq proteins (2): NP_001351101, NP_777636* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000731	SSD	Domain
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 (14 total): topological domain 5, transmembrane region 5, chain 1, domain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N966-F1	88.21	0.63

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): 111 (s-palmitoyl cysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): RRAGTTGT_UNKNOWN, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, chr14q24, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, AACTTT_UNKNOWN, GOBP_PROTEIN_ACYLATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_PALMITOYLATION, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_S_ACYLTRANSFERASE_ACTIVITY

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 (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:

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
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC22	ZDHHC23	Q8IYP9	748
ZDHHC22	ZDHHC11	Q9H8X9	693
ZDHHC22	ZDHHC4	Q9NPG8	690
ZDHHC22	ZDHHC13	Q8IUH4	686
ZDHHC22	ZDHHC17	Q8IUH5	669
ZDHHC22	ZC2HC1B	Q5TFG8	646
ZDHHC22	ZDHHC12	Q96GR4	645
ZDHHC22	ZDHHC19	Q8WVZ1	632
ZDHHC22	ZDHHC15	Q96MV8	630
ZDHHC22	FAM163B	P0C2L3	624
ZDHHC22	ZDHHC1	Q8WTX9	621
ZDHHC22	ZDHHC8	Q9ULC8	610
ZDHHC22	ZDHHC5	Q9C0B5	580
ZDHHC22	SEC22C	Q9BRL7	542
ZDHHC22	ZDHHC20	Q5W0Z9	520

IntAct

56 interactions, top by confidence:

A	B	Type	Score
ZDHHC22	TRIM59	psi-mi:“MI:0915”(physical association)	0.830
TRIM59	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.830
ZDHHC22	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
LDLRAD4	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	RPRM	psi-mi:“MI:0915”(physical association)	0.560
CD79A	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.560
PVR	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	CLEC4D	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	FCRL2	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
TMEM88	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC22	GPX8	psi-mi:“MI:0915”(physical association)	0.560
	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.370
CCL1	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.370
LTA	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.370
BMP2K	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.370
ZDHHC22	ARL6IP5	psi-mi:“MI:0914”(association)	0.350
ZDHHC22	LDLRAD4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): TRIM59 (Two-hybrid), TRIM59 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), ZDHHC22 (Two-hybrid), RPRM (Two-hybrid), TMEM86B (Two-hybrid)

ESM2 similar proteins: A0A059XKS9, A0A125YQS6, A0A125YS36, A0A7J6K144, A0A7J6K629, A0A7J6K7I9, A0A7J6KE60, A0MQA3, A4HK17, A4I7K1, A5K9W3, A9UYK7, B6KFA9, B9Q0C2, C4YBE4, C5DNL7, L7WGA7, O60503, O83066, O83160, O83544, P51830, P70551, P98999, Q07762, Q0PKV7, Q2PP52, Q383A1, Q388F1, Q39183, Q4DHA1, Q580W5, Q6GV23, Q758T2, Q86G50, Q8BIV7, Q8K4S3, Q8N966, Q9R101, Q9W415

Diamond homologs: A0A0R4IDP3, A0PK84, A2CEX1, A2VEY9, B8A4F0, C8VCL4, E1BLT8, E7FBS9, E7FH11, E9QCD3, F1QAM1, F1QHM7, F1RE57, J9VJ99, O60069, O74384, P0CS66, P0CS67, P0CS68, P0CS69, P59268, Q09701, Q0WQK2, Q10L01, Q2TGI5, Q2TGI8, Q2TGJ1, Q2TGK3, Q2THW0, Q2THW7, Q2THW8, Q2THW9, Q2THX0, Q2THX1, Q4P6L3, Q4WZL8, Q4X251, Q500Z2, Q550R7, Q552M6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1079 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77141598:CTCA:C	donor_loss	1.0000
14:77141599:TCA:T	donor_loss	1.0000
14:77141600:CAC:C	donor_loss	1.0000
14:77141601:A:AC	donor_gain	1.0000
14:77141602:C:CC	donor_gain	1.0000
14:77141602:C:CT	donor_loss	1.0000
14:77141602:CCGAG:C	donor_gain	1.0000
14:77135136:A:T	donor_gain	0.9900
14:77139207:ACTC:A	donor_loss	0.9900
14:77139208:CT:C	donor_loss	0.9900
14:77139209:TCACC:T	donor_loss	0.9900
14:77139210:C:CG	donor_loss	0.9900
14:77139211:ACCGG:A	donor_loss	0.9900
14:77139212:C:CG	donor_loss	0.9900
14:77136559:C:T	acceptor_gain	0.9800
14:77139211:A:AC	donor_gain	0.9800
14:77139212:C:CC	donor_gain	0.9800
14:77141601:AC:A	donor_gain	0.9800
14:77141602:CC:C	donor_gain	0.9800
14:77141602:CCG:C	donor_gain	0.9800
14:77141602:CCGA:C	donor_gain	0.9800
14:77142140:G:GT	donor_gain	0.9600
14:77136559:C:CT	acceptor_gain	0.9500
14:77139748:CATTC:C	acceptor_gain	0.9500
14:77139763:C:T	acceptor_gain	0.9500
14:77140837:T:TA	donor_gain	0.9500
14:77141597:ACT:A	donor_loss	0.9500
14:77139206:CACT:C	donor_loss	0.9400
14:77139764:G:T	acceptor_gain	0.9400
14:77140497:CA:C	donor_gain	0.9400

AlphaMissense

1700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77139361:G:C	F126L	0.999
14:77139361:G:T	F126L	0.999
14:77139363:A:G	F126L	0.999
14:77139406:A:C	C111W	0.998
14:77139408:A:G	C111R	0.998
14:77133889:C:G	G196R	0.997
14:77139407:C:T	C111Y	0.997
14:77139409:G:C	H110Q	0.997
14:77139409:G:T	H110Q	0.997
14:77139309:C:G	G144R	0.996
14:77139328:G:C	C137W	0.996
14:77139330:A:G	C137R	0.996
14:77139349:G:C	C130W	0.996
14:77139373:G:C	N122K	0.996
14:77139373:G:T	N122K	0.996
14:77139388:G:C	C117W	0.996
14:77133878:G:C	C199W	0.995
14:77133888:C:T	G196D	0.995
14:77133901:A:G	W192R	0.995
14:77133901:A:T	W192R	0.995
14:77139362:A:G	F126S	0.995
14:77139374:T:A	N122I	0.995
14:77139407:C:A	C111F	0.995
14:77139411:G:C	H110D	0.995
14:77139412:A:C	H109Q	0.995
14:77139412:A:T	H109Q	0.995
14:77139329:C:T	C137Y	0.994
14:77139351:A:G	C130R	0.994
14:77139362:A:C	F126C	0.994
14:77139386:A:T	I118N	0.994

dbSNP variants (sampled 300 via entrez): RS1000305382 (14:77140158 G>C), RS1000338886 (14:77133575 T>C), RS1000467899 (14:77139964 G>C,T), RS1000659561 (14:77139876 C>A,G,T), RS1001069338 (14:77138362 C>G,T), RS1001323045 (14:77137361 T>C), RS1001475072 (14:77143079 A>G), RS1001740636 (14:77141320 G>T), RS1001909967 (14:77135296 C>T), RS1002005856 (14:77131901 T>C), RS1002243704 (14:77134981 A>C), RS1002382391 (14:77141528 A>C,G), RS1002663540 (14:77131888 T>C), RS1002879375 (14:77135415 A>G), RS1002914697 (14:77137876 G>A)

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

4 associations (top):

Study	Trait	p-value
GCST002288_1	Large artery stroke	4.000000e-07
GCST004070_19	Cerebrospinal P-tau181p levels	4.000000e-06
GCST007327_200	Smoking status (ever vs never smokers)	5.000000e-08
GCST010572_6	Sweet taste preference	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004763	p-tau measurement
EFO:0004318	smoking behavior
EFO:0010156	sweet liking measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Tretinoin	affects expression	1
Valproic Acid	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_TY88	HAP1 ZDHHC22 (-) 1	Cancer cell line	Male
CVCL_TY89	HAP1 ZDHHC22 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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