ZDHHC19

Summary

ZDHHC19 (zDHHC palmitoyltransferase 19, HGNC:20713) is a protein-coding gene on chromosome 3q29, encoding Palmitoyltransferase ZDHHC19 (Q8WVZ1). Palmitoyltransferase that mediates palmitoylation oproteins, such as RRAS and SQSTM1.

Enables protein-cysteine S-palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation and positive regulation of aggrephagy. Located in Golgi membrane; endoplasmic reticulum; and perinucleolar compartment.

Source: NCBI Gene 131540 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 59 total — 1 pathogenic
• MANE Select transcript: NM_001039617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20713
Approved symbol	ZDHHC19
Name	zDHHC palmitoyltransferase 19
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	MGC33345
Ensembl gene	ENSG00000163958
Ensembl biotype	protein_coding
OMIM	618671
Entrez	131540

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296326, ENST00000397544, ENST00000438232, ENST00000460442, ENST00000465519, ENST00000488508, ENST00000497422

RefSeq mRNA: 1 — MANE Select: NM_001039617 NM_001039617

CCDS: CCDS43190

Canonical transcript exons

ENST00000296326 — 8 exons

Exon	Start	End
ENSE00001653688	196197452	196197725
ENSE00001953287	196211170	196211400
ENSE00003470305	196209376	196209515
ENSE00003536195	196208388	196208560
ENSE00003588277	196198276	196198451
ENSE00003607352	196198789	196198874
ENSE00003609580	196207398	196207503
ENSE00003614591	196210616	196210737

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 96.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1350 / max 113.6734, expressed in 12 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46334	0.1111	4
46332	0.0239	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.53	gold quality
left testis	UBERON:0004533	96.39	gold quality
testis	UBERON:0000473	93.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.90	gold quality
right adrenal gland	UBERON:0001233	85.06	gold quality
left adrenal gland cortex	UBERON:0035825	84.52	gold quality
right adrenal gland cortex	UBERON:0035827	84.12	gold quality
left adrenal gland	UBERON:0001234	84.09	gold quality
adrenal cortex	UBERON:0001235	83.34	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.61	gold quality
right lobe of liver	UBERON:0001114	81.39	gold quality
adrenal gland	UBERON:0002369	81.14	gold quality
left ventricle myocardium	UBERON:0006566	81.08	gold quality
spleen	UBERON:0002106	80.36	gold quality
left ovary	UBERON:0002119	80.08	gold quality
blood	UBERON:0000178	79.09	gold quality
right ovary	UBERON:0002118	78.99	gold quality
sperm	CL:0000019	77.92	silver quality
kidney epithelium	UBERON:0004819	76.59	gold quality
upper arm skin	UBERON:0004263	74.53	gold quality
ovary	UBERON:0000992	73.87	gold quality
myocardium	UBERON:0002349	72.87	gold quality
liver	UBERON:0002107	72.53	gold quality
nucleus accumbens	UBERON:0001882	71.25	gold quality
adrenal tissue	UBERON:0018303	71.24	gold quality
vastus lateralis	UBERON:0001379	71.18	gold quality
upper lobe of left lung	UBERON:0008952	70.98	gold quality
upper lobe of lung	UBERON:0008948	70.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.37	gold quality
hypothalamus	UBERON:0001898	70.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.02

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• The increased palmitoylation of R-Ras cotransfected with DHHC19 is accompanied by an augmented association with membranes as well as with rafts/caveolae. (PMID:20074548)
• Zinc finger Asp-His-His-Cys palmitoyl -acyltransferase 19 accelerates tumor progression through wnt/beta-catenin pathway and is upregulated by miR-940 in osteosarcoma. (PMID:35297315)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zdhhc19	ENSMUSG00000052363
rattus_norvegicus	Zdhhc19	ENSRNOG00000025055
caenorhabditis_elegans		WBGENE00012718

Paralogs (17): ZDHHC6 (ENSG00000023041), ZDHHC15 (ENSG00000102383), ZDHHC2 (ENSG00000104219), ZDHHC4 (ENSG00000136247), ZDHHC7 (ENSG00000153786), ZDHHC1 (ENSG00000159714), ZDHHC12 (ENSG00000160446), ZDHHC3 (ENSG00000163812), ZDHHC14 (ENSG00000175048), ZDHHC21 (ENSG00000175893), ZDHHC22 (ENSG00000177108), ZDHHC20 (ENSG00000180776), ZDHHC23 (ENSG00000184307), ZDHHC9 (ENSG00000188706), ZDHHC11 (ENSG00000188818), ZDHHC18 (ENSG00000204160), ZDHHC11B (ENSG00000206077)

Protein

Protein identifiers

Palmitoyltransferase ZDHHC19 — Q8WVZ1 (reviewed: Q8WVZ1)

Alternative names: Zinc finger DHHC domain-containing protein 19

All UniProt accessions (1): Q8WVZ1

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that mediates palmitoylation oproteins, such as RRAS and SQSTM1. Catalyzes palmitoylation of RRAS, leading to increased cell viability. Acts as a positive regulator of autophagy by mediating palmitoylation of SQSTM1, promoting affinity between SQSTM1 and ATG8 proteins and recruitment of ubiquitinated cargo proteins to autophagosomes. Palmitoyltransferase activity may be crucial for spermatogenesis. (Microbial infection) Promotes Chikungunya virus (CHIKV) replication by mediating viral nsp1 palmitoylation.

Subunit / interactions. Interacts with TEX38; this interaction is essential for ZDHHC19 stability and localization to the plasma membrane.

Subcellular location. Golgi apparatus membrane. Cytoplasm. Perinuclear region. Cell membrane.

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

Similarity. Belongs to the DHHC palmitoyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WVZ1-1	1	yes
Q8WVZ1-2	2
Q8WVZ1-3	3

RefSeq proteins (1): NP_001034706* (*=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 (14 total): transmembrane region 4, splice variant 3, chain 1, sequence variant 1, mutagenesis site 1, domain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVZ1-F1	78.39	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): 142 (s-palmitoyl cysteine intermediate)

Mutagenesis-validated functional residues (1):

Position	Phenotype
142	abolishes palmitoyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_PEPTIDYL_CYSTEINE_MODIFICATION, GOBP_MACROAUTOPHAGY, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_PROTEIN_ACYLATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_PALMITOYLATION, GOBP_POSITIVE_REGULATION_OF_AUTOPHAGY, GOMF_S_ACYLTRANSFERASE_ACTIVITY

GO Biological Process (5): protein targeting to membrane (GO:0006612), peptidyl-L-cysteine S-palmitoylation (GO:0018230), positive regulation of aggrephagy (GO:1905337), aggrephagy (GO:0035973), protein targeting to vacuole involved in autophagy (GO:0071211)

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 (8): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), perinucleolar compartment (GO:0097356), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
endomembrane system	2
intracellular membrane-bounded organelle	2
protein targeting	1
establishment of protein localization to membrane	1
peptidyl-S-diacylglycerol-L-cysteine biosynthetic process from peptidyl-cysteine	1
protein palmitoylation	1
positive regulation of macroautophagy	1
aggrephagy	1
regulation of aggrephagy	1
macroautophagy	1
protein targeting to vacuole	1
autophagy	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
membrane	1
cell periphery	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC19	SMCO1	Q147U7	675
ZDHHC19	ZDHHC22	Q8N966	632
ZDHHC19	WDR53	Q7Z5U6	612
ZDHHC19	FBXO45	P0C2W1	595
ZDHHC19	SLC51A	Q86UW1	582
ZDHHC19	PCYT1A	P49585	575
ZDHHC19	UBXN7	O94888	567
ZDHHC19	TM4SF19	Q96DZ7	538
ZDHHC19	CEP19	Q96LK0	522
ZDHHC19	BDH1	Q02338	504
ZDHHC19	SENP5	Q96HI0	495
ZDHHC19	CLHC1	Q8NHS4	492
ZDHHC19	NCBP2	P52298	477
ZDHHC19	DYNLT2B	Q8WW35	477
ZDHHC19	NRROS	Q86YC3	465

IntAct

4 interactions, top by confidence:

A	B	Type	Score
STAT3	GRB2	psi-mi:“MI:0914”(association)	0.460
ZDHHC19	CPNE7	psi-mi:“MI:0915”(physical association)	0.400
ZDHHC19	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): CPNE7 (Affinity Capture-MS), LGALS7B (Affinity Capture-MS), YOD1 (Affinity Capture-MS), FLG (Affinity Capture-MS), HBB (Affinity Capture-MS), DSC1 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), JUP (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), DSG1 (Affinity Capture-MS), POF1B (Affinity Capture-MS), SBSN (Affinity Capture-MS), CALML5 (Affinity Capture-MS), KPRP (Affinity Capture-MS), TYMP (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, B8A4F0, C8VCL4, E1BLT8, E7F021, E7FBS9, E7FH11, E9PTT0, E9QCD3, F1Q7H8, F1QAM1, F1QXD3, F1R013, F1RE57, J9VJ99, O60069, O74384, O80685, P0CS66, P0CS67, P0CS68, P0CS69, P59267, P59268, Q04629, Q09701, Q0WQK2, Q10L01, Q2TGJ1, Q2TGJ4, Q2TGK3, Q2THW0, Q2THW7, Q2THW8, Q2THW9, Q2THX0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	47
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3242309	GRCh37/hg19 3q29(chr3:195106447-197846145)x3	Pathogenic

SpliceAI

1486 predictions. Top by Δscore:

Variant	Effect	Δscore
3:196208357:T:TA	donor_gain	1.0000
3:196208362:T:A	donor_gain	1.0000
3:196208369:T:TA	donor_gain	1.0000
3:196208370:C:A	donor_gain	1.0000
3:196211168:A:AC	donor_gain	1.0000
3:196211169:C:CC	donor_gain	1.0000
3:196207392:GCGTA:G	donor_loss	0.9900
3:196207393:CGTA:C	donor_loss	0.9900
3:196207394:GTACC:G	donor_loss	0.9900
3:196207395:TACC:T	donor_loss	0.9900
3:196207396:ACCT:A	donor_loss	0.9900
3:196207499:CGATG:C	acceptor_gain	0.9900
3:196208339:T:TA	donor_gain	0.9900
3:196208558:GTC:G	acceptor_gain	0.9900
3:196208558:GTCC:G	acceptor_loss	0.9900
3:196208559:TC:T	acceptor_gain	0.9900
3:196208559:TCCTG:T	acceptor_loss	0.9900
3:196208560:CC:C	acceptor_gain	0.9900
3:196208561:CTGGG:C	acceptor_loss	0.9900
3:196208562:T:A	acceptor_loss	0.9900
3:196208566:C:CT	acceptor_gain	0.9900
3:196208567:G:T	acceptor_gain	0.9900
3:196208569:C:CT	acceptor_gain	0.9900
3:196211162:AAACT:A	donor_loss	0.9900
3:196211163:AACTC:A	donor_loss	0.9900
3:196211165:CTCAC:C	donor_loss	0.9900
3:196211167:CACG:C	donor_loss	0.9900
3:196211168:A:T	donor_loss	0.9900
3:196211253:TGGG:T	donor_gain	0.9900
3:196207401:G:A	donor_gain	0.9800

AlphaMissense

2006 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:196211190:A:C	S42R	0.983
3:196211190:A:T	S42R	0.983
3:196211192:T:G	S42R	0.983
3:196208555:A:C	F138L	0.972
3:196208555:A:T	F138L	0.972
3:196208557:A:G	F138L	0.972
3:196208510:G:C	N153K	0.964
3:196208510:G:T	N153K	0.964
3:196198845:G:C	F239L	0.961
3:196198845:G:T	F239L	0.961
3:196198847:A:G	F239L	0.961
3:196209457:G:C	F109L	0.961
3:196209457:G:T	F109L	0.961
3:196209459:A:G	F109L	0.961
3:196210659:A:C	S75R	0.951
3:196210659:A:T	S75R	0.951
3:196210661:T:G	S75R	0.951
3:196211172:G:C	F48L	0.948
3:196211172:G:T	F48L	0.948
3:196211174:A:G	F48L	0.948
3:196198823:A:G	W247R	0.944
3:196198823:A:T	W247R	0.944
3:196208498:G:C	F157L	0.942
3:196208498:G:T	F157L	0.942
3:196208500:A:G	F157L	0.942
3:196208539:A:G	W144R	0.938
3:196208539:A:T	W144R	0.938
3:196209427:G:C	F119L	0.938
3:196209427:G:T	F119L	0.938
3:196209429:A:G	F119L	0.938

dbSNP variants (sampled 300 via entrez): RS1000134160 (3:196199326 C>T), RS1000186969 (3:196199485 A>G), RS1000362653 (3:196202663 C>G,T), RS1000498594 (3:196205575 G>A,T), RS1000834793 (3:196207099 T>C), RS1000882246 (3:196207454 G>A), RS1001101198 (3:196201775 C>T), RS1001157709 (3:196213218 C>T), RS1001513654 (3:196212949 C>T), RS1001626687 (3:196208433 A>G), RS1002126870 (3:196207204 C>G), RS1002179402 (3:196206962 G>A,C), RS1002210128 (3:196202198 G>A), RS1002670528 (3:196202362 G>A), RS1002895775 (3:196204555 G>A)

Disease associations

OMIM: gene MIM:618671 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000585_5	Mean corpuscular volume	2.000000e-08
GCST000587_3	Mean corpuscular hemoglobin	4.000000e-11
GCST000918_1	HIV-1 susceptibility	7.000000e-06
GCST004004_14	Mean corpuscular volume	7.000000e-08
GCST004605_68	Mean corpuscular hemoglobin concentration	6.000000e-17
GCST004619_58	Reticulocyte fraction of red cells	7.000000e-09
GCST004630_134	Mean corpuscular hemoglobin	5.000000e-54
GCST005993_72	Mean corpuscular hemoglobin	8.000000e-38
GCST005996_59	Red blood cell count	5.000000e-11
GCST006011_102	Mean corpuscular volume	2.000000e-25
GCST012020_600	Serum metabolite levels	1.000000e-21
GCST012020_601	Serum metabolite levels	6.000000e-11
GCST012020_602	Serum metabolite levels	6.000000e-11
GCST012020_603	Serum metabolite levels	2.000000e-20
GCST012021_1	Serum metabolite levels	2.000000e-20
GCST012021_48	Serum metabolite levels	1.000000e-21
GCST012021_49	Serum metabolite levels	6.000000e-11
GCST012021_50	Serum metabolite levels	6.000000e-11
GCST90002391_10	Mean corpuscular hemoglobin concentration	2.000000e-36
GCST90002405_32	Reticulocyte count	1.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0000180	HIV-1 infection
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
triphenyl phosphate	affects expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Atrazine	increases expression	1
Cisplatin	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TY80	HAP1 ZDHHC19 (-) 1	Cancer cell line	Male
CVCL_TY81	HAP1 ZDHHC19 (-) 2	Cancer cell line	Male
CVCL_TY82	HAP1 ZDHHC19 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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