ZDHHC12

Summary

ZDHHC12 (zDHHC palmitoyltransferase 12, HGNC:19159) is a protein-coding gene on chromosome 9q34.11, encoding Palmitoyltransferase ZDHHC12 (Q96GR4). Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates.

Enables protein-cysteine S-palmitoyltransferase activity. Involved in gephyrin clustering involved in postsynaptic density assembly; negative regulation of NLRP3 inflammasome complex assembly; and protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum. Is active in dendritic spine.

Source: NCBI Gene 84885 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_032799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19159
Approved symbol	ZDHHC12
Name	zDHHC palmitoyltransferase 12
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	ZNF400, FLJ14524
Ensembl gene	ENSG00000160446
Ensembl biotype	protein_coding
OMIM	621348
Entrez	84885

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000372663, ENST00000372667, ENST00000406904, ENST00000452105, ENST00000467312, ENST00000855472, ENST00000855473, ENST00000855474, ENST00000855475, ENST00000855476, ENST00000935785, ENST00000935786, ENST00000935787, ENST00000958715

RefSeq mRNA: 5 — MANE Select: NM_032799 NM_001318015, NM_001318016, NM_001318020, NM_001318023, NM_032799

CCDS: CCDS6909

Canonical transcript exons

ENST00000372663 — 5 exons

Exon	Start	End
ENSE00001052432	128722438	128722574
ENSE00001562692	128723994	128724127
ENSE00001818920	128720873	128721502
ENSE00003624120	128722009	128722086
ENSE00003624350	128721651	128721817

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 96.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0157 / max 208.2473, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102699	28.0157	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.36	gold quality
lower esophagus mucosa	UBERON:0035834	94.26	gold quality
esophagus mucosa	UBERON:0002469	93.05	gold quality
body of pancreas	UBERON:0001150	92.86	gold quality
body of stomach	UBERON:0001161	92.04	gold quality
minor salivary gland	UBERON:0001830	91.21	gold quality
transverse colon	UBERON:0001157	91.16	gold quality
granulocyte	CL:0000094	91.13	gold quality
right lobe of liver	UBERON:0001114	90.83	gold quality
skin of abdomen	UBERON:0001416	90.00	gold quality
skin of leg	UBERON:0001511	89.95	gold quality
mouth mucosa	UBERON:0003729	89.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.37	gold quality
leukocyte	CL:0000738	88.72	gold quality
monocyte	CL:0000576	88.54	gold quality
saliva-secreting gland	UBERON:0001044	88.51	gold quality
esophagus	UBERON:0001043	88.33	gold quality
metanephros cortex	UBERON:0010533	88.31	gold quality
right adrenal gland	UBERON:0001233	88.12	gold quality
stomach	UBERON:0000945	87.58	gold quality
zone of skin	UBERON:0000014	87.41	gold quality
gingival epithelium	UBERON:0001949	87.37	silver quality
right adrenal gland cortex	UBERON:0035827	87.35	gold quality
small intestine	UBERON:0002108	87.34	gold quality
left adrenal gland	UBERON:0001234	86.88	gold quality
spleen	UBERON:0002106	86.68	gold quality
left adrenal gland cortex	UBERON:0035825	86.59	gold quality
upper lobe of left lung	UBERON:0008952	86.09	gold quality
blood	UBERON:0000178	85.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting ZDHHC12, 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-3120-5P	100.00	65.56	965
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	zdhhc12b	ENSDARG00000052787
danio_rerio	zdhhc12a	ENSDARG00000076632
mus_musculus	Zdhhc12	ENSMUSG00000015335
rattus_norvegicus	Zdhhc12	ENSRNOG00000015791
drosophila_melanogaster	Dnz1	FBGN0027453
caenorhabditis_elegans	dhhc-7	WBGENE00007637
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), 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 ZDHHC12 — Q96GR4 (reviewed: Q96GR4)

Alternative names: DHHC domain-containing cysteine-rich protein 12, Zinc finger DHHC domain-containing protein 12, Zinc finger protein 400

All UniProt accessions (4): Q96GR4, Q5T266, Q5T269, X6RBN4

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates. Has a palmitoyltransferase activity toward gephyrin/GPHN, regulating its clustering at synapses and its function in gamma-aminobutyric acid receptor clustering. Thereby, indirectly regulates GABAergic synaptic transmission. Negatively regulates NLRP3-driven inflammation. Catalyzes NLRP3 palmitoylation, leading to its degradation via the chaperone-mediated autophagy (CMA) process.

Subcellular location. Golgi apparatus membrane. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed.

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

Similarity. Belongs to the DHHC palmitoyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96GR4-1	1	yes
Q96GR4-2	2
Q96GR4-3	3

RefSeq proteins (5): NP_001304944, NP_001304945, NP_001304949, NP_001304952, NP_116188* (*=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 (17 total): topological domain 5, transmembrane region 4, splice variant 2, sequence variant 2, chain 1, domain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GR4-F1	88.17	0.73

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): 127 (s-palmitoyl cysteine intermediate)

Mutagenesis-validated functional residues (1):

Position	Phenotype
127	loss of protein-cysteine s-palmitoyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_INFLAMMATORY_RESPONSE, GOBP_SYNAPSE_ASSEMBLY, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PEPTIDYL_CYSTEINE_MODIFICATION, GOBP_CELL_CELL_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, RICKMAN_METASTASIS_DN, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (10): protein targeting to membrane (GO:0006612), peptidyl-L-cysteine S-palmitoylation (GO:0018230), positive regulation of synaptic transmission, GABAergic (GO:0032230), gephyrin clustering involved in postsynaptic density assembly (GO:0097116), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226), protein catabolic process (GO:0030163), synaptic transmission, GABAergic (GO:0051932), chaperone-mediated autophagy (GO:0061684), protein targeting to lysosome involved in chaperone-mediated autophagy (GO:0061740), gamma-aminobutyric acid receptor clustering (GO:0097112)

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 (8): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), dendritic spine (GO:0043197), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor binding	2
protein-folding chaperone binding	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	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
regulation of synaptic transmission, GABAergic	1
positive regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
protein localization to synapse	1
postsynaptic density assembly	1
negative regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
negative regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
macromolecule catabolic process	1
protein metabolic process	1
chemical synaptic transmission	1
autophagy	1
protein catabolic process	1
protein carrier activity	1
protein targeting to lysosome	1
chaperone-mediated autophagy	1
protein targeting to vacuole involved in autophagy	1
postsynaptic membrane organization	1
neurotransmitter-gated ion channel clustering	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
palmitoyltransferase activity	1
protein-cysteine S-acyltransferase activity	1
binding	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

Protein interactions and networks

STRING

448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC12	ZDHHC22	Q8N966	645
ZDHHC12	ZDHHC24	Q6UX98	525
ZDHHC12	OR5L1	Q8NGL2	455
ZDHHC12	GPHN	Q9NQX3	411
ZDHHC12	PPT2	Q9UMR5	399
ZDHHC12	ZDHHC13	Q8IUH4	395
ZDHHC12	PPT1	P50897	382
ZDHHC12	ANKRD9	Q96BM1	376
ZDHHC12	ZFP28	Q8NHY6	355
ZDHHC12	ABHD17A	Q96GS6	327
ZDHHC12	TMEM179	Q6ZVK1	317
ZDHHC12	MROH6	A6NGR9	316
ZDHHC12	SSC4D	Q8WTU2	312
ZDHHC12	ZMAT5	Q9UDW3	305
ZDHHC12	ZDHHC4	Q9NPG8	305

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ZDHHC12	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
	ZDHHC12	psi-mi:“MI:0915”(physical association)	0.370
ZDHHC12	RXRB	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	FAAH	psi-mi:“MI:0914”(association)	0.350

BioGRID (126): LEMD2 (Affinity Capture-MS), SLC41A3 (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), GUCY1B3 (Affinity Capture-MS), SYVN1 (Affinity Capture-MS), PIGO (Affinity Capture-MS), ELOVL4 (Affinity Capture-MS), TSPAN15 (Affinity Capture-MS), PKMYT1 (Affinity Capture-MS), ABCC10 (Affinity Capture-MS), ABCD4 (Affinity Capture-MS), PPP1R15B (Affinity Capture-MS), SLC12A4 (Affinity Capture-MS)

ESM2 similar proteins: A0PK84, A3KN25, A6NE52, A6NGB7, B0S5D5, B1H1H3, D3ZVB0, E7F021, G3MZC5, O70491, O75064, P59267, Q0V8E7, Q0VD38, Q1XHX8, Q2TGI5, Q2TGI8, Q2VPB7, Q32LM8, Q3TAP4, Q3U1Y4, Q4QR83, Q562E7, Q58DT3, Q5FVR1, Q5R7B4, Q5TM67, Q6DGF5, Q6IR37, Q6UX98, Q6ZS72, Q767L9, Q810M5, Q86VD9, Q86YV9, Q8BSD4, Q8IXM6, Q8K0R6, Q8N966, Q8NFK1

Diamond homologs: B0S5D5, E7F021, Q6DGF5, Q8VC90, Q96GR4, A2CEX1, A2VEY9, A5WVX9, B8A4F0, C8VCL4, E1BLT8, E7FBS9, E7FH11, E9PTT0, E9QCD3, F1Q7H8, F1QAM1, F1QHM7, F1QX91, F1R013, J9VJ99, O60069, O80685, P0CS66, P0CS67, P0CS68, P0CS69, P39010, P59267, Q04629, Q09701, Q0WQK2, Q12013, Q2TGI5, Q2TGJ4, Q2THW0, Q2THW7, Q2THW8, Q2THW9, Q2THX0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

840 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128721410:A:T	acceptor_gain	1.0000
9:128721646:CCCA:C	donor_loss	1.0000
9:128721648:CAC:C	donor_loss	1.0000
9:128721649:ACCA:A	donor_loss	1.0000
9:128721650:C:A	donor_loss	1.0000
9:128721813:GGCTG:G	acceptor_gain	1.0000
9:128721814:GCTG:G	acceptor_loss	1.0000
9:128721815:CTG:C	acceptor_gain	1.0000
9:128721816:TG:T	acceptor_gain	1.0000
9:128721816:TGCTG:T	acceptor_loss	1.0000
9:128721817:GC:G	acceptor_loss	1.0000
9:128721818:C:CA	acceptor_loss	1.0000
9:128721818:C:CC	acceptor_gain	1.0000
9:128721819:T:G	acceptor_loss	1.0000
9:128721820:G:C	acceptor_gain	1.0000
9:128721826:A:AC	acceptor_gain	1.0000
9:128721826:A:C	acceptor_gain	1.0000
9:128722007:A:AC	donor_gain	1.0000
9:128722008:C:CC	donor_gain	1.0000
9:128722082:TCCTC:T	acceptor_gain	1.0000
9:128722083:CCTCC:C	acceptor_gain	1.0000
9:128722084:CTC:C	acceptor_gain	1.0000
9:128722085:TC:T	acceptor_gain	1.0000
9:128722086:CC:C	acceptor_gain	1.0000
9:128722087:C:CC	acceptor_gain	1.0000
9:128722087:CT:C	acceptor_loss	1.0000
9:128722092:A:AC	acceptor_gain	1.0000
9:128722433:GTTAC:G	donor_loss	1.0000
9:128722434:TTACC:T	donor_loss	1.0000
9:128722435:TA:T	donor_loss	1.0000

AlphaMissense

1686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128721807:C:A	R109M	0.999
9:128721356:G:A	T210I	0.998
9:128721707:A:C	F142L	0.998
9:128721707:A:T	F142L	0.998
9:128721709:A:G	F142L	0.998
9:128721762:T:A	D124V	0.998
9:128721774:A:T	V120D	0.998
9:128721807:C:G	R109T	0.998
9:128721708:A:C	F142C	0.997
9:128721708:A:G	F142S	0.997
9:128721719:G:C	N138K	0.997
9:128721719:G:T	N138K	0.997
9:128721729:C:A	G135V	0.997
9:128721762:T:G	D124A	0.997
9:128721806:C:A	R109S	0.997
9:128721806:C:G	R109S	0.997
9:128721292:G:C	F231L	0.996
9:128721292:G:T	F231L	0.996
9:128721294:A:G	F231L	0.996
9:128721729:C:T	G135E	0.996
9:128721734:A:C	C133W	0.996
9:128721754:A:G	C127R	0.996
9:128721755:G:C	H126Q	0.996
9:128721755:G:T	H126Q	0.996
9:128721758:G:C	H125Q	0.996
9:128721758:G:T	H125Q	0.996
9:128721760:G:C	H125D	0.996
9:128721761:G:C	D124E	0.996
9:128721761:G:T	D124E	0.996
9:128721797:G:C	H112Q	0.996

dbSNP variants (sampled 300 via entrez): RS1001029491 (9:128723737 C>T), RS1002020588 (9:128720804 T>G), RS1002170123 (9:128722974 G>A), RS1002304604 (9:128722621 A>T), RS1003023282 (9:128721902 G>A,T), RS1004768884 (9:128723437 T>C,G), RS1004988275 (9:128724399 T>C,G), RS1005546908 (9:128725948 G>A,T), RS1005556180 (9:128720988 C>A,T), RS1005640333 (9:128725651 G>A), RS1006107588 (9:128725398 T>C), RS1006645543 (9:128725555 G>A), RS1007871825 (9:128722477 G>A), RS1007988072 (9:128722218 G>C), RS1008452208 (9:128723857 A>C,G)

Disease associations

OMIM: gene MIM:621348 | 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
GCST001959_7	Eating disorders (purging via substances)	5.000000e-06
GCST002115_14	Axial length	6.000000e-06
GCST005951_65	Body mass index	5.000000e-09
GCST009720_47	Asthma	2.000000e-08
GCST010042_46	Asthma	1.000000e-10
GCST010043_1	Asthma	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression	3
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
diallyl trisulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Tunicamycin	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TY65	HAP1 ZDHHC12 (-) 1	Cancer cell line	Male
CVCL_TY66	HAP1 ZDHHC12 (-) 2	Cancer cell line	Male
CVCL_TY67	HAP1 ZDHHC12 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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