{"gene":"ZDHHC14","run_date":"2026-04-28T23:00:24","timeline":{"discoveries":[{"year":2020,"finding":"ZDHHC14 directly interacts with and palmitoylates the PDZ domain-containing MaGUK protein PSD93, which localizes to the axon initial segment (AIS). ZDHHC14-mediated palmitoylation of PSD93 controls clustering of PSD93 and Kv1 potassium channels at the AIS; shRNA knockdown of ZDHHC14 reduces palmitoylation and AIS clustering of PSD93 and Kv1, decreases outward potassium currents, and increases action potential firing in hippocampal neurons.","method":"Lentiviral shRNA knockdown in rat hippocampal neurons, co-immunoprecipitation (direct interaction), palmitoylation assay, electrophysiology, live imaging/immunofluorescence of AIS","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, shRNA KD with multiple orthogonal readouts (palmitoylation, localization, electrophysiology), replicated across substrates","pmids":["33185190"],"is_preprint":false},{"year":2014,"finding":"Inducible overexpression of ZDHHC14 reduces cell viability and increases apoptosis through the caspase-dependent apoptotic pathway; heterozygous knockout increases colony formation; overexpression inhibits tumourigenesis in a mouse xenograft model, establishing ZDHHC14 as a tumour suppressor with pro-apoptotic function.","method":"Inducible overexpression, heterozygous knockout, caspase activity assays, mouse xenograft model","journal":"The Journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function and gain-of-function with defined cellular phenotypes and in vivo validation, single lab","pmids":["24407904"],"is_preprint":false},{"year":2014,"finding":"ZDHHC14 knockdown in scirrhous gastric cancer cells decreases invasiveness, with concomitant downregulation of MMP-17 mRNA and integrins α5 and β1; forced ZDHHC14 expression promotes migration and invasion, placing ZDHHC14 upstream of MMP-17 and integrin signalling in gastric cancer invasion.","method":"siRNA knockdown, forced overexpression, invasion/migration assays (Transwell), qRT-PCR for downstream targets","journal":"Oncology reports","confidence":"Medium","confidence_rationale":"Tier 3 — KD/OE with defined downstream molecular changes, single lab, single study","pmids":["24807047"],"is_preprint":false},{"year":2025,"finding":"ZDHHC14 interacts with HSV-2 glycoprotein B (gB) and catalyses its palmitoylation at cysteine residue 8 (C8); this palmitoylation enhances gB localization to the plasma membrane and promotes efficient HSV-2 infection. The depalmitoylase APT2 acts as a negative regulator of gB palmitoylation. C8S mutation impairs membrane localization and reduces infectivity.","method":"Acyl-biotin exchange assay, co-immunoprecipitation, site-directed mutagenesis (C8S), 2-bromopalmitate treatment, HSV-2 pseudotyped particle and live virus infection assays","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 2 — acyl-biotin exchange assay, Co-IP, mutagenesis, and functional infectivity assays in single study, single lab","pmids":["40582294"],"is_preprint":false},{"year":2025,"finding":"ZDHHC14 palmitoylates transcription factor TEAD4 in injured tubular epithelial cells under inflammatory conditions; this palmitoylation regulates TEAD4 transcriptional activity (rather than expression level), driving CCL20 upregulation and subsequent Th17 cell recruitment. ZDHHC14 knockdown reduces CCL20 expression and Th17 infiltration in IgA nephropathy models.","method":"Palmitoylation assay, ZDHHC14 knockdown (siRNA), CCL20 measurement, Th17 cell infiltration quantification in mouse models and patient samples","journal":"Research (Washington, D.C.)","confidence":"Medium","confidence_rationale":"Tier 2 — KD with defined molecular (CCL20) and cellular (Th17 recruitment) phenotypes, mechanistic link to TEAD4 palmitoylation, single lab","pmids":["41112095"],"is_preprint":false},{"year":2026,"finding":"ZDHHC14 is the palmitoyltransferase catalysing ASCT2 palmitoylation at Cys39 and Cys48, promoting lysosomal degradation of ASCT2 and suppressing glutamine uptake. Glutamine deprivation activates JNK1, which phosphorylates ZDHHC14 at Thr440, triggering ZDHHC14 degradation and thereby stabilising ASCT2. ABHD17B acts as the depalmitoylase that stabilises ASCT2.","method":"Palmitoylation assay, site-directed mutagenesis (Cys39/48, Thr440), in vitro kinase assay (JNK1 phosphorylating ZDHHC14), co-immunoprecipitation, lysosomal degradation assays, in vivo tumor models","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including mutagenesis of palmitoylation sites and phosphorylation site, in vitro kinase assay, and in vivo validation in single rigorous study","pmids":["41730846"],"is_preprint":false},{"year":2025,"finding":"ZDHHC14 palmitoylates P16 (CDKN2A) at Cys72, enhancing P16 protein stability by suppressing its ubiquitination-dependent proteasomal degradation. ZDHHC14 directly interacts with P16 as confirmed by co-immunoprecipitation, and ZDHHC14 knockdown markedly reduces P16 protein levels in prostate cancer cells.","method":"Co-immunoprecipitation, site-directed mutagenesis (C72S), palmitoylation inhibitor (2-BP) and agonist (HAM) treatment, ubiquitination assay, siRNA knockdown, molecular docking","journal":"Translational andrology and urology","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP, mutagenesis, ubiquitination assay with mechanistic follow-up, single lab","pmids":["41522323"],"is_preprint":false},{"year":2018,"finding":"siRNA-mediated knockdown of ZDHHC14 inhibits trophoblast cell (BeWo and JEG-3) proliferation and invasion, and DNA hypomethylation of the ZDHHC14 gene body reduces its expression; these findings link ZDHHC14 expression (regulated by DNA methylation) to trophoblast cell function.","method":"siRNA knockdown, 5-Aza-dC demethylation treatment, proliferation and invasion assays, MassARRAY EpiTYPER methylation analysis","journal":"Pregnancy hypertension","confidence":"Low","confidence_rationale":"Tier 3 — KD phenotype with no direct palmitoylation substrate identified; co-studied with CD39, single lab","pmids":["30527120"],"is_preprint":false}],"current_model":"ZDHHC14 is a palmitoyl acyltransferase (PAT) that palmitoylates multiple substrates including PSD93 (controlling Kv1 channel clustering at the axon initial segment and neuronal excitability), ASCT2 (promoting its lysosomal degradation in a JNK1-phosphorylation-regulated axis), P16/CDKN2A (stabilising it against ubiquitin-dependent degradation), TEAD4 (regulating transcriptional activity and downstream CCL20/Th17 signalling), and HSV-2 glycoprotein B (enhancing membrane localisation and viral infectivity), while also exhibiting tumour suppressor activity through promotion of caspase-dependent apoptosis."},"narrative":{"teleology":[{"year":2014,"claim":"Establishing that ZDHHC14 functions as a tumour suppressor answered whether this palmitoyl acyltransferase had cell-autonomous growth-regulatory roles beyond enzymatic activity, revealing caspase-dependent pro-apoptotic function and anti-tumourigenic capacity in vivo.","evidence":"Inducible overexpression, heterozygous knockout, caspase assays, and mouse xenograft model in cancer cell lines","pmids":["24407904"],"confidence":"Medium","gaps":["The palmitoylation substrate(s) mediating apoptosis were not identified","Whether the tumour suppressor activity requires catalytic DHHC activity was not tested","Single lab, not independently replicated"]},{"year":2014,"claim":"Demonstrating that ZDHHC14 promotes gastric cancer cell invasion upstream of MMP-17 and integrin signalling revealed a context-dependent pro-invasive role that contrasted with the tumour-suppressive phenotype observed in other settings.","evidence":"siRNA knockdown and forced overexpression with Transwell invasion/migration assays and qRT-PCR in scirrhous gastric cancer cells","pmids":["24807047"],"confidence":"Medium","gaps":["No direct palmitoylation substrate linking ZDHHC14 to MMP-17/integrin regulation was identified","Context dependence of pro-invasive vs. tumour-suppressive roles is unresolved","Single study, single lab"]},{"year":2018,"claim":"Showing that ZDHHC14 knockdown impairs trophoblast proliferation and invasion, with expression regulated by DNA methylation, extended the functional repertoire of ZDHHC14 to placental biology, though without a defined substrate.","evidence":"siRNA knockdown, 5-Aza-dC demethylation, proliferation/invasion assays in BeWo and JEG-3 trophoblast cells","pmids":["30527120"],"confidence":"Low","gaps":["No palmitoylation substrate was identified in trophoblast cells, limiting mechanistic interpretation","Correlation between DNA methylation and expression does not establish causal regulation in vivo","Single lab, single study"]},{"year":2020,"claim":"Identifying PSD93 as a direct substrate of ZDHHC14 at the axon initial segment resolved how Kv1 channel clustering and neuronal excitability are controlled by palmitoylation, providing the first substrate-level mechanism for ZDHHC14 in neurons.","evidence":"Reciprocal co-immunoprecipitation, palmitoylation assays, shRNA knockdown with electrophysiology and AIS imaging in rat hippocampal neurons","pmids":["33185190"],"confidence":"High","gaps":["The specific palmitoylation site(s) on PSD93 were not mapped","Whether ZDHHC14 palmitoylates Kv1 channels directly or acts solely through PSD93 is unknown","In vivo validation in ZDHHC14 knockout animals is lacking"]},{"year":2025,"claim":"Discovery that ZDHHC14 palmitoylates TEAD4 to drive CCL20-dependent Th17 recruitment in injured tubular epithelial cells established ZDHHC14 as a regulator of transcription factor activity and adaptive immune signalling in kidney disease.","evidence":"Palmitoylation assay, siRNA knockdown of ZDHHC14, CCL20 measurement, and Th17 infiltration quantification in IgA nephropathy mouse models and patient samples","pmids":["41112095"],"confidence":"Medium","gaps":["The palmitoylation site on TEAD4 was not mapped by mutagenesis","Whether ZDHHC14-mediated TEAD4 palmitoylation occurs in non-renal inflammatory contexts is untested","Single lab, single study"]},{"year":2025,"claim":"Demonstrating that ZDHHC14 palmitoylates P16/CDKN2A at Cys72 to prevent ubiquitin-dependent proteasomal degradation provided a direct mechanistic link between palmitoylation and tumour suppressor protein stability.","evidence":"Co-immunoprecipitation, C72S mutagenesis, ubiquitination assays, palmitoylation inhibitor/agonist treatment, siRNA knockdown in prostate cancer cells","pmids":["41522323"],"confidence":"Medium","gaps":["The E3 ubiquitin ligase counteracted by palmitoylation was not identified","In vivo relevance for prostate cancer progression was not tested","Single lab, single study"]},{"year":2025,"claim":"Identification of HSV-2 glycoprotein B as a ZDHHC14 substrate (palmitoylated at Cys8) that enhances viral membrane localization and infectivity revealed a host–pathogen exploitation of ZDHHC14 enzymatic activity.","evidence":"Acyl-biotin exchange assay, co-immunoprecipitation, C8S mutagenesis, 2-bromopalmitate treatment, pseudotyped particle and live HSV-2 infection assays","pmids":["40582294"],"confidence":"Medium","gaps":["Whether ZDHHC14 is required vs. redundant with other DHHCs for gB palmitoylation in vivo is unclear","No in vivo infection model was used","Single lab, single study"]},{"year":2026,"claim":"Establishing that ZDHHC14 palmitoylates ASCT2 at Cys39/Cys48 to promote its lysosomal degradation, and that JNK1-mediated phosphorylation of ZDHHC14 at Thr440 triggers ZDHHC14 degradation under glutamine deprivation, revealed a nutrient-sensing feedback loop regulating amino acid transporter levels.","evidence":"Palmitoylation assay, mutagenesis of Cys39/48 and Thr440, in vitro JNK1 kinase assay, co-immunoprecipitation, lysosomal degradation assays, in vivo tumour models","pmids":["41730846"],"confidence":"High","gaps":["The E3 ligase responsible for ZDHHC14 degradation upon phosphorylation was not identified","Whether other DHHCs compensate for ZDHHC14 loss in ASCT2 regulation is unknown","The structural basis for JNK1 recognition of Thr440 is uncharacterized"]},{"year":null,"claim":"A unifying structural and regulatory model for ZDHHC14 substrate selectivity across its diverse substrates (PSD93, ASCT2, P16, TEAD4, HSV-2 gB) is lacking, and whether catalytic activity is required for its pro-apoptotic tumour suppressor function remains untested.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal structure or cryo-EM structure of ZDHHC14 exists","Catalytic-dead mutant (DHHC→DHHS) has not been tested in the apoptosis/tumour suppressor context","A ZDHHC14 knockout mouse phenotype has not been reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,3,4,5,6]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,3]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,5,6]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5]}],"complexes":[],"partners":["PSD93","ASCT2","CDKN2A","TEAD4","JNK1","ABHD17B","APT2"],"other_free_text":[]},"mechanistic_narrative":"ZDHHC14 is a DHHC-family palmitoyl acyltransferase that modifies a diverse set of substrates to control their membrane localization, protein stability, and transcriptional activity across neuronal, immune, and cancer contexts. In hippocampal neurons, ZDHHC14 palmitoylates the scaffold protein PSD93, thereby clustering PSD93 and Kv1 potassium channels at the axon initial segment to regulate neuronal excitability [PMID:33185190]. ZDHHC14 also palmitoylates the tumour suppressor P16/CDKN2A at Cys72 to shield it from ubiquitin-dependent proteasomal degradation [PMID:41522323], palmitoylates the amino acid transporter ASCT2 at Cys39/Cys48 to promote its lysosomal degradation—a process negatively regulated by JNK1-mediated phosphorylation of ZDHHC14 at Thr440 [PMID:41730846]—and palmitoylates TEAD4 to activate CCL20 transcription and Th17 cell recruitment in kidney injury [PMID:41112095]. ZDHHC14 additionally exhibits tumour suppressor activity through caspase-dependent apoptosis induction and suppression of xenograft tumourigenesis [PMID:24407904]."},"prefetch_data":{"uniprot":{"accession":"Q8IZN3","full_name":"Palmitoyltransferase ZDHHC14","aliases":["DHHC domain-containing cysteine-rich protein 14","DHHC-14","NEW1 domain-containing protein","NEW1CP","Zinc finger DHHC domain-containing protein 14"],"length_aa":488,"mass_kda":53.4,"function":"Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates. May have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and thereby regulate G protein-coupled receptor signaling (PubMed:27481942). May play a role in cell differentiation and apoptosis (PubMed:21151021, PubMed:24407904)","subcellular_location":"Endoplasmic reticulum membrane; Golgi apparatus, Golgi stack membrane","url":"https://www.uniprot.org/uniprotkb/Q8IZN3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZDHHC14","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ZDHHC14","total_profiled":1310},"omim":[{"mim_id":"619295","title":"ZDHHC PALMITOYLTRANSFERASE 14; ZDHHC14","url":"https://www.omim.org/entry/619295"},{"mim_id":"603583","title":"DISCS LARGE MAGUK SCAFFOLD PROTEIN 2; DLG2","url":"https://www.omim.org/entry/603583"},{"mim_id":"176266","title":"POTASSIUM CHANNEL, VOLTAGE-GATED, SHAKER-RELATED SUBFAMILY, MEMBER 4; KCNA4","url":"https://www.omim.org/entry/176266"},{"mim_id":"176262","title":"POTASSIUM CHANNEL, VOLTAGE-GATED, SHAKER-RELATED SUBFAMILY, MEMBER 2; KCNA2","url":"https://www.omim.org/entry/176262"},{"mim_id":"176260","title":"POTASSIUM CHANNEL, VOLTAGE-GATED, SHAKER-RELATED SUBFAMILY, MEMBER 1; KCNA1","url":"https://www.omim.org/entry/176260"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Vesicles","reliability":"Uncertain"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZDHHC14"},"hgnc":{"alias_symbol":["FLJ20984","NEW1CP"],"prev_symbol":[]},"alphafold":{"accession":"Q8IZN3","domains":[{"cath_id":"1.20.140","chopping":"60-120_199-315","consensus_level":"high","plddt":96.0454,"start":60,"end":315}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IZN3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IZN3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IZN3-F1-predicted_aligned_error_v6.png","plddt_mean":72.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZDHHC14","jax_strain_url":"https://www.jax.org/strain/search?query=ZDHHC14"},"sequence":{"accession":"Q8IZN3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IZN3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IZN3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IZN3"}},"corpus_meta":[{"pmid":"24407904","id":"PMC_24407904","title":"Identification of ZDHHC14 as a novel human tumour suppressor gene.","date":"2014","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/24407904","citation_count":52,"is_preprint":false},{"pmid":"24807047","id":"PMC_24807047","title":"Overexpression of ZDHHC14 promotes migration and invasion of scirrhous type gastric cancer.","date":"2014","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/24807047","citation_count":40,"is_preprint":false},{"pmid":"33185190","id":"PMC_33185190","title":"The palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/33185190","citation_count":36,"is_preprint":false},{"pmid":"30527120","id":"PMC_30527120","title":"Reduced methylation downregulates CD39/ENTPD1 and ZDHHC14 to suppress trophoblast cell proliferation and invasion: Implications in preeclampsia.","date":"2018","source":"Pregnancy hypertension","url":"https://pubmed.ncbi.nlm.nih.gov/30527120","citation_count":12,"is_preprint":false},{"pmid":"40582294","id":"PMC_40582294","title":"ZDHHC14 and APT2 regulate the palmitoylation of HSV-2 gB.","date":"2025","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/40582294","citation_count":1,"is_preprint":false},{"pmid":"41112095","id":"PMC_41112095","title":"ZDHHC14-Mediated TEAD4 Palmitoylation Drives Th17 Cell Recruitment in Renal Immunopathology.","date":"2025","source":"Research (Washington, D.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/41112095","citation_count":0,"is_preprint":false},{"pmid":"41730846","id":"PMC_41730846","title":"ASCT2 palmitoylation regulated by JNK1-ZDHHC14 axis orchestrates glutamine metabolism and NSCLC progression.","date":"2026","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/41730846","citation_count":0,"is_preprint":false},{"pmid":"41388152","id":"PMC_41388152","title":"ZDHHC5 and ZDHHC14 promote depression via the mediation of double-negative T cells.","date":"2025","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/41388152","citation_count":0,"is_preprint":false},{"pmid":"41962640","id":"PMC_41962640","title":"ZDHHC14 Attenuates Osteoarthritis Progression through Metabolic Pathways: Multi-omics Fusion and Functional Validation.","date":"2026","source":"Experimental gerontology","url":"https://pubmed.ncbi.nlm.nih.gov/41962640","citation_count":0,"is_preprint":false},{"pmid":"41522323","id":"PMC_41522323","title":"ZDHHC14 enhances P16 stability via palmitoylation to inhibit prostate cancer progression.","date":"2025","source":"Translational andrology and urology","url":"https://pubmed.ncbi.nlm.nih.gov/41522323","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.07.18.604152","title":"A selective S-acyltransferase inhibitor suppresses tumor growth","date":"2024-07-22","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.18.604152","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6959,"output_tokens":2323,"usd":0.027861},"stage2":{"model":"claude-opus-4-6","input_tokens":5603,"output_tokens":5433,"usd":0.24576},"total_usd":0.273621,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"ZDHHC14 directly interacts with and palmitoylates the PDZ domain-containing MaGUK protein PSD93, which localizes to the axon initial segment (AIS). ZDHHC14-mediated palmitoylation of PSD93 controls clustering of PSD93 and Kv1 potassium channels at the AIS; shRNA knockdown of ZDHHC14 reduces palmitoylation and AIS clustering of PSD93 and Kv1, decreases outward potassium currents, and increases action potential firing in hippocampal neurons.\",\n      \"method\": \"Lentiviral shRNA knockdown in rat hippocampal neurons, co-immunoprecipitation (direct interaction), palmitoylation assay, electrophysiology, live imaging/immunofluorescence of AIS\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, shRNA KD with multiple orthogonal readouts (palmitoylation, localization, electrophysiology), replicated across substrates\",\n      \"pmids\": [\"33185190\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Inducible overexpression of ZDHHC14 reduces cell viability and increases apoptosis through the caspase-dependent apoptotic pathway; heterozygous knockout increases colony formation; overexpression inhibits tumourigenesis in a mouse xenograft model, establishing ZDHHC14 as a tumour suppressor with pro-apoptotic function.\",\n      \"method\": \"Inducible overexpression, heterozygous knockout, caspase activity assays, mouse xenograft model\",\n      \"journal\": \"The Journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function and gain-of-function with defined cellular phenotypes and in vivo validation, single lab\",\n      \"pmids\": [\"24407904\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ZDHHC14 knockdown in scirrhous gastric cancer cells decreases invasiveness, with concomitant downregulation of MMP-17 mRNA and integrins α5 and β1; forced ZDHHC14 expression promotes migration and invasion, placing ZDHHC14 upstream of MMP-17 and integrin signalling in gastric cancer invasion.\",\n      \"method\": \"siRNA knockdown, forced overexpression, invasion/migration assays (Transwell), qRT-PCR for downstream targets\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — KD/OE with defined downstream molecular changes, single lab, single study\",\n      \"pmids\": [\"24807047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZDHHC14 interacts with HSV-2 glycoprotein B (gB) and catalyses its palmitoylation at cysteine residue 8 (C8); this palmitoylation enhances gB localization to the plasma membrane and promotes efficient HSV-2 infection. The depalmitoylase APT2 acts as a negative regulator of gB palmitoylation. C8S mutation impairs membrane localization and reduces infectivity.\",\n      \"method\": \"Acyl-biotin exchange assay, co-immunoprecipitation, site-directed mutagenesis (C8S), 2-bromopalmitate treatment, HSV-2 pseudotyped particle and live virus infection assays\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — acyl-biotin exchange assay, Co-IP, mutagenesis, and functional infectivity assays in single study, single lab\",\n      \"pmids\": [\"40582294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZDHHC14 palmitoylates transcription factor TEAD4 in injured tubular epithelial cells under inflammatory conditions; this palmitoylation regulates TEAD4 transcriptional activity (rather than expression level), driving CCL20 upregulation and subsequent Th17 cell recruitment. ZDHHC14 knockdown reduces CCL20 expression and Th17 infiltration in IgA nephropathy models.\",\n      \"method\": \"Palmitoylation assay, ZDHHC14 knockdown (siRNA), CCL20 measurement, Th17 cell infiltration quantification in mouse models and patient samples\",\n      \"journal\": \"Research (Washington, D.C.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with defined molecular (CCL20) and cellular (Th17 recruitment) phenotypes, mechanistic link to TEAD4 palmitoylation, single lab\",\n      \"pmids\": [\"41112095\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ZDHHC14 is the palmitoyltransferase catalysing ASCT2 palmitoylation at Cys39 and Cys48, promoting lysosomal degradation of ASCT2 and suppressing glutamine uptake. Glutamine deprivation activates JNK1, which phosphorylates ZDHHC14 at Thr440, triggering ZDHHC14 degradation and thereby stabilising ASCT2. ABHD17B acts as the depalmitoylase that stabilises ASCT2.\",\n      \"method\": \"Palmitoylation assay, site-directed mutagenesis (Cys39/48, Thr440), in vitro kinase assay (JNK1 phosphorylating ZDHHC14), co-immunoprecipitation, lysosomal degradation assays, in vivo tumor models\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including mutagenesis of palmitoylation sites and phosphorylation site, in vitro kinase assay, and in vivo validation in single rigorous study\",\n      \"pmids\": [\"41730846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZDHHC14 palmitoylates P16 (CDKN2A) at Cys72, enhancing P16 protein stability by suppressing its ubiquitination-dependent proteasomal degradation. ZDHHC14 directly interacts with P16 as confirmed by co-immunoprecipitation, and ZDHHC14 knockdown markedly reduces P16 protein levels in prostate cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis (C72S), palmitoylation inhibitor (2-BP) and agonist (HAM) treatment, ubiquitination assay, siRNA knockdown, molecular docking\",\n      \"journal\": \"Translational andrology and urology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP, mutagenesis, ubiquitination assay with mechanistic follow-up, single lab\",\n      \"pmids\": [\"41522323\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"siRNA-mediated knockdown of ZDHHC14 inhibits trophoblast cell (BeWo and JEG-3) proliferation and invasion, and DNA hypomethylation of the ZDHHC14 gene body reduces its expression; these findings link ZDHHC14 expression (regulated by DNA methylation) to trophoblast cell function.\",\n      \"method\": \"siRNA knockdown, 5-Aza-dC demethylation treatment, proliferation and invasion assays, MassARRAY EpiTYPER methylation analysis\",\n      \"journal\": \"Pregnancy hypertension\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — KD phenotype with no direct palmitoylation substrate identified; co-studied with CD39, single lab\",\n      \"pmids\": [\"30527120\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZDHHC14 is a palmitoyl acyltransferase (PAT) that palmitoylates multiple substrates including PSD93 (controlling Kv1 channel clustering at the axon initial segment and neuronal excitability), ASCT2 (promoting its lysosomal degradation in a JNK1-phosphorylation-regulated axis), P16/CDKN2A (stabilising it against ubiquitin-dependent degradation), TEAD4 (regulating transcriptional activity and downstream CCL20/Th17 signalling), and HSV-2 glycoprotein B (enhancing membrane localisation and viral infectivity), while also exhibiting tumour suppressor activity through promotion of caspase-dependent apoptosis.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ZDHHC14 is a DHHC-family palmitoyl acyltransferase that modifies a diverse set of substrates to control their membrane localization, protein stability, and transcriptional activity across neuronal, immune, and cancer contexts. In hippocampal neurons, ZDHHC14 palmitoylates the scaffold protein PSD93, thereby clustering PSD93 and Kv1 potassium channels at the axon initial segment to regulate neuronal excitability [PMID:33185190]. ZDHHC14 also palmitoylates the tumour suppressor P16/CDKN2A at Cys72 to shield it from ubiquitin-dependent proteasomal degradation [PMID:41522323], palmitoylates the amino acid transporter ASCT2 at Cys39/Cys48 to promote its lysosomal degradation—a process negatively regulated by JNK1-mediated phosphorylation of ZDHHC14 at Thr440 [PMID:41730846]—and palmitoylates TEAD4 to activate CCL20 transcription and Th17 cell recruitment in kidney injury [PMID:41112095]. ZDHHC14 additionally exhibits tumour suppressor activity through caspase-dependent apoptosis induction and suppression of xenograft tumourigenesis [PMID:24407904].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that ZDHHC14 functions as a tumour suppressor answered whether this palmitoyl acyltransferase had cell-autonomous growth-regulatory roles beyond enzymatic activity, revealing caspase-dependent pro-apoptotic function and anti-tumourigenic capacity in vivo.\",\n      \"evidence\": \"Inducible overexpression, heterozygous knockout, caspase assays, and mouse xenograft model in cancer cell lines\",\n      \"pmids\": [\"24407904\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The palmitoylation substrate(s) mediating apoptosis were not identified\",\n        \"Whether the tumour suppressor activity requires catalytic DHHC activity was not tested\",\n        \"Single lab, not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that ZDHHC14 promotes gastric cancer cell invasion upstream of MMP-17 and integrin signalling revealed a context-dependent pro-invasive role that contrasted with the tumour-suppressive phenotype observed in other settings.\",\n      \"evidence\": \"siRNA knockdown and forced overexpression with Transwell invasion/migration assays and qRT-PCR in scirrhous gastric cancer cells\",\n      \"pmids\": [\"24807047\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct palmitoylation substrate linking ZDHHC14 to MMP-17/integrin regulation was identified\",\n        \"Context dependence of pro-invasive vs. tumour-suppressive roles is unresolved\",\n        \"Single study, single lab\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showing that ZDHHC14 knockdown impairs trophoblast proliferation and invasion, with expression regulated by DNA methylation, extended the functional repertoire of ZDHHC14 to placental biology, though without a defined substrate.\",\n      \"evidence\": \"siRNA knockdown, 5-Aza-dC demethylation, proliferation/invasion assays in BeWo and JEG-3 trophoblast cells\",\n      \"pmids\": [\"30527120\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No palmitoylation substrate was identified in trophoblast cells, limiting mechanistic interpretation\",\n        \"Correlation between DNA methylation and expression does not establish causal regulation in vivo\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying PSD93 as a direct substrate of ZDHHC14 at the axon initial segment resolved how Kv1 channel clustering and neuronal excitability are controlled by palmitoylation, providing the first substrate-level mechanism for ZDHHC14 in neurons.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, palmitoylation assays, shRNA knockdown with electrophysiology and AIS imaging in rat hippocampal neurons\",\n      \"pmids\": [\"33185190\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific palmitoylation site(s) on PSD93 were not mapped\",\n        \"Whether ZDHHC14 palmitoylates Kv1 channels directly or acts solely through PSD93 is unknown\",\n        \"In vivo validation in ZDHHC14 knockout animals is lacking\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Discovery that ZDHHC14 palmitoylates TEAD4 to drive CCL20-dependent Th17 recruitment in injured tubular epithelial cells established ZDHHC14 as a regulator of transcription factor activity and adaptive immune signalling in kidney disease.\",\n      \"evidence\": \"Palmitoylation assay, siRNA knockdown of ZDHHC14, CCL20 measurement, and Th17 infiltration quantification in IgA nephropathy mouse models and patient samples\",\n      \"pmids\": [\"41112095\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The palmitoylation site on TEAD4 was not mapped by mutagenesis\",\n        \"Whether ZDHHC14-mediated TEAD4 palmitoylation occurs in non-renal inflammatory contexts is untested\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrating that ZDHHC14 palmitoylates P16/CDKN2A at Cys72 to prevent ubiquitin-dependent proteasomal degradation provided a direct mechanistic link between palmitoylation and tumour suppressor protein stability.\",\n      \"evidence\": \"Co-immunoprecipitation, C72S mutagenesis, ubiquitination assays, palmitoylation inhibitor/agonist treatment, siRNA knockdown in prostate cancer cells\",\n      \"pmids\": [\"41522323\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The E3 ubiquitin ligase counteracted by palmitoylation was not identified\",\n        \"In vivo relevance for prostate cancer progression was not tested\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of HSV-2 glycoprotein B as a ZDHHC14 substrate (palmitoylated at Cys8) that enhances viral membrane localization and infectivity revealed a host–pathogen exploitation of ZDHHC14 enzymatic activity.\",\n      \"evidence\": \"Acyl-biotin exchange assay, co-immunoprecipitation, C8S mutagenesis, 2-bromopalmitate treatment, pseudotyped particle and live HSV-2 infection assays\",\n      \"pmids\": [\"40582294\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether ZDHHC14 is required vs. redundant with other DHHCs for gB palmitoylation in vivo is unclear\",\n        \"No in vivo infection model was used\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Establishing that ZDHHC14 palmitoylates ASCT2 at Cys39/Cys48 to promote its lysosomal degradation, and that JNK1-mediated phosphorylation of ZDHHC14 at Thr440 triggers ZDHHC14 degradation under glutamine deprivation, revealed a nutrient-sensing feedback loop regulating amino acid transporter levels.\",\n      \"evidence\": \"Palmitoylation assay, mutagenesis of Cys39/48 and Thr440, in vitro JNK1 kinase assay, co-immunoprecipitation, lysosomal degradation assays, in vivo tumour models\",\n      \"pmids\": [\"41730846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The E3 ligase responsible for ZDHHC14 degradation upon phosphorylation was not identified\",\n        \"Whether other DHHCs compensate for ZDHHC14 loss in ASCT2 regulation is unknown\",\n        \"The structural basis for JNK1 recognition of Thr440 is uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and regulatory model for ZDHHC14 substrate selectivity across its diverse substrates (PSD93, ASCT2, P16, TEAD4, HSV-2 gB) is lacking, and whether catalytic activity is required for its pro-apoptotic tumour suppressor function remains untested.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal structure or cryo-EM structure of ZDHHC14 exists\",\n        \"Catalytic-dead mutant (DHHC→DHHS) has not been tested in the apoptosis/tumour suppressor context\",\n        \"A ZDHHC14 knockout mouse phenotype has not been reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 3, 4, 5, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005357801\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 5, 6]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PSD93\",\n      \"ASCT2\",\n      \"CDKN2A\",\n      \"TEAD4\",\n      \"JNK1\",\n      \"ABHD17B\",\n      \"APT2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway entry. Let me correct `\"GO:0005357801\"` — that's not a valid Reactome ID. The correct one for Programmed Cell Death is `R-HSA-5357801`.\n\n```json\n{\n  \"mechanistic_narrative\": \"ZDHHC14 is a DHHC-family palmitoyl acyltransferase that modifies a diverse set of substrates to control their membrane localization, protein stability, and transcriptional activity across neuronal, immune, and cancer contexts. In hippocampal neurons, ZDHHC14 palmitoylates the scaffold protein PSD93, thereby clustering PSD93 and Kv1 potassium channels at the axon initial segment to regulate neuronal excitability [PMID:33185190]. ZDHHC14 also palmitoylates the tumour suppressor P16/CDKN2A at Cys72 to shield it from ubiquitin-dependent proteasomal degradation [PMID:41522323], palmitoylates the amino acid transporter ASCT2 at Cys39/Cys48 to promote its lysosomal degradation—a process negatively regulated by JNK1-mediated phosphorylation of ZDHHC14 at Thr440 [PMID:41730846]—and palmitoylates TEAD4 to activate CCL20 transcription and Th17 cell recruitment in kidney injury [PMID:41112095]. ZDHHC14 additionally exhibits tumour suppressor activity through caspase-dependent apoptosis induction and suppression of xenograft tumourigenesis [PMID:24407904].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that ZDHHC14 functions as a tumour suppressor answered whether this palmitoyl acyltransferase had cell-autonomous growth-regulatory roles beyond enzymatic activity, revealing caspase-dependent pro-apoptotic function and anti-tumourigenic capacity in vivo.\",\n      \"evidence\": \"Inducible overexpression, heterozygous knockout, caspase assays, and mouse xenograft model in cancer cell lines\",\n      \"pmids\": [\"24407904\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The palmitoylation substrate(s) mediating apoptosis were not identified\",\n        \"Whether the tumour suppressor activity requires catalytic DHHC activity was not tested\",\n        \"Single lab, not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that ZDHHC14 promotes gastric cancer cell invasion upstream of MMP-17 and integrin signalling revealed a context-dependent pro-invasive role that contrasted with the tumour-suppressive phenotype observed in other settings.\",\n      \"evidence\": \"siRNA knockdown and forced overexpression with Transwell invasion/migration assays and qRT-PCR in scirrhous gastric cancer cells\",\n      \"pmids\": [\"24807047\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct palmitoylation substrate linking ZDHHC14 to MMP-17/integrin regulation was identified\",\n        \"Context dependence of pro-invasive vs. tumour-suppressive roles is unresolved\",\n        \"Single study, single lab\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showing that ZDHHC14 knockdown impairs trophoblast proliferation and invasion, with expression regulated by DNA methylation, extended the functional repertoire of ZDHHC14 to placental biology, though without a defined substrate.\",\n      \"evidence\": \"siRNA knockdown, 5-Aza-dC demethylation, proliferation/invasion assays in BeWo and JEG-3 trophoblast cells\",\n      \"pmids\": [\"30527120\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No palmitoylation substrate was identified in trophoblast cells, limiting mechanistic interpretation\",\n        \"Correlation between DNA methylation and expression does not establish causal regulation in vivo\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying PSD93 as a direct substrate of ZDHHC14 at the axon initial segment resolved how Kv1 channel clustering and neuronal excitability are controlled by palmitoylation, providing the first substrate-level mechanism for ZDHHC14 in neurons.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, palmitoylation assays, shRNA knockdown with electrophysiology and AIS imaging in rat hippocampal neurons\",\n      \"pmids\": [\"33185190\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific palmitoylation site(s) on PSD93 were not mapped\",\n        \"Whether ZDHHC14 palmitoylates Kv1 channels directly or acts solely through PSD93 is unknown\",\n        \"In vivo validation in ZDHHC14 knockout animals is lacking\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Discovery that ZDHHC14 palmitoylates TEAD4 to drive CCL20-dependent Th17 recruitment in injured tubular epithelial cells established ZDHHC14 as a regulator of transcription factor activity and adaptive immune signalling in kidney disease.\",\n      \"evidence\": \"Palmitoylation assay, siRNA knockdown of ZDHHC14, CCL20 measurement, and Th17 infiltration quantification in IgA nephropathy mouse models and patient samples\",\n      \"pmids\": [\"41112095\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The palmitoylation site on TEAD4 was not mapped by mutagenesis\",\n        \"Whether ZDHHC14-mediated TEAD4 palmitoylation occurs in non-renal inflammatory contexts is untested\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrating that ZDHHC14 palmitoylates P16/CDKN2A at Cys72 to prevent ubiquitin-dependent proteasomal degradation provided a direct mechanistic link between palmitoylation and tumour suppressor protein stability.\",\n      \"evidence\": \"Co-immunoprecipitation, C72S mutagenesis, ubiquitination assays, palmitoylation inhibitor/agonist treatment, siRNA knockdown in prostate cancer cells\",\n      \"pmids\": [\"41522323\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The E3 ubiquitin ligase counteracted by palmitoylation was not identified\",\n        \"In vivo relevance for prostate cancer progression was not tested\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of HSV-2 glycoprotein B as a ZDHHC14 substrate (palmitoylated at Cys8) that enhances viral membrane localization and infectivity revealed a host–pathogen exploitation of ZDHHC14 enzymatic activity.\",\n      \"evidence\": \"Acyl-biotin exchange assay, co-immunoprecipitation, C8S mutagenesis, 2-bromopalmitate treatment, pseudotyped particle and live HSV-2 infection assays\",\n      \"pmids\": [\"40582294\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether ZDHHC14 is required vs. redundant with other DHHCs for gB palmitoylation in vivo is unclear\",\n        \"No in vivo infection model was used\",\n        \"Single lab, single study\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Establishing that ZDHHC14 palmitoylates ASCT2 at Cys39/Cys48 to promote its lysosomal degradation, and that JNK1-mediated phosphorylation of ZDHHC14 at Thr440 triggers ZDHHC14 degradation under glutamine deprivation, revealed a nutrient-sensing feedback loop regulating amino acid transporter levels.\",\n      \"evidence\": \"Palmitoylation assay, mutagenesis of Cys39/48 and Thr440, in vitro JNK1 kinase assay, co-immunoprecipitation, lysosomal degradation assays, in vivo tumour models\",\n      \"pmids\": [\"41730846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The E3 ligase responsible for ZDHHC14 degradation upon phosphorylation was not identified\",\n        \"Whether other DHHCs compensate for ZDHHC14 loss in ASCT2 regulation is unknown\",\n        \"The structural basis for JNK1 recognition of Thr440 is uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and regulatory model for ZDHHC14 substrate selectivity across its diverse substrates (PSD93, ASCT2, P16, TEAD4, HSV-2 gB) is lacking, and whether catalytic activity is required for its pro-apoptotic tumour suppressor function remains untested.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal structure or cryo-EM structure of ZDHHC14 exists\",\n        \"Catalytic-dead mutant (DHHC→DHHS) has not been tested in the apoptosis/tumour suppressor context\",\n        \"A ZDHHC14 knockout mouse phenotype has not been reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 3, 4, 5, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 5, 6]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PSD93\",\n      \"ASCT2\",\n      \"CDKN2A\",\n      \"TEAD4\",\n      \"JNK1\",\n      \"ABHD17B\",\n      \"APT2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}