ZDHHC20

Summary

ZDHHC20 (zDHHC palmitoyltransferase 20, HGNC:20749) is a protein-coding gene on chromosome 13q12.11, encoding Palmitoyltransferase ZDHHC20 (Q5W0Z9). Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates.

Enables protein-cysteine S-palmitoyltransferase activity and zinc ion binding activity. Involved in peptidyl-L-cysteine S-palmitoylation and positive regulation by host of viral process. Located in Golgi membrane and plasma membrane.

Source: NCBI Gene 253832 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• Druggable target: yes
• MANE Select transcript: NM_001330059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20749
Approved symbol	ZDHHC20
Name	zDHHC palmitoyltransferase 20
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25952, DHHC20
Ensembl gene	ENSG00000180776
Ensembl biotype	protein_coding
OMIM	617972
Entrez	253832

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000320220, ENST00000382466, ENST00000400590, ENST00000415724, ENST00000464055, ENST00000477811, ENST00000484277, ENST00000494731, ENST00000542645, ENST00000626464, ENST00000700725, ENST00000926899, ENST00000942990

RefSeq mRNA: 3 — MANE Select: NM_001330059 NM_001286638, NM_001330059, NM_153251

CCDS: CCDS45017, CCDS73551, CCDS81758

Canonical transcript exons

ENST00000400590 — 13 exons

Exon	Start	End
ENSE00001260822	21425652	21425678
ENSE00001492257	21459054	21459303
ENSE00003469674	21382920	21383009
ENSE00003474328	21413652	21413772
ENSE00003479993	21391722	21391854
ENSE00003505307	21421061	21421164
ENSE00003532337	21401653	21401685
ENSE00003539199	21387508	21387634
ENSE00003674660	21402797	21402866
ENSE00003980657	21381434	21381549
ENSE00003980661	21372571	21376655
ENSE00003980662	21400373	21400493
ENSE00003980663	21378661	21378738

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8925 / max 404.2117, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136390	17.8498	1799
136389	1.0427	677

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.43	gold quality
inferior vagus X ganglion	UBERON:0005363	99.04	gold quality
corpus callosum	UBERON:0002336	98.83	gold quality
subthalamic nucleus	UBERON:0001906	98.69	gold quality
oral cavity	UBERON:0000167	98.68	gold quality
pons	UBERON:0000988	98.64	gold quality
ileal mucosa	UBERON:0000331	98.61	gold quality
nasal cavity epithelium	UBERON:0005384	98.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.52	gold quality
medulla oblongata	UBERON:0001896	98.18	gold quality
substantia nigra pars compacta	UBERON:0001965	98.09	gold quality
pylorus	UBERON:0001166	98.08	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.92	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.90	gold quality
superior vestibular nucleus	UBERON:0007227	97.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.85	gold quality
penis	UBERON:0000989	97.82	gold quality
pharyngeal mucosa	UBERON:0000355	97.77	gold quality
jejunal mucosa	UBERON:0000399	97.77	gold quality
mammalian vulva	UBERON:0000997	97.64	gold quality
ventral tegmental area	UBERON:0002691	97.46	gold quality
superficial temporal artery	UBERON:0001614	97.41	gold quality
epithelium of nasopharynx	UBERON:0001951	97.38	gold quality
upper leg skin	UBERON:0004262	97.36	gold quality
spinal cord	UBERON:0002240	97.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.18	gold quality
monocyte	CL:0000576	97.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.99	gold quality
lateral globus pallidus	UBERON:0002476	96.97	gold quality
esophagus squamous epithelium	UBERON:0006920	96.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

194 targeting ZDHHC20, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 9)

• DHHC20 is a human N-terminal-myristoyl-directed palmitoyl acyltransferase involved in cellular transformation, that may play a role in cancer. (PMID:20334580)
• Targeting of a peripheral modulator of EGFR signaling, DHHC20, causes a loss of signal regulation and susceptibility to EGFR inhibitor-induced cell death. (PMID:27153536)
• crystal structure determined; active site resides at the membrane-cytosol interface; acyl chain binds in a cavity formed by the transmembrane domain; propose a mechanism for acyl chain-length selectivity in DHHC enzymes on the basis of cavity mutants with preferences for shorter and longer acyl chains (PMID:29326245)
• DHHC20 Palmitoyl-Transferase Reshapes the Membrane to Foster Catalysis. (PMID:31858978)
• Regulation of EGFR signalling by palmitoylation and its role in tumorigenesis. (PMID:34610265)
• S-acylation by ZDHHC20 targets ORAI1 channels to lipid rafts for efficient Ca(2+) signaling by Jurkat T cell receptors at the immune synapse. (PMID:34913437)
• Bivalent recognition of fatty acyl-CoA by a human integral membrane palmitoyltransferase. (PMID:35140179)
• Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis. (PMID:38733589)
• ZDHHC20-mediated S-palmitoylation of YTHDF3 stabilizes MYC mRNA to promote pancreatic cancer progression. (PMID:38821916)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	zdhhc20a	ENSDARG00000055066
danio_rerio	zdhhc20b	ENSDARG00000058178
mus_musculus	Zdhhc20	ENSMUSG00000021969
rattus_norvegicus	Zdhhc20	ENSRNOG00000011024
drosophila_melanogaster	Dnz1	FBGN0027453
drosophila_melanogaster	CG1407	FBGN0033474
drosophila_melanogaster	CG17287	FBGN0034202
caenorhabditis_elegans	dhhc-7	WBGENE00007637
caenorhabditis_elegans	dhhc-12	WBGENE00010323
caenorhabditis_elegans	dhhc-2	WBGENE00012948
caenorhabditis_elegans		WBGENE00014075
caenorhabditis_elegans		WBGENE00016620
caenorhabditis_elegans		WBGENE00020066

Paralogs (17): ZDHHC6 (ENSG00000023041), ZDHHC15 (ENSG00000102383), ZDHHC2 (ENSG00000104219), ZDHHC4 (ENSG00000136247), ZDHHC7 (ENSG00000153786), ZDHHC1 (ENSG00000159714), ZDHHC12 (ENSG00000160446), ZDHHC3 (ENSG00000163812), ZDHHC19 (ENSG00000163958), ZDHHC14 (ENSG00000175048), ZDHHC21 (ENSG00000175893), ZDHHC22 (ENSG00000177108), ZDHHC23 (ENSG00000184307), ZDHHC9 (ENSG00000188706), ZDHHC11 (ENSG00000188818), ZDHHC18 (ENSG00000204160), ZDHHC11B (ENSG00000206077)

Protein

Protein identifiers

Palmitoyltransferase ZDHHC20 — Q5W0Z9 (reviewed: Q5W0Z9)

Alternative names: Acyltransferase ZDHHC20, DHHC domain-containing cysteine-rich protein 20, Zinc finger DHHC domain-containing protein 20

All UniProt accessions (4): A0A0D9SEN4, A0A8V8TR49, B4DRN8, Q5W0Z9

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates. Catalyzes palmitoylation of Cys residues in the cytoplasmic C-terminus of EGFR, and modulates the duration of EGFR signaling by modulating palmitoylation-dependent EGFR internalization and degradation. Has a preference for acyl-CoA with C16 fatty acid chains. Can also utilize acyl-CoA with C14 and C18 fatty acid chains. May palmitoylate CALHM1 subunit of gustatory voltage-gated ion channels and modulate channel gating and kinetics. (Microbial infection) Dominant palmitoyltransferase responsible for lipidation of SARS coronavirus-2/SARS-CoV-2 spike protein. Through a sequential action with ZDHHC9, rapidly and efficiently palmitoylates spike protein following its synthesis in the endoplasmic reticulum (ER). In the infected cell, promotes spike biogenesis by protecting it from premature ER degradation, increases half-life and controls the lipid organization of its immediate membrane environment. Once the virus has formed, spike palmitoylation controls fusion with the target cell.

Subcellular location. Golgi apparatus membrane. Cell membrane. Cytoplasm. Perinuclear region. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane.

Post-translational modifications. Autopalmitoylated (in vitro).

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

Similarity. Belongs to the DHHC palmitoyltransferase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5W0Z9-1	1	yes
Q5W0Z9-2	2
Q5W0Z9-3	3
Q5W0Z9-4	4

RefSeq proteins (3): NP_001273567, NP_001316988, NP_694983 (=MANE)

Domains & families (InterPro)

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

Pfam: PF01529

Catalyzed reactions (Rhea), 3 shown:

• L-cysteinyl-[protein] + hexadecanoyl-CoA = S-hexadecanoyl-L-cysteinyl-[protein] + CoA (RHEA:36683)
• L-cysteinyl-[protein] + tetradecanoyl-CoA = S-tetradecanoyl-L-cysteinyl-[protein] + CoA (RHEA:59736)
• L-cysteinyl-[protein] + octadecanoyl-CoA = S-octadecanoyl-L-cysteinyl-[protein] + CoA (RHEA:59740)

UniProt features (72 total): mutagenesis site 15, helix 13, binding site 10, turn 6, strand 6, topological domain 5, splice variant 5, transmembrane region 4, modified residue 3, site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6BMN	X-RAY DIFFRACTION	2.25
6BMM	X-RAY DIFFRACTION	2.35
7KHM	X-RAY DIFFRACTION	2.88
6BML	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W0Z9-F1	86.11	0.78

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 (3): 156 (s-palmitoyl cysteine intermediate); 29 (important for selectivity toward medium-length fatty acids); 181 (important for selectivity toward medium-length fatty acids)

Ligand- & substrate-binding residues (10): 128; 131; 135; 140–143; 141; 142; 145; 148; 155; 162

Post-translational modifications (3): 305, 330, 339

Mutagenesis-validated functional residues (15):

Position	Phenotype
22	strongly reduced catalytic activity.
29	strongly reduced catalytic activity. enhances activity with acyl-coa with c12 and c14 fatty acid chains.
153	loss of catalytic activity.
154	loss of catalytic activity.
156	loss of catalytic activity.
158	strongly reduced catalytic activity.
171	loss of catalytic activity.
174	strongly reduced catalytic activity.
181	moderately reduced catalytic activity. enhances activity with acyl-coa with c18 and c20 fatty acid chains.
227	loss of catalytic activity.
240–241	loss of catalytic activity.
243	mildly reduced catalytic activity.
266	strongly reduced catalytic activity.
267	loss of catalytic activity.
271	mildly reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9694548	Maturation of spike protein

MSigDB gene sets: 161 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_VESICLE_ORGANIZATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_PROTEIN_TARGETING, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_PEPTIDYL_CYSTEINE_MODIFICATION, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_PROCESS, DOUGLAS_BMI1_TARGETS_UP, GOBP_PROTEIN_ACYLATION

GO Biological Process (6): protein targeting to membrane (GO:0006612), synaptic vesicle maturation (GO:0016188), peptidyl-L-cysteine S-palmitoylation (GO:0018230), protein palmitoylation (GO:0018345), host-mediated activation of viral process (GO:0044794), virion attachment to host cell (GO:0019062)

GO Molecular Function (9): zinc ion binding (GO:0008270), palmitoyltransferase activity (GO:0016409), protein-cysteine S-myristoyltransferase activity (GO:0019705), protein-cysteine S-palmitoyltransferase activity (GO:0019706), protein-cysteine S-stearoyltransferase activity (GO:0140439), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872)

GO Cellular Component (9): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Translation of Structural Proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-cysteine S-acyltransferase activity	3
cytoplasm	3
cellular anatomical structure	3
bounding membrane of organelle	2
endomembrane system	2
intracellular membrane-bounded organelle	2
protein targeting	1
establishment of protein localization to membrane	1
vesicle organization	1
developmental maturation	1
peptidyl-S-diacylglycerol-L-cysteine biosynthetic process from peptidyl-cysteine	1
protein palmitoylation	1
protein lipidation	1
protein acylation	1
host-mediated perturbation of viral process	1
viral life cycle	1
adhesion of symbiont to host cell	1
virion binding	1
host cell surface binding	1
transition metal ion binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
myristoyltransferase activity	1
palmitoyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endoplasmic reticulum-Golgi intermediate compartment	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZDHHC20	EEF1AKMT1	Q8WVE0	578
ZDHHC20	ZDHHC22	Q8N966	520
ZDHHC20	GOLGA7	Q7Z5G4	490
ZDHHC20	GOLGA7B	Q2TAP0	464
ZDHHC20	RNF17	Q9BXT8	432
ZDHHC20	ZDHHC21	Q8IVQ6	413
ZDHHC20	MICU2	Q8IYU8	408
ZDHHC20	ABHD17A	Q96GS6	402
ZDHHC20	ZDHHC17	Q8IUH5	395
ZDHHC20	ZDHHC13	Q8IUH4	389
ZDHHC20	RPS6KA1	Q15418	380
ZDHHC20	ZDHHC6	Q9H6R6	366
ZDHHC20	LYPLA1	O75608	360
ZDHHC20	ATP12A	P54707	348
ZDHHC20	PPT1	P50897	348

IntAct

30 interactions, top by confidence:

A	B	Type	Score
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
S	ZDHHC20	psi-mi:“MI:0216”(palmitoylation reaction)	0.440
CCL1	ZDHHC20	psi-mi:“MI:0915”(physical association)	0.370
	ZDHHC20	psi-mi:“MI:0915”(physical association)	0.370
LTA	ZDHHC20	psi-mi:“MI:0915”(physical association)	0.370
	SHTN1	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
BACE2	FAM171A2	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
TSPAN8	TP53I11	psi-mi:“MI:0914”(association)	0.350
MBLAC2	CD63	psi-mi:“MI:0914”(association)	0.350
BTC	VSIG8	psi-mi:“MI:0914”(association)	0.350
CD151	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
KCNE3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TSPAN8	POTEF	psi-mi:“MI:0914”(association)	0.350
TSPAN3	SCAMP3	psi-mi:“MI:0914”(association)	0.350
LAT	ZDHHC20	psi-mi:“MI:0914”(association)	0.350
SLC18A2	LGALS8	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (54): ZDHHC20 (Proximity Label-MS), ZDHHC20 (Affinity Capture-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Affinity Capture-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Affinity Capture-MS), S (Biochemical Activity), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS), ZDHHC20 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IDP3, A0A0R4IF99, A0PK84, B0S5D5, E7F021, E7F587, F1Q7H8, F1QAM1, F1QGD2, F1QHM7, F1QX91, F1QXD3, F1RE57, O74384, P0C7U3, P42836, Q06551, Q0VC89, Q2TGI8, Q2TGJ4, Q500Z2, Q58DT3, Q5BLG4, Q5FVR1, Q5FWL7, Q5M757, Q5W0Z9, Q5Y5T1, Q5Y5T3, Q6CPU8, Q6DHI1, Q6FSS4, Q6FW70, Q750R7, Q75AW7, Q7XA86, Q8BGJ0, Q8I0G4, Q8VYP5, Q91WU6

Diamond homologs: A0A0R4IDP3, A2CEX1, A2VEY9, A5WVX9, B3DN87, C8VCL4, E1BLT8, E7F021, E7F587, E7FBS9, E7FH11, E9PTT0, E9QCD3, F1Q7H8, F1QAM1, F1QHM7, F1QX91, F1QXD3, F1R013, F1RE57, J9VJ99, O60069, O74384, O80685, P42836, P59267, P59268, Q04629, Q0VC89, Q10L01, Q2TGJ1, Q2TGJ4, Q2TGK3, Q2THW7, Q2THW8, Q2THW9, Q2THX0, Q2THX1, Q4R690, Q4WZL8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DAP12 signaling	5	102.3×	1e-07
RAF/MAP kinase cascade	6	20.4×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	38.1×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3002 predictions. Top by Δscore:

Variant	Effect	Δscore
13:21376483:A:AC	donor_gain	1.0000
13:21376484:A:C	donor_gain	1.0000
13:21381428:TATTA:T	donor_loss	1.0000
13:21381429:ATTAC:A	donor_loss	1.0000
13:21381430:TTAC:T	donor_loss	1.0000
13:21381431:TA:T	donor_loss	1.0000
13:21381432:ACCT:A	donor_loss	1.0000
13:21381545:CACTA:C	acceptor_gain	1.0000
13:21381546:ACTA:A	acceptor_loss	1.0000
13:21381547:CTA:C	acceptor_gain	1.0000
13:21381548:TA:T	acceptor_gain	1.0000
13:21381550:C:CA	acceptor_loss	1.0000
13:21381550:C:CC	acceptor_gain	1.0000
13:21381551:T:A	acceptor_loss	1.0000
13:21382915:CATAC:C	donor_loss	1.0000
13:21382917:TACC:T	donor_loss	1.0000
13:21382919:CCTT:C	donor_gain	1.0000
13:21383005:CCAAG:C	acceptor_gain	1.0000
13:21383006:CAAG:C	acceptor_gain	1.0000
13:21383006:CAAGC:C	acceptor_gain	1.0000
13:21383007:AAG:A	acceptor_gain	1.0000
13:21383007:AAGCT:A	acceptor_loss	1.0000
13:21383008:AG:A	acceptor_gain	1.0000
13:21383009:GCTG:G	acceptor_loss	1.0000
13:21383010:C:A	acceptor_loss	1.0000
13:21383010:C:CC	acceptor_gain	1.0000
13:21383014:A:C	acceptor_gain	1.0000
13:21383017:A:AC	acceptor_gain	1.0000
13:21383017:A:C	acceptor_gain	1.0000
13:21387503:ATTAC:A	donor_loss	1.0000

AlphaMissense

2400 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:21382998:C:T	G289D	1.000
13:21387585:G:C	F259L	1.000
13:21387585:G:T	F259L	1.000
13:21387587:A:G	F259L	1.000
13:21391730:G:A	T240I	1.000
13:21391748:A:G	L234P	1.000
13:21391758:G:C	H231D	1.000
13:21391780:G:C	S223R	1.000
13:21391780:G:T	S223R	1.000
13:21391782:T:G	S223R	1.000
13:21400454:G:C	F171L	1.000
13:21400454:G:T	F171L	1.000
13:21400456:A:G	F171L	1.000
13:21400466:A:C	N167K	1.000
13:21400466:A:T	N167K	1.000
13:21400476:C:T	G164E	1.000
13:21400481:A:C	C162W	1.000
13:21400482:C:A	C162F	1.000
13:21400482:C:T	C162Y	1.000
13:21400483:A:G	C162R	1.000
13:21401654:A:G	W158R	1.000
13:21401654:A:T	W158R	1.000
13:21401658:A:C	C156W	1.000
13:21401659:C:A	C156F	1.000
13:21401659:C:G	C156S	1.000
13:21401659:C:T	C156Y	1.000
13:21401660:A:G	C156R	1.000
13:21401660:A:T	C156S	1.000
13:21401661:G:C	H155Q	1.000
13:21401661:G:T	H155Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000002909 (13:21402149 G>A), RS1000005849 (13:21373831 G>C), RS1000054998 (13:21406436 C>T), RS1000059890 (13:21374181 A>T), RS1000091556 (13:21410771 A>C), RS1000106166 (13:21449834 G>A), RS1000136642 (13:21398488 A>G,T), RS1000165841 (13:21398597 T>C), RS1000168289 (13:21436978 TA>T,TAA), RS1000236693 (13:21411883 C>A,T), RS1000237448 (13:21454789 C>G,T), RS1000273545 (13:21445427 A>T), RS1000280101 (13:21433591 T>C,G), RS1000299024 (13:21398664 T>C), RS1000327359 (13:21417830 A>G)

Disease associations

OMIM: gene MIM:617972 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001859_16	Thiazide-induced adverse metabolic effects in hypertensive patients	4.000000e-06
GCST003013_34	White matter hyperintensity burden	4.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169156 (SINGLE PROTEIN)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 10 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.87	IC50	1350	nM	CHEMBL5201039
5.71	IC50	1970	nM	CHEMBL5186346
5.54	IC50	2870	nM	CHEMBL5199102
5.46	IC50	3450	nM	CHEMBL5205503
5.46	IC50	3430	nM	CHEMBL5191244
5.26	IC50	5550	nM	CHEMBL118417
5.01	IC50	9730	nM	CHEMBL5181387

PubChem BioAssay actives

8 with measured affinity, of 40 total; 7 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(cyanomethyl)-N-tetradecylprop-2-enamide	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	1.3500	uM
N-(cyanomethyl)-N-(2-undecoxyethyl)prop-2-enamide	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	1.9700	uM
cyanomethyl (Z)-4-oxo-4-(tetradecylamino)but-2-enoate	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	2.8700	uM
prop-2-ynyl (Z)-4-oxo-4-(tetradecylamino)but-2-enoate	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	3.4300	uM
(Z)-4-[cyanomethyl(tetradecyl)amino]-4-oxobut-2-enoic acid	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	3.4500	uM
2-bromohexadecanoic acid	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	5.5500	uM
[1-[3-[3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]propyl]triazol-4-yl]methyl (Z)-4-oxo-4-(tetradecylamino)but-2-enoate	1875525: Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay	ic50	9.7300	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation	1
kojic acid	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
homosalate	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Doxorubicin	decreases expression	1
Gold	decreases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Polystyrenes	affects cotreatment, increases expression	1
Dihydrotestosterone	increases expression	1
Cyclosporine	affects expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5131018	Binding	Inhibition of human myc-His6-tagged zDHHC20 expressed in HEK293T cells at 10 uM using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 1 hr followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmito	Charting the Chemical Space of Acrylamide-Based Inhibitors of zDHHC20. — ACS Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1MH	HyCyte A-549 KO-hZDHHC20	Cancer cell line	Male
CVCL_TY85	HAP1 ZDHHC20 (-) 1	Cancer cell line	Male
CVCL_TY86	HAP1 ZDHHC20 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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