LYPLA2

Summary

LYPLA2 (lysophospholipase 2, HGNC:6738) is a protein-coding gene on chromosome 1p36.11, encoding Acyl-protein thioesterase 2 (O95372). Acts as an acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins, GSDMD, GAP43, ZDHHC6 or HRAS.

Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. There are alternatively spliced transcript variants described for this gene but the full length nature is not known yet.

Source: NCBI Gene 11313 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007260

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6738
Approved symbol	LYPLA2
Name	lysophospholipase 2
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	APT-2, APT2
Ensembl gene	ENSG00000011009
Ensembl biotype	protein_coding
OMIM	616143
Entrez	11313

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000374501, ENST00000374502, ENST00000374503, ENST00000374505, ENST00000374514, ENST00000420982, ENST00000421070, ENST00000472213, ENST00000492577, ENST00000495365, ENST00000905307, ENST00000905308, ENST00000905309, ENST00000905310, ENST00000905312, ENST00000905314, ENST00000905316, ENST00000905317, ENST00000905318, ENST00000905319, ENST00000926742, ENST00000926743, ENST00000926744, ENST00000926745, ENST00000926746, ENST00000957285, ENST00000957286

RefSeq mRNA: 1 — MANE Select: NM_007260 NM_007260

CCDS: CCDS241

Canonical transcript exons

ENST00000374514 — 10 exons

Exon	Start	End
ENSE00001709031	23794682	23795539
ENSE00001872802	23791145	23791250
ENSE00003526973	23793705	23793752
ENSE00003565881	23794063	23794136
ENSE00003582846	23794427	23794600
ENSE00003589232	23793860	23793930
ENSE00003645214	23794224	23794325
ENSE00003683923	23793151	23793216
ENSE00003693552	23793008	23793039
ENSE00004020618	23792657	23792760

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6022 / max 80.8197, expressed in 1788 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1366	4.3133	1679
1365	2.9816	1548
1367	2.9439	1345
201407	0.6184	356
1368	0.5110	273
1369	0.1609	70
1370	0.0731	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.18	gold quality
mucosa of transverse colon	UBERON:0004991	97.10	gold quality
right uterine tube	UBERON:0001302	97.03	gold quality
metanephros cortex	UBERON:0010533	96.61	gold quality
granulocyte	CL:0000094	96.46	gold quality
pancreatic ductal cell	CL:0002079	96.05	gold quality
ileal mucosa	UBERON:0000331	95.58	gold quality
esophagus mucosa	UBERON:0002469	95.30	gold quality
right lobe of liver	UBERON:0001114	94.89	gold quality
adult mammalian kidney	UBERON:0000082	94.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.65	gold quality
minor salivary gland	UBERON:0001830	94.64	gold quality
transverse colon	UBERON:0001157	94.55	gold quality
body of stomach	UBERON:0001161	94.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.34	gold quality
skin of leg	UBERON:0001511	94.11	gold quality
skin of abdomen	UBERON:0001416	94.03	gold quality
spleen	UBERON:0002106	94.03	gold quality
apex of heart	UBERON:0002098	93.95	gold quality
mouth mucosa	UBERON:0003729	93.85	gold quality
small intestine	UBERON:0002108	93.50	gold quality
right lobe of thyroid gland	UBERON:0001119	93.49	gold quality
tongue squamous epithelium	UBERON:0006919	93.46	silver quality
saliva-secreting gland	UBERON:0001044	93.44	gold quality
monocyte	CL:0000576	93.26	gold quality
leukocyte	CL:0000738	93.25	gold quality
upper lobe of left lung	UBERON:0008952	93.24	gold quality
esophagus	UBERON:0001043	93.17	gold quality
mononuclear cell	CL:0000842	93.14	gold quality
upper lobe of lung	UBERON:0008948	93.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.08
E-MTAB-6524	no	116.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting LYPLA2, 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-4481	100.00	66.42	1669
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-125A-5P	99.36	70.59	1640

Literature-anchored findings (GeneRIF, showing 6)

• Results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution. (PMID:21152083)
• Dynamic palmitoylation links cytosol-membrane shuttling of acyl-protein thioesterase-1 and acyl-protein thioesterase-2 with that of proto-oncogene H-ras product and growth-associated protein-43 (PMID:23396970)
• LYPLA2 is the major prostaglandin glycerol ester hydrolase in human cancer cells. (PMID:25301951)
• Here, we describe the conserved functions of APT1 and APT2 across organisms and discuss the possibility that these enzymes are members of a larger family of depalmitoylation enzymes. (PMID:25849916)
• LYPLA1 and LYPLA2 are each able to account for the loss of the other to maintain lipid homeostasis in cells (PMID:30482805)
• Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains. (PMID:33707782)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lypla2	ENSDARG00000053656
mus_musculus	Lypla2	ENSMUSG00000028670
rattus_norvegicus	Lypla2	ENSRNOG00000010067
caenorhabditis_elegans	ath-1	WBGENE00010564

Paralogs (2): LYPLA1 (ENSG00000120992), LYPLAL1 (ENSG00000143353)

Protein

Protein identifiers

Acyl-protein thioesterase 2 — O95372 (reviewed: O95372)

Alternative names: Lysophospholipase II, Palmitoyl-protein hydrolase

All UniProt accessions (6): O95372, A0A140VJC9, Q5QPN5, Q5QPQ0, Q5QPQ1, Q5QPQ2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins, GSDMD, GAP43, ZDHHC6 or HRAS. Deacylates GAP43. Mediates depalmitoylation of ZDHHC6. Has lysophospholipase activity. Hydrolyzes prostaglandin glycerol esters (PG-Gs) in the following order prostaglandin D2-glycerol ester (PGD2-G) > prostaglandin E2 glycerol ester (PGE2-G) > prostaglandin F2-alpha-glycerol ester (PGF2-alpha-G). Hydrolyzes 1-arachidonoylglycerol but not 2-arachidonoylglycerol or arachidonoylethanolamide.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in various breast cancer cell lines.

Activity regulation. Inhibited by compound 1 or (5,5-Dioxido-4H-thieno[3,2-c]thiochromen-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone.

Similarity. Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.

RefSeq proteins (1): NP_009191* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003140	PLipase/COase/thioEstase	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050565	LYPA1-2/EST-like	Family

Pfam: PF02230

Catalyzed reactions (Rhea), 6 shown:

• S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+) (RHEA:19233)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + hexadecanoate + H(+) (RHEA:40435)
• 1-octadecanoyl-sn-glycero-3-phosphocholine + H2O = octadecanoate + sn-glycerol 3-phosphocholine + H(+) (RHEA:40887)
• 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H2O = sn-glycero-3-phospho-L-serine + hexadecanoate + H(+) (RHEA:44552)
• prostaglandin E2 1-glyceryl ester + H2O = prostaglandin E2 + glycerol + H(+) (RHEA:48296)
• 1-hexadecanoyl-sn-glycero-3-phosphate + H2O = sn-glycerol 3-phosphate + hexadecanoate + H(+) (RHEA:49092)

UniProt features (30 total): strand 11, helix 10, active site 3, mutagenesis site 2, chain 1, turn 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5SYN	X-RAY DIFFRACTION	1.64
6BJE	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95372-F1	95.92	0.94

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): 122 (charge relay system); 176 (charge relay system); 210 (charge relay system)

Post-translational modifications (2): 82, 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
2	abolishes palmitoylation.
122	abolishes ability to mediate depalmitoylation of zdhhc6.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-373760	L1CAM interactions
R-HSA-1266738	Developmental Biology
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 172 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MORF_UBE2I, GOBP_MACROMOLECULE_DEACYLATION, GOBP_NEUROGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, YY1_Q6, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, NFKB_C, YY1_02, MORF_CTBP1, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (6): fatty acid metabolic process (GO:0006631), axon guidance (GO:0007411), acylglycerol catabolic process (GO:0046464), prostaglandin catabolic process (GO:1905344), lipid metabolic process (GO:0006629), macromolecule depalmitoylation (GO:0098734)

GO Molecular Function (5): phosphatidylcholine lysophospholipase A1 activity (GO:0004622), palmitoyl-(protein) hydrolase activity (GO:0008474), cadherin binding (GO:0045296), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi stack (GO:0005795), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lipid metabolic process	1
monocarboxylic acid metabolic process	1
axonogenesis	1
neuron projection guidance	1
acylglycerol metabolic process	1
neutral lipid catabolic process	1
glycerolipid catabolic process	1
prostanoid catabolic process	1
primary metabolic process	1
macromolecule deacylation	1
lysophospholipase A1 activity	1
thiolester hydrolase activity	1
palmitoyl hydrolase activity	1
catalytic activity, acting on a protein	1
cell adhesion molecule binding	1
binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
Golgi apparatus subcompartment	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPLA2	PPT1	P50897	646
LYPLA2	ABHD17A	Q96GS6	616
LYPLA2	ZDHHC7	Q9NXF8	597
LYPLA2	ABHD13	Q7L211	589
LYPLA2	ZDHHC6	Q9H6R6	560
LYPLA2	PPT2	Q9UMR5	532
LYPLA2	ABHD11	Q8NFV4	530
LYPLA2	ZDHHC16	Q969W1	516
LYPLA2	ZDHHC24	Q6UX98	512
LYPLA2	ABHD17B	Q5VST6	500
LYPLA2	ABHD12	Q8N2K0	496
LYPLA2	ABHD10	Q9NUJ1	490
LYPLA2	ABHD6	Q9BV23	490
LYPLA2	ZDHHC17	Q8IUH5	490
LYPLA2	ZDHHC3	Q9NYG2	487

IntAct

42 interactions, top by confidence:

A	B	Type	Score
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LYPLA2	INCA1	psi-mi:“MI:0915”(physical association)	0.560
NYX	LYPLA2	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
LYPLA2	NUMA1	psi-mi:“MI:0915”(physical association)	0.400
S	LYPLA2	psi-mi:“MI:0915”(physical association)	0.400
LRRK2		psi-mi:“MI:0914”(association)	0.350
KIF3A	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
SGO2	DUSP14	psi-mi:“MI:0914”(association)	0.350
MLST8	LYPLA2	psi-mi:“MI:0914”(association)	0.350
pipB2	PSMD12	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
NYX	POTEF	psi-mi:“MI:0914”(association)	0.350
HSPE1	LYPLA2	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
NPSR1	DUSP14	psi-mi:“MI:0914”(association)	0.350
ALDH3B1	ENC1	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
OSBPL11	DNM1L	psi-mi:“MI:0914”(association)	0.350
VCAM1		psi-mi:“MI:0914”(association)	0.350

BioGRID (76): LYPLA2 (Affinity Capture-MS), LYPLA2 (Affinity Capture-MS), LYPLA2 (Affinity Capture-MS), APRT (Co-fractionation), EIF2B1 (Co-fractionation), LACTB2 (Co-fractionation), LYPLA2 (Co-fractionation), LYPLA2 (Co-fractionation), LYPLA2 (Co-fractionation), LYPLA2 (Co-fractionation), LYPLA2 (Co-fractionation), LYPLA2 (Co-fractionation), SPR (Co-fractionation), LYPLA2 (Affinity Capture-MS), LYPLA2 (Proximity Label-MS)

ESM2 similar proteins: A1YER2, A1YFX9, A2T7G9, B0BNF8, F6V515, O88767, O95372, P12863, P17764, P21820, P29401, P32929, P40142, P48494, P48758, P50137, P78330, P82197, P93394, Q0II59, Q148G4, Q2KHU0, Q3ZBV9, Q5E946, Q5I0K3, Q5R4C1, Q5RB83, Q5XJ36, Q60HC7, Q60HG7, Q6B855, Q6P1N9, Q6P8M1, Q6UWP2, Q71R50, Q7TQ35, Q7Z6V5, Q7ZV22, Q8QZT1, Q8TDX5

Diamond homologs: O42881, O75608, O77821, O95372, P0CL94, P0CL95, P70470, P97823, Q0J969, Q12354, Q3MHR0, Q3UFF7, Q4I8Q4, Q4PID3, Q4WCX7, Q54T49, Q55FK4, Q5AGD1, Q5ASI2, Q5R8C2, Q5RBR7, Q5VWZ2, Q6BSS8, Q6CGL4, Q6CJK6, Q6FW75, Q750X7, Q7XR62, Q84WK4, Q8GYK2, Q9HFJ5, Q9QYL8, Q9WTL7, Q51758, Q53547, Q0J968

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
LYPLA2	“down-regulates quantity by destabilization”	GAP43	deacetylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1742 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23791157:G:GT	donor_gain	1.0000
1:23791232:G:GT	donor_gain	1.0000
1:23791242:G:GT	donor_gain	1.0000
1:23793212:CATGC:C	donor_gain	1.0000
1:23793213:ATGC:A	donor_gain	1.0000
1:23793215:GC:G	donor_gain	1.0000
1:23793217:G:GG	donor_gain	1.0000
1:23793753:G:GA	donor_loss	1.0000
1:23793753:G:GG	donor_gain	1.0000
1:23793931:G:GG	donor_gain	1.0000
1:23794061:A:AG	acceptor_gain	1.0000
1:23794062:G:GG	acceptor_gain	1.0000
1:23794219:TCCAG:T	acceptor_loss	1.0000
1:23794220:CCA:C	acceptor_loss	1.0000
1:23794221:CAGGG:C	acceptor_loss	1.0000
1:23794222:A:AG	acceptor_gain	1.0000
1:23794222:AG:A	acceptor_gain	1.0000
1:23794222:AGGGC:A	acceptor_gain	1.0000
1:23794223:G:GC	acceptor_gain	1.0000
1:23794223:GG:G	acceptor_gain	1.0000
1:23794223:GGGC:G	acceptor_gain	1.0000
1:23794223:GGGCG:G	acceptor_gain	1.0000
1:23791157:G:T	donor_gain	0.9900
1:23791248:G:GT	donor_gain	0.9900
1:23791274:G:GT	donor_gain	0.9900
1:23791278:G:GT	donor_gain	0.9900
1:23792718:C:A	acceptor_gain	0.9900
1:23792758:GCG:G	donor_gain	0.9900
1:23792759:CGG:C	donor_loss	0.9900
1:23792761:G:GG	donor_gain	0.9900

AlphaMissense

1500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23793861:T:C	F76L	1.000
1:23793863:T:A	F76L	1.000
1:23793863:T:G	F76L	1.000
1:23794128:T:C	F121L	1.000
1:23794130:T:A	F121L	1.000
1:23794130:T:G	F121L	1.000
1:23793024:G:A	G32E	0.999
1:23793030:G:A	G34E	0.999
1:23793030:G:T	G34V	0.999
1:23793158:T:A	W40R	0.999
1:23793158:T:C	W40R	0.999
1:23793206:T:C	C56R	0.999
1:23793749:C:T	S74F	0.999
1:23793751:T:A	W75R	0.999
1:23793751:T:C	W75R	0.999
1:23793860:G:C	W75C	0.999
1:23793860:G:T	W75C	0.999
1:23794111:G:C	R115P	0.999
1:23794117:T:A	V117D	0.999
1:23794123:G:A	G119E	0.999
1:23794126:G:A	G120D	0.999
1:23794129:T:C	F121S	0.999
1:23794131:T:C	S122P	0.999
1:23794132:C:T	S122L	0.999
1:23794136:G:C	Q123H	0.999
1:23794136:G:T	Q123H	0.999
1:23794224:G:C	G124R	0.999
1:23794224:G:T	G124C	0.999
1:23794225:G:T	G124V	0.999
1:23794227:G:T	G125W	0.999

dbSNP variants (sampled 300 via entrez): RS1000219306 (1:23793275 G>C), RS1000550545 (1:23794865 G>C), RS1000581853 (1:23795229 CCT>C), RS1001238801 (1:23791436 A>G), RS1001270190 (1:23791840 G>C), RS1001846260 (1:23791243 G>C,T), RS1001898661 (1:23791635 C>T), RS1003142382 (1:23795504 T>C), RS1003509160 (1:23790029 C>G,T), RS1003571506 (1:23790275 G>A), RS1003578910 (1:23790259 T>A,G), RS1003610037 (1:23790482 C>T), RS1004113061 (1:23793527 C>T), RS1004362299 (1:23793369 C>A), RS1004818824 (1:23793626 G>A,T)

Disease associations

OMIM: gene MIM:616143 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1932891 (SINGLE PROTEIN), CHEMBL4680048 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
ML211	Inhibition	7.52	pIC50
Palmostatin B	Inhibition	7.42	pIC50
ML349	Inhibition	6.64	pKi

Binding affinities (BindingDB)

3 measured of 22 human assays (23 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
ML349	KI	180 nM
ML349-FL	KD	770 nM
ML349-sulfoxide	KD	2600 nM

ChEMBL bioactivities

19 potent at pChembl≥5 of 20 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.71	IC50	19.6	nM	CHEMBL3133031
7.71	IC50	19.58	nM	PALMOSTATIN B
7.62	IC50	23.72	nM	CHEMBL5562679
7.52	IC50	30	nM	CHEMBL1903566
7.49	IC50	32.44	nM	CHEMBL5565391
7.47	Ki	34	nM	PALMOSTATIN B
7.43	IC50	36.74	nM	CHEMBL5568560
7.42	IC50	37.7	nM	PALMOSTATIN B
7.19	IC50	64.44	nM	CHEMBL5565657
6.92	Ki	120	nM	CHEMBL1509398
6.70	IC50	200	nM	CHEMBL3133033
6.64	Ki	230	nM	CHEMBL1509398
6.14	Ki	730	nM	CHEMBL3133032
5.96	Ki	1100	nM	CHEMBL3944678
5.96	IC50	1100	nM	CHEMBL1509398
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

47 with measured affinity, of 84 total; 29 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
(3S,4S)-3-decyl-4-[2-(3,4-dimethoxyphenyl)ethyl]oxetan-2-one	2084119: Inhibition of APT2 (unknown origin)	ic50	0.0196	uM
(3S,4S)-3-decyl-4-[4-[3-(dimethylamino)propylsulfonyl]butyl]oxetan-2-one	1079562: Inhibition of APT2 (unknown origin)	ic50	0.0196	uM
(3S,4S)-3-dec-9-ynyl-4-[2-(3,4-dimethoxyphenyl)ethyl]oxetan-2-one	2084119: Inhibition of APT2 (unknown origin)	ic50	0.0237	uM
(4-tert-butylpiperidin-1-yl)-[4-[hydroxy(diphenyl)methyl]triazol-2-yl]methanone	1079559: Inhibition of human APT2	ic50	0.0300	uM
(3S,4S)-4-dec-9-ynyl-3-[4-[3-(dimethylamino)propylsulfonyl]butyl]oxetan-2-one	2084119: Inhibition of APT2 (unknown origin)	ic50	0.0324	uM
(3S,4S)-4-decyl-3-[4-[3-(dimethylamino)propylsulfonyl]butyl]oxetan-2-one	2084119: Inhibition of APT2 (unknown origin)	ic50	0.0367	uM
(3S,4S)-4-decyl-3-[4-[3-[methyl(pent-4-ynyl)amino]propylsulfonyl]butyl]oxetan-2-one	2084119: Inhibition of APT2 (unknown origin)	ic50	0.0644	uM
(5,5-dioxo-4H-thieno[3,2-c]thiochromen-2-yl)-[4-(4-methoxyphenyl)piperazin-1-yl]methanone	1339519: Competitive inhibition of HEK293T cells-derived His-tagged APT2 expressed in Escherichia coli BL21(DE3) preincubated for 30 mins followed by substrate addition by resorufin dye based acetate hydrolysis assay	ki	0.1200	uM
(3,4-dichlorophenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	0.1380	uM
[4-[hydroxy(diphenyl)methyl]triazol-2-yl]-piperidin-1-ylmethanone	1079559: Inhibition of human APT2	ic50	0.2000	uM
(2-iodo-5-phenoxyphenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	0.2380	uM
(3-chlorophenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	0.4180	uM
N-[2-chloro-5-(trifluoromethyl)phenyl]-2-[4-(furan-2-carbonyl)piperazin-1-yl]acetamide	1802281: Steady-State Kinetic Assays from Article 10.1021/acschembio.6b00720: “Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2).”	ki	0.4300	uM
1-benzothiophen-2-ylboronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	0.5290	uM
2-[[4-[[4-[2-(dimethylamino)ethoxy-phenylboranyl]phenyl]methoxymethyl]phenyl]-phenylboranyl]oxy-N,N-dimethylethanamine	1079560: Inhibition of APT2 (unknown origin) by enzyme kinetic assay	ki	0.7300	uM
4-[2-[2-[2-[2-[4-[[4-[4-(5,5-dioxo-4H-thieno[3,2-c]thiochromene-2-carbonyl)piperazin-1-yl]phenoxy]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-2-(3-hydroxy-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid	1802282: Fluorescence Binding Assays from Article 10.1021/acschembio.6b00720: “Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2).”	kd	0.7700	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[4-[[4-[4-(5,5-dioxo-4H-thieno[3,2-c]thiochromene-2-carbonyl)piperazin-1-yl]phenoxy]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl]pentanamide	1339519: Competitive inhibition of HEK293T cells-derived His-tagged APT2 expressed in Escherichia coli BL21(DE3) preincubated for 30 mins followed by substrate addition by resorufin dye based acetate hydrolysis assay	ki	1.1000	uM
2-[[3-[[3-[2-aminoethoxy(phenyl)boranyl]phenyl]methoxymethyl]phenyl]-phenylboranyl]oxyethanamine	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	1.6000	uM
2-[[3-[[3-[2-(dimethylamino)ethoxy-phenylboranyl]phenyl]methoxymethyl]phenyl]-phenylboranyl]oxy-N,N-dimethylethanamine	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	1.8000	uM
(3,5-difluorophenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	1.9700	uM
(4-bromothiophen-3-yl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	1.9800	uM
(2-bromo-5-methylphenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	2.1600	uM
(3-acetylphenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	2.8700	uM
(3-methoxycarbonyl-5-nitrophenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	2.9500	uM
(4-phenylphenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	3.5500	uM
2-[[4-[[4-[2-aminoethoxy(phenyl)boranyl]phenyl]methoxymethyl]phenyl]-phenylboranyl]oxyethanamine	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	4.1000	uM
(4-chlorophenyl)boronic acid	1799826: Enzymatic Protein Activity Assay from Article 10.1002/cbic.201200571: “Boron-based inhibitors of acyl protein thioesterases 1 and 2.”	ic50	4.1800	uM
[4-(4-methoxyphenyl)piperazin-1-yl]-(5-oxo-4H-thieno[3,2-c]thiochromen-2-yl)methanone	1802282: Fluorescence Binding Assays from Article 10.1021/acschembio.6b00720: “Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2).”	kd	5.2000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178623: Inhibition of LYPLA2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases expression	4
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
prostaglandin E2 glyceryl ester	increases hydrolysis	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
Arsenic Trioxide	affects binding, decreases reaction	1
Arachidonic Acids	increases hydrolysis	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Doxorubicin	increases expression	1
Glycerides	increases hydrolysis	1
Ivermectin	decreases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tretinoin	affects cotreatment, increases expression	1
Vitamin E	increases expression, affects cotreatment	1

ChEMBL screening assays

25 unique, capped per target: 25 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1937247	Binding	Inhibition of APT2 at 50 uM	Design, synthesis and evaluation of polar head group containing 2-keto-oxazole inhibitors of FAAH. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WB	Abcam HeLa LYPLA2 KO	Cancer cell line	Female
CVCL_B3AF	Abcam HEK293T LYPLA2 KO	Transformed cell line	Female
CVCL_D8DZ	Ubigene ARPE-19 LYPLA2 KO	Spontaneously immortalized cell line	Male
CVCL_SW12	HAP1 LYPLA2 (-) 1	Cancer cell line	Male
CVCL_SW13	HAP1 LYPLA2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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