LYPLA1

Summary

LYPLA1 (lysophospholipase 1, HGNC:6737) is a protein-coding gene on chromosome 8q11.23, encoding Acyl-protein thioesterase 1 (O75608). Acts as an acyl-protein thioesterase.

This gene encodes a member of the alpha/beta hydrolase superfamily. The encoded protein functions as a homodimer, exhibiting both depalmitoylating as well as lysophospholipase activity, and may be involved in Ras localization and signaling. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 4, 6, and 7.

Source: NCBI Gene 10434 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• MANE Select transcript: NM_006330

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6737
Approved symbol	LYPLA1
Name	lysophospholipase 1
Location	8q11.23
Locus type	gene with protein product
Status	Approved
Aliases	LPL1, APT-1, APT1
Ensembl gene	ENSG00000120992
Ensembl biotype	protein_coding
OMIM	605599
Entrez	10434

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 20 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000316963, ENST00000343231, ENST00000517297, ENST00000518546, ENST00000519272, ENST00000519891, ENST00000519926, ENST00000520718, ENST00000520896, ENST00000521352, ENST00000521856, ENST00000521898, ENST00000522007, ENST00000618741, ENST00000618914, ENST00000873068, ENST00000873069, ENST00000873070, ENST00000873071, ENST00000873072, ENST00000873073, ENST00000873074, ENST00000873075, ENST00000873076, ENST00000928771, ENST00000947148, ENST00000947149

RefSeq mRNA: 7 — MANE Select: NM_006330 NM_001279356, NM_001279357, NM_001279358, NM_001279359, NM_001279360, NM_001425837, NM_006330

CCDS: CCDS6157, CCDS64899, CCDS75738, CCDS75739

Canonical transcript exons

ENST00000316963 — 9 exons

Exon	Start	End
ENSE00002133110	54046367	54048118
ENSE00003492553	54065748	54065813
ENSE00003526116	54063328	54063375
ENSE00003537195	54052655	54052756
ENSE00003614489	54055060	54055133
ENSE00003656650	54100908	54100939
ENSE00003662963	54062254	54062324
ENSE00003677742	54051012	54051188
ENSE00003845856	54101755	54101947

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.0733 / max 183.8512, expressed in 1814 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93095	24.8498	1812
93094	1.2538	654
93093	0.7781	398
93092	0.1088	37
93090	0.0404	9
93091	0.0187	6
93089	0.0168	9
93088	0.0069	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	98.66	gold quality
oral cavity	UBERON:0000167	98.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.20	gold quality
mammalian vulva	UBERON:0000997	98.02	gold quality
heart right ventricle	UBERON:0002080	98.00	gold quality
upper leg skin	UBERON:0004262	97.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.60	gold quality
epithelium of nasopharynx	UBERON:0001951	97.55	gold quality
superior surface of tongue	UBERON:0007371	97.42	gold quality
colonic mucosa	UBERON:0000317	97.32	gold quality
biceps brachii	UBERON:0001507	97.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.29	gold quality
pharyngeal mucosa	UBERON:0000355	97.28	gold quality
jejunal mucosa	UBERON:0000399	97.26	gold quality
jejunum	UBERON:0002115	97.20	gold quality
choroid plexus epithelium	UBERON:0003911	96.99	gold quality
esophagus squamous epithelium	UBERON:0006920	96.89	gold quality
renal medulla	UBERON:0000362	96.77	gold quality
pigmented layer of retina	UBERON:0001782	96.76	gold quality
tongue	UBERON:0001723	96.63	gold quality
placenta	UBERON:0001987	96.54	gold quality
body of tongue	UBERON:0011876	96.50	gold quality
pylorus	UBERON:0001166	96.44	gold quality
right testis	UBERON:0004534	96.40	gold quality
left testis	UBERON:0004533	96.33	gold quality
monocyte	CL:0000576	96.31	gold quality
mononuclear cell	CL:0000842	96.24	gold quality
testis	UBERON:0000473	96.09	gold quality
gingiva	UBERON:0001828	95.99	gold quality
tonsil	UBERON:0002372	95.96	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	965.48
E-GEOD-134144	yes	28.89
E-CURD-88	yes	3.96
E-GEOD-106540	no	581.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

154 targeting LYPLA1, 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-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 14)

• Endogenous and overexpressed hAPT1 were mainly localized in the cytosol, while some signals were detected in the plasma membrane, the nuclear membrane and endoplasmic reticulum in HEK293 cells. (PMID:19439193)
• Results suggest that APT1-regulated depalmitoylation of Galpha(13) might be an important downstream event of miR-138 function. (PMID:19465924)
• identifcation APT1 as one of the thioesterases in the acylation cycle and demonstration that this protein is a cellular target of the inhibitor. (PMID:20418879)
• Serum activity of APT1 may play an important role in determination of the concentration of des-acyl ghrelin in circulation, especially under septic inflammation. (PMID:20685872)
• 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)
• High expression of APT1 is associated with chronic lymphocytic leukemia. (PMID:25670628)
• 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)
• The depalmitoylating enzyme acyl-protein thioesterase 1 (APT1) directs the asymmetric localization of Numb and beta-catenin in MDA-MB-231 triple receptor-negative breast cancer cells. (PMID:29295957)
• Data show taht active S-depalmitoylation in mitochondria, in part mediated by acyl-protein thioesterase 1 (APT1) (PMID:29362370)
• Study results suggest that the LYPLA1 gene plays a tumorpromotor role in nonsmall cell lung cancer cells in vitro. (PMID:30431103)
• LYPLA1 and LYPLA2 are each able to account for the loss of the other to maintain lipid homeostasis in cells (PMID:30482805)
• LncRNA LOXL1-AS1 Facilitates the Oncogenic Character in Cervical Cancer by the miR-526b-5p /LYPLA1 Axis. (PMID:34984578)
• A conserved but structurally divergent loop in acyl protein thioesterase 1 regulates its catalytic activity, ligand binding, and folded stability. (PMID:38179877)
• Depalmitoylation and cell physiology: APT1 as a mediator of metabolic signals. (PMID:38344800)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lypla1	ENSDARG00000104228
mus_musculus	Lypla1	ENSMUSG00000025903
rattus_norvegicus	Lypla1	ENSRNOG00000008320
drosophila_melanogaster	Apt1	FBGN0042138
caenorhabditis_elegans	ath-1	WBGENE00010564

Paralogs (2): LYPLA2 (ENSG00000011009), LYPLAL1 (ENSG00000143353)

Protein

Protein identifiers

Acyl-protein thioesterase 1 — O75608 (reviewed: O75608)

Alternative names: Lysophospholipase 1, Lysophospholipase I, Palmitoyl-protein hydrolase

All UniProt accessions (8): A0A087X1K9, B4DP64, E5RFT6, E5RGR0, E5RI35, E5RJ48, O75608, Q6IAQ1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an acyl-protein thioesterase. Hydrolyzes fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Acts as a palmitoyl thioesterase that catalyzes depalmitoylation of proteins, such as ADRB2, KCNMA1 and SQSTM1. Acts as a negative regulator of autophagy by mediating palmitoylation of SQSTM1, decreasing affinity between SQSTM1 and ATG8 proteins and recruitment of ubiquitinated cargo proteins to autophagosomes. Acts as a lysophospholipase and hydrolyzes lysophosphatidylcholine (lyso-PC). Also hydrolyzes lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-PI) and lysophosphatidylserine (lyso-PS). Has much higher thioesterase activity than lysophospholipase activity. Contributes to the production of lysophosphatidic acid (LPA) during blood coagulation by recognizing and cleaving plasma phospholipids to generate lysophospholipids which in turn act as substrates for ENPP2 to produce LPA.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cell membrane. Nucleus membrane. Endoplasmic reticulum.

Tissue specificity. Platelets.

Activity regulation. Inhibited by palmostatin-B, leading to impair depalmitoylating of Ras.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O75608-1	1	yes
O75608-2	2

RefSeq proteins (7): NP_001266285, NP_001266286, NP_001266287, NP_001266288, NP_001266289, NP_001412766, NP_006321* (*=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

Enzyme classification (BRENDA):

• EC 3.1.2.22 — palmitoyl[protein] hydrolase (BRENDA: 9 organisms, 80 substrates, 16 inhibitors, 7 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PALMITOYL-COA	0.017–0.039	2
1-PALMITOYL LYSOPHOSPHATIDYLCHOLINE	0.0273	1
MYRISTOYL-COA	0.091	1
PALMITOYL-PEPTIDE	0.0035	1
PALMITOYL[BETA-D-THIOGLUCOSIDE	0.227	1

Catalyzed reactions (Rhea), 3 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)
• a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:41720)

UniProt features (31 total): strand 12, helix 9, active site 3, chain 1, turn 1, modified residue 1, splice variant 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1FJ2	X-RAY DIFFRACTION	1.5
5SYM	X-RAY DIFFRACTION	1.55
6QGN	X-RAY DIFFRACTION	2.1
6QGO	X-RAY DIFFRACTION	2.6
6QGQ	X-RAY DIFFRACTION	2.6
6QGS	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75608-F1	95.71	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): 119 (charge relay system); 174 (charge relay system); 208 (charge relay system)

Post-translational modifications (1): 224

Mutagenesis-validated functional residues (1):

Position	Phenotype
119	loss of thioesterase and lysophospholipase activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-203615	eNOS activation
R-HSA-9648002	RAS processing
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-202131	Metabolism of nitric oxide: NOS3 activation and regulation
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling

MSigDB gene sets: 249 (showing top): MORF_MTA1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_AUTOPHAGY, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_MACROMOLECULE_DEACYLATION, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_RAD21, MITSIADES_RESPONSE_TO_APLIDIN_DN, MORF_HDAC2, GOBP_VESICLE_MEDIATED_TRANSPORT, RIZKI_TUMOR_INVASIVENESS_3D_DN, CACCAGC_MIR138, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (9): protein depalmitoylation (GO:0002084), fatty acid metabolic process (GO:0006631), fatty acid transport (GO:0015908), negative regulation of Golgi to plasma membrane protein transport (GO:0042997), negative regulation of aggrephagy (GO:1905336), lipid metabolic process (GO:0006629), aggrephagy (GO:0035973), protein targeting to vacuole involved in autophagy (GO:0071211), macromolecule depalmitoylation (GO:0098734)

GO Molecular Function (6): glycerophospholipase activity (GO:0004620), phosphatidylcholine lysophospholipase A1 activity (GO:0004622), palmitoyl-(protein) hydrolase activity (GO:0008474), lipase activity (GO:0016298), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear membrane (GO:0031965), extracellular exosome (GO:0070062), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Metabolism of nitric oxide: NOS3 activation and regulation	1
RAF/MAP kinase cascade	1
Metabolism	1
MAPK1/MAPK3 signaling	1
Signal Transduction	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular membrane-bounded organelle	3
protein deacylation	1
lipoprotein catabolic process	1
macromolecule depalmitoylation	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
lipid transport	1
monocarboxylic acid transport	1
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
negative regulation of protein transport	1
negative regulation of protein localization to plasma membrane	1
negative regulation of macroautophagy	1
aggrephagy	1
regulation of aggrephagy	1
primary metabolic process	1
macroautophagy	1
protein targeting to vacuole	1
autophagy	1
macromolecule deacylation	1
phospholipase activity	1
lysophospholipase A1 activity	1
thiolester hydrolase activity	1
palmitoyl hydrolase activity	1
catalytic activity, acting on a protein	1
hydrolase activity, acting on ester bonds	1
binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
membrane	1
cell periphery	1
nucleus	1
nuclear envelope	1
organelle membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

1634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPLA1	ESPL1	Q14674	783
LYPLA1	INCENP	Q9NQS7	767
LYPLA1	CDC14A	Q9UNH5	717
LYPLA1	GNA13	Q14344	669
LYPLA1	AURKB	Q96GD4	660
LYPLA1	PPT1	P50897	656
LYPLA1	ZW10	O43264	641
LYPLA1	ABHD17A	Q96GS6	623
LYPLA1	MOV10	Q9HCE1	615
LYPLA1	LIMK1	P53667	603
LYPLA1	ABHD13	Q7L211	588
LYPLA1	ZWINT	O95229	548
LYPLA1	PTTG1	O95997	544
LYPLA1	PPT2	Q9UMR5	544
LYPLA1	ABHD11	Q8NFV4	530

IntAct

42 interactions, top by confidence:

A	B	Type	Score
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
LYPLA1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
LYPLA1	SFMBT2	psi-mi:“MI:0915”(physical association)	0.560
NS	LYPLA1	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
PRSS35	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
TRIM11	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
CAMK2A	SMCHD1	psi-mi:“MI:0914”(association)	0.350
MTRF1	MEIS1	psi-mi:“MI:0914”(association)	0.350
GSX1	YKT6	psi-mi:“MI:0914”(association)	0.350
BEX4	KLHL41	psi-mi:“MI:0914”(association)	0.350
LIN37	LYPLA1	psi-mi:“MI:0914”(association)	0.350
CTSO	LYPLA1	psi-mi:“MI:0914”(association)	0.350
GUCA1B	LYPLA1	psi-mi:“MI:0914”(association)	0.350
HOXD11	LYPLA1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
CAMK2A	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
AQP3	UBXN8	psi-mi:“MI:0914”(association)	0.350
MRPS2	POLRMT	psi-mi:“MI:0914”(association)	0.350
ARHGEF16	GAPDHS	psi-mi:“MI:0914”(association)	0.350
AIFM1	HSPA12A	psi-mi:“MI:0914”(association)	0.350
TRIM11	LYPLA1	psi-mi:“MI:0914”(association)	0.350
CAMK2A	MAP3K7	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
VCAM1		psi-mi:“MI:0914”(association)	0.350

BioGRID (77): LYPLA1 (Two-hybrid), LYPLA1 (Affinity Capture-MS), LYPLA1 (Affinity Capture-MS), APRT (Co-fractionation), ASNS (Co-fractionation), DPYSL2 (Co-fractionation), LYPLA1 (Co-fractionation), LYPLA1 (Co-fractionation), LYPLA1 (Co-fractionation), LYPLA1 (Co-fractionation), LYPLA1 (Co-fractionation), PRDX6 (Co-fractionation), TTC38 (Co-fractionation), LYPLA1 (Affinity Capture-MS), LYPLA1 (Affinity Capture-MS)

ESM2 similar proteins: A5A6K8, A5A6N7, B4G0F3, O35678, O75608, O77821, P00341, P07687, P15246, P16125, P17174, P22061, P22062, P33571, P42123, P70470, P79381, P80895, P97823, Q0V9A9, Q3MHR0, Q3UFF7, Q42539, Q42563, Q4I8Q4, Q4R5H0, Q53H82, Q5RA89, Q5RBR7, Q5RBU3, Q5XGR8, Q6AV34, Q6P7K0, Q7TP52, Q7TSV4, Q84WK4, Q8GWU0, Q8GYK2, Q8R1G2, Q92047

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1600 predictions. Top by Δscore:

Variant	Effect	Δscore
8:54055134:C:CC	acceptor_gain	1.0000
8:54062246:GTACT:G	donor_loss	1.0000
8:54062247:TACTT:T	donor_loss	1.0000
8:54062248:ACT:A	donor_loss	1.0000
8:54062249:CTTAC:C	donor_loss	1.0000
8:54062250:TT:T	donor_loss	1.0000
8:54062252:A:AC	donor_gain	1.0000
8:54062252:A:C	donor_loss	1.0000
8:54062253:C:CG	donor_gain	1.0000
8:54062253:CT:C	donor_gain	1.0000
8:54062253:CTA:C	donor_gain	1.0000
8:54062253:CTAT:C	donor_gain	1.0000
8:54062253:CTATT:C	donor_gain	1.0000
8:54062325:C:CA	acceptor_loss	1.0000
8:54062326:T:C	acceptor_loss	1.0000
8:54063322:A:AC	donor_gain	1.0000
8:54063323:C:CC	donor_gain	1.0000
8:54063324:TTACC:T	donor_loss	1.0000
8:54063325:TA:T	donor_loss	1.0000
8:54063326:A:AC	donor_gain	1.0000
8:54063326:A:C	donor_loss	1.0000
8:54063326:AC:A	donor_gain	1.0000
8:54063327:C:CA	donor_gain	1.0000
8:54063327:CC:C	donor_gain	1.0000
8:54063371:CAGGC:C	acceptor_gain	1.0000
8:54063373:GGC:G	acceptor_gain	1.0000
8:54063374:GC:G	acceptor_gain	1.0000
8:54063375:CC:C	acceptor_gain	1.0000
8:54063376:C:CC	acceptor_gain	1.0000
8:54063376:CTA:C	acceptor_loss	1.0000

AlphaMissense

1504 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:54055066:A:C	F118L	0.999
8:54055066:A:T	F118L	0.999
8:54055068:A:G	F118L	0.999
8:54062321:A:C	F73L	0.999
8:54062321:A:T	F73L	0.999
8:54062323:A:G	F73L	0.999
8:54063329:A:G	W72R	0.998
8:54063329:A:T	W72R	0.998
8:54052755:C:A	G121V	0.997
8:54052755:C:T	G121E	0.997
8:54055067:A:G	F118S	0.997
8:54055070:C:T	G117E	0.997
8:54062324:C:A	W72C	0.997
8:54062324:C:G	W72C	0.997
8:54051130:T:A	D174V	0.996
8:54051139:C:A	G171V	0.996
8:54051139:C:T	G171E	0.996
8:54052685:G:C	C144W	0.996
8:54052756:C:G	G121R	0.996
8:54052756:C:T	G121R	0.996
8:54055065:A:G	S119P	0.996
8:54063361:A:T	V61D	0.996
8:54065806:A:G	W37R	0.996
8:54065806:A:T	W37R	0.996
8:54051027:G:C	H208Q	0.995
8:54051027:G:T	H208Q	0.995
8:54052688:A:C	S143R	0.995
8:54052688:A:T	S143R	0.995
8:54052690:T:G	S143R	0.995
8:54055060:C:A	Q120H	0.995

dbSNP variants (sampled 300 via entrez): RS1000059847 (8:54072875 G>T), RS1000111910 (8:54073104 T>A,C), RS1000124359 (8:54066152 T>C), RS1000139836 (8:54046336 G>A), RS1000177438 (8:54066398 A>G), RS1000219029 (8:54096888 G>C,T), RS1000349396 (8:54099504 T>C,G), RS1000390722 (8:54093710 A>G), RS1000426172 (8:54099764 G>C), RS1000489413 (8:54045917 T>C), RS1000528146 (8:54066486 G>T), RS1000545709 (8:54103909 T>C), RS1000562902 (8:54089496 G>C,T), RS1000614313 (8:54058652 T>C), RS1000626040 (8:54061968 G>A)

Disease associations

OMIM: gene MIM:605599 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003225_11	Pelvic organ prolapse (moderate/severe)	7.000000e-06
GCST003255_6	Urinary albumin-to-creatinine ratio	6.000000e-07
GCST004505_74	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	9.000000e-31
GCST004507_1	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	8.000000e-22
GCST004508_14	Waist-to-hip ratio adjusted for BMI in non-smokers	3.000000e-22
GCST004862_150	Itch intensity from mosquito bite adjusted by bite size	1.000000e-07
GCST004862_7	Itch intensity from mosquito bite adjusted by bite size	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004318	smoking behavior
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1681631 (SINGLE PROTEIN), CHEMBL4680048 (PROTEIN FAMILY)

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
Palmostatin B	Inhibition	8.27	pIC50
ML211	Inhibition	7.77	pIC50
ML348	Inhibition	6.52	pKi

Binding affinities (BindingDB)

1 measured of 19 human assays (20 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
ML349	KI	180 nM

ChEMBL bioactivities

18 potent at pChembl≥5 of 18 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.33	Kd	0.466	nM	CHEMBL5653589
9.33	ED50	0.466	nM	CHEMBL5653589
8.60	IC50	2.5	nM	CHEMBL3133031
8.60	IC50	2.5	nM	CHEMBL5568560
8.36	IC50	4.4	nM	CHEMBL5565391
8.27	IC50	5.4	nM	PALMOSTATIN B
8.22	IC50	6	nM	CHEMBL5562679
7.97	IC50	10.6	nM	CHEMBL5565657
7.77	IC50	17	nM	CHEMBL1903566
7.57	IC50	27	nM	CHEMBL3133034
6.83	IC50	148	nM	CHEMBL3133035
6.55	Ki	280	nM	CHEMBL600764
6.52	Ki	300	nM	CHEMBL600764
6.17	IC50	670	nM	PALMOSTATIN B
6.00	Ki	990	nM	CHEMBL3133032

PubChem BioAssay actives

39 with measured affinity, of 59 total; 26 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148677: Binding affinity to human LYPLA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0005	uM
(3S,4S)-4-decyl-3-[4-[3-(dimethylamino)propylsulfonyl]butyl]oxetan-2-one	2084118: Inhibition of APT1 (unknown origin)	ic50	0.0025	uM
(3S,4S)-3-decyl-4-[4-[3-(dimethylamino)propylsulfonyl]butyl]oxetan-2-one	1079563: Inhibition of APT1 (unknown origin)	ic50	0.0025	uM
(3S,4S)-4-dec-9-ynyl-3-[4-[3-(dimethylamino)propylsulfonyl]butyl]oxetan-2-one	2084118: Inhibition of APT1 (unknown origin)	ic50	0.0044	uM
(3S,4S)-3-decyl-4-[2-(3,4-dimethoxyphenyl)ethyl]oxetan-2-one	1079563: Inhibition of APT1 (unknown origin)	ic50	0.0054	uM
(3S,4S)-3-dec-9-ynyl-4-[2-(3,4-dimethoxyphenyl)ethyl]oxetan-2-one	2084118: Inhibition of APT1 (unknown origin)	ic50	0.0060	uM
(3S,4S)-4-decyl-3-[4-[3-[methyl(pent-4-ynyl)amino]propylsulfonyl]butyl]oxetan-2-one	2084118: Inhibition of APT1 (unknown origin)	ic50	0.0106	uM
(4-tert-butylpiperidin-1-yl)-[4-[hydroxy(diphenyl)methyl]triazol-2-yl]methanone	1079558: Inhibition of human APT1	ic50	0.0170	uM
methyl (2R)-2-[[(6aS,8S)-5-(2-aminoethyl)-8-(hexadecylsulfonylamino)-6,11-dioxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepine-2-carbonyl]amino]-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylpropanoate	1079563: Inhibition of APT1 (unknown origin)	ic50	0.0270	uM
[4-[hydroxy(diphenyl)methyl]triazol-2-yl]-piperidin-1-ylmethanone	1079558: Inhibition of human APT1	ic50	0.0300	uM
tert-butyl (6aS,8S)-5-(2-aminoethyl)-8-(hexadecylsulfonylamino)-6,11-dioxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepine-2-carboxylate	1079563: Inhibition of APT1 (unknown origin)	ic50	0.1480	uM
(5,5-dioxo-4H-thieno[3,2-c]thiochromen-2-yl)-[4-(4-methoxyphenyl)piperazin-1-yl]methanone	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	0.1800	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	0.2800	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	0.5100	uM
2-[[4-[[4-[2-(dimethylamino)ethoxy-phenylboranyl]phenyl]methoxymethyl]phenyl]-phenylboranyl]oxy-N,N-dimethylethanamine	1079561: Inhibition of APT1 (unknown origin) by enzyme kinetic assay	ki	0.9900	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	1.1000	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	1.4000	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	2.3000	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	2.6000	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	2.7000	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	3.2000	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	3.2000	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	3.7000	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	3.9000	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	4.6000	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	6.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases expression, affects methylation, increases abundance	2
Rotenone	decreases expression, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
methylselenic acid	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases expression, increases abundance	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1676101	Binding	Inhibition of APT1	Small molecule inhibition of protein depalmitoylation as a new approach towards downregulation of oncogenic Ras signalling. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3AE	Abcam HEK293T LYPLA1 KO	Transformed cell line	Female
CVCL_SW10	HAP1 LYPLA1 (-) 1	Cancer cell line	Male
CVCL_SW11	HAP1 LYPLA1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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