LYPLAL1

Summary

LYPLAL1 (lysophospholipase like 1, HGNC:20440) is a protein-coding gene on chromosome 1q41, encoding Lysophospholipase-like protein 1 (Q5VWZ2). Palmitoyl thioesterase that catalyzes depalmitoylation of CGAS and KCNMA1.

Enables palmitoyl-(protein) hydrolase activity. Involved in negative regulation of cGAS/STING signaling pathway. Located in cytosol.

Source: NCBI Gene 127018 — RefSeq curated summary.

At a glance

• GWAS associations: 96
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• MANE Select transcript: NM_138794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20440
Approved symbol	LYPLAL1
Name	lysophospholipase like 1
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	Q96AV0
Ensembl gene	ENSG00000143353
Ensembl biotype	protein_coding
OMIM	616548
Entrez	127018

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding_CDS_not_defined, 9 protein_coding

ENST00000366927, ENST00000366928, ENST00000460522, ENST00000463964, ENST00000469590, ENST00000474379, ENST00000475724, ENST00000477938, ENST00000478794, ENST00000481007, ENST00000483635, ENST00000496776, ENST00000910158, ENST00000910159, ENST00000910160, ENST00000910161, ENST00000910162, ENST00000910163, ENST00000917492

RefSeq mRNA: 7 — MANE Select: NM_138794 NM_001300769, NM_001300770, NM_001300771, NM_001300772, NM_001350628, NM_001350629, NM_138794

CCDS: CCDS1522, CCDS73032

Canonical transcript exons

ENST00000366928 — 5 exons

Exon	Start	End
ENSE00001443008	219173878	219173981
ENSE00003491457	219210532	219210647
ENSE00003533244	219179147	219179246
ENSE00003568517	219193082	219193251
ENSE00003846304	219211492	219212858

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.3354 / max 489.7264, expressed in 1805 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8629	39.2321	1803
8630	1.8172	830
8631	0.9130	260
8632	0.3731	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.89	gold quality
left ventricle myocardium	UBERON:0006566	98.50	gold quality
calcaneal tendon	UBERON:0003701	97.25	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.86	gold quality
myocardium	UBERON:0002349	96.55	gold quality
adrenal tissue	UBERON:0018303	95.74	gold quality
pigmented layer of retina	UBERON:0001782	95.51	gold quality
metanephros cortex	UBERON:0010533	95.47	gold quality
right adrenal gland cortex	UBERON:0035827	95.46	gold quality
right adrenal gland	UBERON:0001233	95.36	gold quality
oocyte	CL:0000023	95.33	gold quality
body of pancreas	UBERON:0001150	95.32	gold quality
heart right ventricle	UBERON:0002080	95.18	gold quality
upper arm skin	UBERON:0004263	95.13	gold quality
cortex of kidney	UBERON:0001225	94.91	gold quality
biceps brachii	UBERON:0001507	94.79	gold quality
left adrenal gland	UBERON:0001234	94.60	gold quality
adult mammalian kidney	UBERON:0000082	94.59	gold quality
tendon	UBERON:0000043	94.33	gold quality
left adrenal gland cortex	UBERON:0035825	94.28	gold quality
adrenal cortex	UBERON:0001235	94.26	gold quality
kidney	UBERON:0002113	94.17	gold quality
metanephros	UBERON:0000081	94.15	gold quality
adrenal gland	UBERON:0002369	94.08	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.02	gold quality
renal medulla	UBERON:0000362	94.01	gold quality
deltoid	UBERON:0001476	93.83	gold quality
corpus callosum	UBERON:0002336	93.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.65	gold quality
upper leg skin	UBERON:0004262	93.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

73 targeting LYPLAL1, 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-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-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-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 13)

• TFAP2B, LYPLAL1 and MSRA are associated with adiposity and fat distribution. (PMID:19557161)
• central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B (PMID:21674055)
• genetic association studies in Danish population: Quantitative metabolic phenotypes in obesity are associated with SNP in various genes: LYPLAL1 (rs4846567) is associated with waist-hip ratio and insulin sensitivity in women. (PMID:21953277)
• LYPLAL1 exhibits neither phospholipase nor triacylglycerol lipase activity, but rather accepts short-chain substrates (PMID:22052940)
• Gene-treatment interactions were observed for short-term weight loss. (LYPLAL1 rs2605100, Plifestyle*SNP = 0.032) (PMID:22179955)
• Our results suggest that LYPLAL1 rs4846567 and NISCH rs6784615 may influence fat distribution in the Japanese population. (PMID:23221025)
• Data provide evidence that variants of MC4R and LYPLAL1 modulate body fat distribution with sexual dimorphism in a Chinese population. (PMID:26848030)
• The LYPLAL1 genotype is associated with differences in eating behavior and loss of extensive body weight following Roux-en-Y gastric bypass (RYGB) surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB-associated therapy success. (PMID:27181159)
• Among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. (PMID:27752939)
• Novel LYPLAL1 SNP rs2605100 is associated with childhood hypertension adjusted by obesity. (PMID:28645872)
• Metabolic effects of LYPLAL1 rs12137855-C were similar, but statistically less robust, to the effects of GCKR rs1260326-T. TM6SF2 rs58542926-T displayed opposite metabolic effects when compared with the fatty liver associations. (PMID:29648650)
• ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation. (PMID:37676718)
• Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy. (PMID:37802025)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lyplal1	ENSDARG00000088764
mus_musculus	Lyplal1	ENSMUSG00000039246
rattus_norvegicus	Lyplal1	ENSRNOG00000023130
drosophila_melanogaster	CG6567	FBGN0037842
caenorhabditis_elegans	ath-1	WBGENE00010564

Paralogs (2): LYPLA2 (ENSG00000011009), LYPLA1 (ENSG00000120992)

Protein

Protein identifiers

Lysophospholipase-like protein 1 — Q5VWZ2 (reviewed: Q5VWZ2)

All UniProt accessions (1): Q5VWZ2

UniProt curated annotations — full annotation on UniProt →

Function. Palmitoyl thioesterase that catalyzes depalmitoylation of CGAS and KCNMA1. Acts as a regulator of innate immunity by mediating depalmitoylation of CGAS, thereby preventing CGAS homodimerization and cyclic GMP-AMP synthase activity. Does not exhibit phospholipase nor triacylglycerol lipase activity, able to hydrolyze only short chain substrates due to its shallow active site.

Subcellular location. Cytoplasm. Cytosol Cytoplasm. Cytosol.

Miscellaneous. May be due to a competing acceptor splice site.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VWZ2-1	1	yes
Q5VWZ2-2	2

RefSeq proteins (7): NP_001287698, NP_001287699, NP_001287700, NP_001287701, NP_001337557, NP_001337558, NP_620149* (*=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), 1 shown:

• S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+) (RHEA:19233)

UniProt features (31 total): strand 11, helix 8, active site 3, mutagenesis site 2, sequence variant 2, initiator methionine 1, chain 1, sequence conflict 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3U0V	X-RAY DIFFRACTION	1.72
5KRE	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VWZ2-F1	95.84	0.95

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): 124 (charge relay system); 179 (charge relay system); 211 (charge relay system)

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
211	abolished palmitoyl thioesterase activity; when associated with a-179.
179	abolished palmitoyl thioesterase activity; when associated with a-211.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_DEACYLATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION

GO Biological Process (4): negative regulation of Golgi to plasma membrane protein transport (GO:0042997), negative regulation of cGAS/STING signaling pathway (GO:0160049), macromolecule depalmitoylation (GO:0098734), cGAS/STING signaling pathway (GO:0140896)

GO Molecular Function (5): phosphatidylcholine lysophospholipase A1 activity (GO:0004622), palmitoyl-(protein) hydrolase activity (GO:0008474), hydrolase activity, acting on ester bonds (GO:0016788), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
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 cytoplasmic pattern recognition receptor signaling pathway	1
cGAS/STING signaling pathway	1
macromolecule deacylation	1
cytoplasmic pattern recognition receptor signaling pathway	1
lysophospholipase A1 activity	1
thiolester hydrolase activity	1
palmitoyl hydrolase activity	1
catalytic activity, acting on a protein	1
hydrolase activity	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPLAL1	PPP1R3B	Q86XI6	790
LYPLAL1	PNPLA3	Q9NST1	770
LYPLAL1	TM6SF2	Q9BZW4	722
LYPLAL1	NCAN	O14594	696
LYPLAL1	GCKR	Q14397	666
LYPLAL1	GRB14	Q14449	643
LYPLAL1	MBOAT7	Q96N66	620
LYPLAL1	COBLL1	Q53SF7	613
LYPLAL1	ABHD17A	Q96GS6	584
LYPLAL1	ARL15	Q9NXU5	581
LYPLAL1	GNPDA2	Q8TDQ7	575
LYPLAL1	TFAP2B	Q92481	567
LYPLAL1	SAMM50	Q9Y512	561
LYPLAL1	ABHD17C	Q6PCB6	545
LYPLAL1	TMEM18	Q96B42	540

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
LYPLAL1	CT55	psi-mi:“MI:0915”(physical association)	0.560
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
LYPLAL1	E7	psi-mi:“MI:0915”(physical association)	0.370
LRRK2		psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
PRTN3	MANBA	psi-mi:“MI:0914”(association)	0.350
RAMP3	MGST3	psi-mi:“MI:0914”(association)	0.350
CTDSP1	XPO1	psi-mi:“MI:0914”(association)	0.350
CD300E	RAP1B	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
C1QA	VWA8	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CELA3A	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
CHIA	SLC25A16	psi-mi:“MI:0914”(association)	0.350
KLK1	PPOX	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350
NME3	VWA8	psi-mi:“MI:0914”(association)	0.350
NXPH3	NXPH4	psi-mi:“MI:0914”(association)	0.350
OSTM1	ASMTL	psi-mi:“MI:0914”(association)	0.350
RAMP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
SETD6	GFPT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): LYPLAL1 (Proximity Label-MS), LYPLAL1 (Proximity Label-MS), LYPLAL1 (Proximity Label-MS), LYPLAL1 (Proximity Label-MS), LYPLAL1 (Proximity Label-MS), LYPLAL1 (Co-fractionation), LYPLAL1 (Co-fractionation), LYPLAL1 (Co-fractionation), SUMF2 (Co-fractionation), LYPLAL1 (Co-fractionation), LYPLAL1 (Co-fractionation), LYPLAL1 (Co-fractionation), LYPLAL1 (Co-fractionation), SH3BGRL3 (Co-fractionation), PTRHD1 (Co-fractionation)

ESM2 similar proteins: A0A3L7I2I8, O35678, O60733, P11172, P13439, P37287, P97570, P97819, Q08C93, Q0V8R7, Q3TY86, Q3U1V6, Q3UFF7, Q3ZCH9, Q4JIJ2, Q5E9H9, Q5F477, Q5IH13, Q5R514, Q5R8C2, Q5RBU3, Q5REX5, Q5VWZ2, Q5XH09, Q62878, Q64323, Q6DHV7, Q6DJF8, Q6GM82, Q6P7K0, Q6PE15, Q7TP52, Q80SY6, Q86TI2, Q86WA6, Q8AYC9, Q8BGT5, Q8BVG4, Q8JGT5, Q8R164

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1063 predictions. Top by Δscore:

Variant	Effect	Δscore
1:219193251:GGTAA:G	donor_loss	1.0000
1:219193252:G:GC	donor_loss	1.0000
1:219193252:G:GG	donor_gain	1.0000
1:219210528:TTAG:T	acceptor_loss	1.0000
1:219210530:AGG:A	acceptor_loss	1.0000
1:219210531:G:GT	acceptor_loss	1.0000
1:219210531:GGA:G	acceptor_gain	1.0000
1:219210645:CAGG:C	donor_loss	1.0000
1:219210648:G:GG	donor_gain	1.0000
1:219210648:GTA:G	donor_loss	1.0000
1:219210649:T:A	donor_loss	1.0000
1:219211490:A:AG	acceptor_gain	1.0000
1:219211491:G:GG	acceptor_gain	1.0000
1:219173944:G:T	donor_gain	0.9900
1:219193058:T:A	acceptor_gain	0.9900
1:219193059:G:A	acceptor_gain	0.9900
1:219193249:TAG:T	donor_gain	0.9900
1:219210530:A:AG	acceptor_gain	0.9900
1:219210530:AGGAG:A	acceptor_gain	0.9900
1:219210531:G:GG	acceptor_gain	0.9900
1:219210531:GGAGG:G	acceptor_gain	0.9900
1:219211486:CTCTA:C	acceptor_loss	0.9900
1:219211487:TCTAG:T	acceptor_loss	0.9900
1:219211488:CTAGG:C	acceptor_loss	0.9900
1:219211489:TA:T	acceptor_loss	0.9900
1:219211490:A:AC	acceptor_loss	0.9900
1:219173943:G:GT	donor_gain	0.9800
1:219193069:G:A	acceptor_gain	0.9800
1:219206802:G:GT	donor_gain	0.9800
1:219210514:GTAT:G	acceptor_gain	0.9800

AlphaMissense

1554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:219193119:T:A	W77R	0.996
1:219193119:T:C	W77R	0.996
1:219210537:T:C	F123L	0.995
1:219210539:C:A	F123L	0.995
1:219210539:C:G	F123L	0.995
1:219193122:T:C	F78L	0.994
1:219193124:T:A	F78L	0.994
1:219193124:T:G	F78L	0.994
1:219210615:A:C	S149R	0.994
1:219210617:T:A	S149R	0.994
1:219210617:T:G	S149R	0.994
1:219210618:T:C	F150L	0.994
1:219210620:T:A	F150L	0.994
1:219210620:T:G	F150L	0.994
1:219210540:T:C	S124P	0.993
1:219193121:G:C	W77C	0.991
1:219193121:G:T	W77C	0.991
1:219211549:G:C	D179H	0.991
1:219211550:A:T	D179V	0.991
1:219179237:C:A	A61D	0.988
1:219210547:G:T	G126V	0.987
1:219210545:G:A	M125I	0.986
1:219210545:G:C	M125I	0.986
1:219210545:G:T	M125I	0.986
1:219210532:G:A	G121E	0.985
1:219211550:A:C	D179A	0.985
1:219210535:G:A	G122E	0.983
1:219210538:T:C	F123S	0.983
1:219210541:C:A	S124Y	0.983
1:219210547:G:A	G126E	0.983

dbSNP variants (sampled 300 via entrez): RS1000007334 (1:219378388 A>G,T), RS1000008434 (1:219420015 C>T), RS1000026533 (1:219293693 A>G), RS1000037145 (1:219378662 A>G), RS1000046169 (1:219293223 T>G), RS1000052663 (1:219394631 C>A), RS1000064757 (1:219180745 T>G), RS1000065442 (1:219334925 T>A), RS1000076366 (1:219351302 A>G), RS1000077310 (1:219293414 T>A), RS1000078151 (1:219418732 A>C,G), RS1000087820 (1:219174352 C>A,G,T), RS1000115314 (1:219308414 T>C), RS1000126257 (1:219240195 G>A), RS1000137204 (1:219333379 C>T)

Disease associations

OMIM: gene MIM:616548 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

96 associations (top):

Study	Trait	p-value
GCST000428_1	Adiposity	3.000000e-08
GCST000817_163	Height	2.000000e-12
GCST000829_4	Waist-hip ratio	7.000000e-21
GCST001463_6	Adiponectin levels	5.000000e-07
GCST001465_2	Adiponectin levels	4.000000e-08
GCST001524_19	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-09
GCST001524_42	Visceral adipose tissue/subcutaneous adipose tissue ratio	2.000000e-06
GCST001526_11	Fasting blood insulin (BMI interaction)	2.000000e-08
GCST001954_3	Waist-hip ratio	7.000000e-09
GCST001956_85	Height	3.000000e-08
GCST002063_9	Sexual dimorphism in anthropometric traits	7.000000e-16
GCST002352_61	Type 2 diabetes	2.000000e-06
GCST002782_6	Waist-to-hip ratio adjusted for body mass index	6.000000e-35
GCST002782_7	Waist-to-hip ratio adjusted for body mass index	5.000000e-21
GCST002782_8	Waist-to-hip ratio adjusted for body mass index	3.000000e-35
GCST002782_9	Waist-to-hip ratio adjusted for body mass index	5.000000e-20
GCST003338_6	Waist-to-hip ratio adjusted for body mass index	8.000000e-07
GCST003972_2	Visceral adipose tissue/subcutaneous adipose tissue ratio	2.000000e-08
GCST003973_3	Visceral adipose tissue/subcutaneous adipose tissue ratio adjusted for BMI	3.000000e-08
GCST003999_5	Nose size	2.000000e-10
GCST004063_19	Waist circumference adjusted for body mass index	2.000000e-08
GCST004064_15	Waist-hip ratio	4.000000e-25
GCST004064_62	Waist-hip ratio	5.000000e-11
GCST004066_108	Hip circumference	2.000000e-15
GCST004066_56	Hip circumference	9.000000e-06
GCST004066_67	Hip circumference	5.000000e-18
GCST004500_60	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	7.000000e-07
GCST004501_110	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004505_75	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	4.000000e-16
GCST004505_76	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	7.000000e-28

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0004502	adiponectin measurement
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004340	body mass index
EFO:0005951	sexual dimorphism
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009180	rosacea severity measurement
EFO:0008343	sex interaction measurement
EFO:0008007	age at assessment
EFO:0004847	age at onset
EFO:0009959	diverticular disease
EFO:0004713	FEV/FVC ratio
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0007800	body fat percentage
EFO:0004530	triglyceride measurement
EFO:0007874	gut microbiome measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189133 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

3 measured of 12 human assays (12 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(R)-(2-phenylpiperidin-1-yl)(3-(4-(pyridin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methanone (5)	IC50	5 nM
(R)-(3-(4-(2-morpholinopyrimidin-5-yl)phenyl)-1H-1,2,4-triazol-1-yl)(2-phenylpiperidin-1-yl)methanone (6)	IC50	5 nM
(R)-4’-(1-(2-phenylpiperidine-1-carbonyl)-1H-1,2,4-triazol-3-yl)-[1,1’-biphenyl]-4-sulfonamide (4)	IC50	7 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.31	EC50	490	nM	CHEMBL5403181

PubChem BioAssay actives

12 with measured affinity, of 14 total; 12 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
(2R,3R)-2-(3-ethynylphenyl)-1-[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazole-1-carbonyl]piperidine-3-carboxylic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0050	uM
(2R,3R)-1-[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazole-1-carbonyl]-2-phenylpiperidine-3-carboxylic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0060	uM
[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazol-1-yl]-[(2R)-2-phenylpiperidin-1-yl]methanone	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0070	uM
(2R,4R)-1-[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazole-1-carbonyl]-2-phenylpiperidine-4-carboxylic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0110	uM
N,N-dimethyl-4-[4-[2-[(2R)-2-phenylpiperidine-1-carbonyl]triazol-4-yl]phenyl]benzenesulfonamide	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0210	uM
[(2R)-2-phenylpiperidin-1-yl]-[3-(4-pyridin-3-ylphenyl)-1,2,4-triazol-1-yl]methanone	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0360	uM
N,N-dimethyl-4-[4-[1-[(2R)-2-phenylpiperidine-1-carbonyl]-1,2,4-triazol-3-yl]phenyl]benzenesulfonamide	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0480	uM
4-[4-[2-[(2R)-2-phenylpiperidine-1-carbonyl]triazol-4-yl]phenyl]benzoic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0590	uM
5-[(4-chlorophenyl)methylsulfanyl]-2-(2,3-dihydro-1-benzofuran-5-ylsulfonyl)-1,2,4-triazol-3-amine	2022480: Activation of 6XHis-FP-rhodamine-tagged full-length human LYPLAL1 expressed in Escherichia coli BL21(DE3) cells preincubated for 60 mins followed by FP-rhodamine probe addition for 30 mins	ec50	0.4900	uM
1-[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazole-1-carbonyl]-2-phenylpiperidine-4-carboxylic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.7100	uM
(2S,3S)-1-[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazole-1-carbonyl]-2-phenylpiperidine-3-carboxylic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	1.1000	uM
(2S,4S)-1-[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazole-1-carbonyl]-2-phenylpiperidine-4-carboxylic acid	1801981: Gel-based ABPP (LYPLAL1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	6.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	5
sodium arsenite	increases abundance, increases expression	2
Cisplatin	affects expression, decreases expression	2
Nickel	decreases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
Quercetin	decreases expression	1
Testosterone	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209096	Binding	Inhibition of LYPLAL1 binding to FP-biotin in [12C][14N]-lysine, arginine and [13C6][15N2]-lysine, arginine labeled HEK293T cells at 20 uM after 1 hr by isotopic activity-based protein profiling-MudPIT assay	Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SW14	HAP1 LYPLAL1 (-) 1	Cancer cell line	Male
CVCL_SW15	HAP1 LYPLAL1 (-) 2	Cancer cell line	Male
CVCL_SW16	HAP1 LYPLAL1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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