LPCAT3

Summary

LPCAT3 (lysophosphatidylcholine acyltransferase 3, HGNC:30244) is a protein-coding gene on chromosome 12p13.31, encoding Lysophospholipid acyltransferase 5 (Q6P1A2). Lysophospholipid O-acyltransferase (LPLAT) that catalyzes the reacylation step of the phospholipid remodeling process also known as the Lands cycle.

Enables 1-acylglycerophosphocholine O-acyltransferase activity; 1-acylglycerophosphoethanolamine O-acyltransferase activity; and 1-acylglycerophosphoserine O-acyltransferase activity. Involved in phosphatidylcholine acyl-chain remodeling; phosphatidylethanolamine acyl-chain remodeling; and phosphatidylserine acyl-chain remodeling. Located in endoplasmic reticulum membrane.

Source: NCBI Gene 10162 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 9 total
• Druggable target: yes
• MANE Select transcript: NM_005768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30244
Approved symbol	LPCAT3
Name	lysophosphatidylcholine acyltransferase 3
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	C3F, nessy, LPLAT12
Ensembl gene	ENSG00000111684
Ensembl biotype	protein_coding
OMIM	611950
Entrez	10162

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding, 5 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay, 2 retained_intron

ENST00000261407, ENST00000535021, ENST00000535479, ENST00000536797, ENST00000536971, ENST00000537179, ENST00000538910, ENST00000538987, ENST00000540060, ENST00000540090, ENST00000543794, ENST00000545459, ENST00000620843, ENST00000907763, ENST00000907764, ENST00000907765, ENST00000907766, ENST00000907767, ENST00000907768, ENST00000925113, ENST00000925114, ENST00000954703, ENST00000954704, ENST00000954705

RefSeq mRNA: 1 — MANE Select: NM_005768 NM_005768

CCDS: CCDS8572

Canonical transcript exons

ENST00000261407 — 13 exons

Exon	Start	End
ENSE00001213045	6977598	6977745
ENSE00001358489	7018274	7018476
ENSE00003468101	6982676	6982782
ENSE00003483318	6981811	6981904
ENSE00003491007	6978603	6978689
ENSE00003491532	6983432	6983539
ENSE00003528772	6977367	6977525
ENSE00003588886	6981004	6981182
ENSE00003601917	6981595	6981632
ENSE00003612895	6977134	6977262
ENSE00003639688	6979471	6979579
ENSE00003693826	6978341	6978507
ENSE00003843880	6976185	6976891

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5749 / max 1232.0319, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129226	25.7798	1809
129225	0.7951	381

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.50	gold quality
right adrenal gland	UBERON:0001233	95.49	gold quality
mucosa of transverse colon	UBERON:0004991	95.46	gold quality
body of stomach	UBERON:0001161	95.44	gold quality
rectum	UBERON:0001052	95.42	gold quality
left adrenal gland	UBERON:0001234	95.39	gold quality
right adrenal gland cortex	UBERON:0035827	95.39	gold quality
body of pancreas	UBERON:0001150	95.38	gold quality
left adrenal gland cortex	UBERON:0035825	95.26	gold quality
islet of Langerhans	UBERON:0000006	94.75	gold quality
upper lobe of left lung	UBERON:0008952	94.68	gold quality
metanephros cortex	UBERON:0010533	94.59	gold quality
adrenal cortex	UBERON:0001235	94.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.41	gold quality
transverse colon	UBERON:0001157	94.29	gold quality
stomach	UBERON:0000945	93.96	gold quality
upper lobe of lung	UBERON:0008948	93.86	gold quality
pancreas	UBERON:0001264	93.81	gold quality
adrenal gland	UBERON:0002369	93.69	gold quality
minor salivary gland	UBERON:0001830	93.56	gold quality
right lung	UBERON:0002167	93.56	gold quality
small intestine	UBERON:0002108	93.53	gold quality
duodenum	UBERON:0002114	93.41	gold quality
gastrocnemius	UBERON:0001388	92.75	gold quality
liver	UBERON:0002107	92.74	gold quality
left lobe of thyroid gland	UBERON:0001120	92.68	gold quality
right lobe of thyroid gland	UBERON:0001119	92.64	gold quality
mouth mucosa	UBERON:0003729	92.42	gold quality
skin of abdomen	UBERON:0001416	92.22	gold quality
omental fat pad	UBERON:0010414	92.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H3

miRNA regulators (miRDB)

87 targeting LPCAT3, 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-6870-5P	99.99	68.55	2115
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-548A-3P	99.76	70.58	3524

Literature-anchored findings (GeneRIF, showing 17)

• LPCAT3 is primarily responsible for hepatic LPCAT activity (PMID:18195019)
• MBOAT5 and MBOAT7 in arachidonate recycling, thus regulating free arachidonic acid levels and leukotriene synthesis in neutrophils (PMID:18772128)
• LPCAT3 is involved in phospholipids remodeling to achieve appropriate membrane lipid fatty acid composition. (PMID:18781350)
• These results indicate that human MBOAT5 is a lysophospholipid acyltransferase acting preferentially on lysophosphatidylcholine, lysophosphatidylserine and lysophosphatidylethanolamine. (PMID:18782225)
• characterization of LPCAT3; LPCAT3 expression in tissue culture increased phospholipids with relatively more saturated acyl chains; limiting LPCAT3 expression increased abundance of phospholipids with more unsaturated acyl chains (PMID:19351971)
• lysoPC acyltransferase 3 is a novel-signal-regulated enzyme that is centrally implicated in limiting free arachidonic acid levels in activated cells (PMID:20018618)
• Results establish for the first time that LPCAT3 is specifically regulated by LXRalpha. (PMID:20837115)
• LPCAT3 a key contributor to the human macrophages inflammatory response. (PMID:23580142)
• Our findings suggest that LPCAT3 plays an important role in M1/M2-macrophage polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders (PMID:25994902)
• findings identify LPCAT3 as a direct PPARdelta target gene and suggest a novel function of PPARdelta in regulation of phospholipid metabolism through LPCAT3. (PMID:27913621)
• Regulation of LPCAT3 expression might be associated with atherosclerotic progression in humans. (PMID:28683445)
• LPCAT3 is depleted in non-alcoholic steatohepatitis and leads to caspase-dependent/caspase-independent cell death. (PMID:30160786)
• Hyperuricemia induces lipid disturbances mediated by LPCAT3 upregulation in the liver. (PMID:32780898)
• The regulation of LPCAT3 by miR-124-3p.1 in acute kidney injury suppresses cell proliferation by disrupting phospholipid metabolism. (PMID:35286868)
• LPCAT3 Is Transcriptionally Regulated by YAP/ZEB/EP300 and Collaborates with ACSL4 and YAP to Determine Ferroptosis Sensitivity. (PMID:37166352)
• Methylation Regulation of LPCAT3 Improves Osteoarthritis by Regulating ACSL4 to Inhibit Chondrocyte Ferroptosis. (PMID:38073444)
• Inhibition of the MALT1-LPCAT3 axis protects cartilage degeneration and osteoarthritis. (PMID:38519981)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpcat3	ENSDARG00000075178
mus_musculus	Lpcat3	ENSMUSG00000004270
rattus_norvegicus	Lpcat3	ENSRNOG00000012269
drosophila_melanogaster	nes	FBGN0026630
caenorhabditis_elegans		WBGENE00020115

Paralogs (5): PORCN (ENSG00000102312), MBOAT7 (ENSG00000125505), MBOAT2 (ENSG00000143797), MBOAT1 (ENSG00000172197), MBOAT4 (ENSG00000177669)

Protein

Protein identifiers

Lysophospholipid acyltransferase 5 — Q6P1A2 (reviewed: Q6P1A2)

Alternative names: 1-acylglycerophosphocholine O-acyltransferase, 1-acylglycerophosphoethanolamine O-acyltransferase, 1-acylglycerophosphoserine O-acyltransferase, Lysophosphatidylcholine acyltransferase, Lysophosphatidylcholine acyltransferase 3, Lysophosphatidylserine acyltransferase, Membrane-bound O-acyltransferase domain-containing protein 5

All UniProt accessions (6): Q6P1A2, B7Z3N5, F5GYT3, F5H0M4, F5H680, F5H7K7

UniProt curated annotations — full annotation on UniProt →

Function. Lysophospholipid O-acyltransferase (LPLAT) that catalyzes the reacylation step of the phospholipid remodeling process also known as the Lands cycle. Catalyzes transfer of the fatty acyl chain from fatty acyl-CoA to 1-acyl lysophospholipid to form various classes of phospholipids. Converts 1-acyl lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) (LPCAT activity), 1-acyl lysophosphatidylserine (LPS) into phosphatidylserine (PS) (LPSAT activity) and 1-acyl lysophosphatidylethanolamine (LPE) into phosphatidylethanolamine (PE) (LPEAT activity). Favors polyunsaturated fatty acyl-CoAs as acyl donors compared to saturated fatty acyl-CoAs. Has higher activity for LPC acyl acceptors compared to LPEs and LPSs. Can also transfer the fatty acyl chain from fatty acyl-CoA to 1-O-alkyl lysophospholipid or 1-O-alkenyl lysophospholipid with lower efficiency. Acts as a major LPC O-acyltransferase in liver and intestine. As a component of the liver X receptor/NR1H3 or NR1H2 signaling pathway, mainly catalyzes the incorporation of arachidonate into PCs of endoplasmic reticulum (ER) membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles. Promotes processing of sterol regulatory protein SREBF1 in hepatocytes, likely by facilitating the translocation of SREBF1-SCAP complex from ER to the Golgi apparatus. Participates in mechanisms by which the liver X receptor/NR1H3 or NR1H2 signaling pathway counteracts lipid-induced ER stress response and inflammation. Down-regulates hepatic inflammation by limiting arachidonic acid availability for synthesis of inflammatory eicosanoids, such as prostaglandins. In enterocytes, acts as a component of a gut-brain feedback loop that coordinates dietary lipid absorption and food intake. Regulates the abundance of PCs containing linoleate and arachidonate in enterocyte membranes, enabling passive diffusion of fatty acids and cholesterol across the membrane for efficient chylomicron assembly. In the intestinal crypt, acts as a component of dietary-responsive phospholipid-cholesterol axis, regulating the biosynthesis of cholesterol and its mitogenic effects on intestinal stem cells.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in liver, pancreas and adipose tissue. Very low expression in skeletal muscle and heart. Detected in neutrophils.

Activity regulation. Activity is inhibited by thimerosal.

Domain organisation. The di-lysine motif confers endoplasmic reticulum localization.

Pathway. Lipid metabolism; phospholipid metabolism.

Similarity. Belongs to the membrane-bound acyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P1A2-1	1	yes
Q6P1A2-2	2

RefSeq proteins (1): NP_005759* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004299	MBOAT_fam	Family
IPR049941	LPLAT_7/PORCN-like	Family

Pfam: PF03062

Enzyme classification (BRENDA):

• EC 2.3.1.23 — 1-acylglycerophosphocholine O-acyltransferase (BRENDA: 25 organisms, 283 substrates, 101 inhibitors, 64 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
OLEOYL-COA	0.0004–0.152	15
1-ACYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0017–0.107	9
ARACHIDONOYL-COA	0.0032–0.7156	6
PALMITOYL-COA	0.0027–0.0413	4
STEAROYL-COA	0.0021–0.232	4
1-PALMITOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0018–0.0081	3
1-PALMITOYL-LYSOPHOSPHATIDYLCHOLINE	0.0023–0.7219	2
DOCOSAHEXANOYL-COA	0.0031–0.0132	2
LINOLEOYL-COA	0.0035–0.2014	2
LYSOPHOSPHATIDYLCHOLINE	0.0131–0.027	2
1-ACYL-2-LYSOPHOSPHATIDYLETHANOLAMINE	0.08	1
1-ACYL-SN-GLYCERO-3-PHOSPHOINOSITOL	0.0138	1
1-ALKENYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.092	1
ALPHA-LINOLENOYL-COA	0.214	1
ARACHIDONYL-COA	0.0005	1

Catalyzed reactions (Rhea), 12 shown:

• a 1-acyl-sn-glycero-3-phosphocholine + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphocholine + CoA (RHEA:12937)
• a 1-acyl-sn-glycero-3-phosphoethanolamine + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + CoA (RHEA:32995)
• a 1-acyl-sn-glycero-3-phospho-L-serine + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phospho-L-serine + CoA (RHEA:33191)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoyl-CoA = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + CoA (RHEA:35983)
• octadecanoyl-CoA + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine + CoA (RHEA:35987)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + CoA (RHEA:35991)
• (9Z,12Z)-octadecadienoyl-CoA + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + CoA (RHEA:35995)
• (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + CoA (RHEA:35999)
• 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + CoA (RHEA:36023)
• (9Z)-hexadecenoyl-CoA + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine + CoA (RHEA:37207)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + (9Z,12Z)-octadecadienoyl-CoA = 1-(9Z-octadecenoyl)-2-(9Z,12Z-octadienoyl)-sn-glycero-3-phospho-L-serine + CoA (RHEA:37375)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-L-serine + CoA (RHEA:37379)

UniProt features (19 total): transmembrane region 9, active site 2, sequence variant 2, initiator methionine 1, chain 1, short sequence motif 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1A2-F1	92.53	0.88

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 (2): 338; 374

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482801	Acyl chain remodelling of PS
R-HSA-1482839	Acyl chain remodelling of PE
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 293 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_PHOSPHATIDYLSERINE_ACYL_CHAIN_REMODELING, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_LIPID_MODIFICATION, GOBP_DIGESTION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, TGCGCANK_UNKNOWN, GOBP_INFLAMMATORY_RESPONSE, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, CMYB_01, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_DIGESTIVE_SYSTEM_PROCESS

GO Biological Process (18): phosphatidylcholine biosynthetic process (GO:0006656), lipid modification (GO:0030258), chylomicron assembly (GO:0034378), very-low-density lipoprotein particle assembly (GO:0034379), phosphatidylserine acyl-chain remodeling (GO:0036150), phosphatidylcholine acyl-chain remodeling (GO:0036151), phosphatidylethanolamine acyl-chain remodeling (GO:0036152), intestinal stem cell homeostasis (GO:0036335), regulation of cholesterol biosynthetic process (GO:0045540), positive regulation of intestinal cholesterol absorption (GO:0045797), negative regulation of inflammatory response (GO:0050728), endoplasmic reticulum membrane organization (GO:0090158), negative regulation of response to endoplasmic reticulum stress (GO:1903573), positive regulation of triglyceride transport (GO:1905885), lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644), phospholipid biosynthetic process (GO:0008654), regulation of plasma lipoprotein particle levels (GO:0097006)

GO Molecular Function (8): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), 2-acylglycerol-3-phosphate O-acyltransferase activity (GO:0047144), 1-acylglycerophosphocholine O-acyltransferase activity (GO:0047184), lysophospholipid acyltransferase activity (GO:0071617), 1-acylglycerophosphoethanolamine O-acyltransferase activity (GO:0106262), 1-acylglycerophosphoserine O-acyltransferase activity (GO:0106263), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	3
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acyltransferase activity, transferring groups other than amino-acyl groups	4
phosphatidylcholine metabolic process	3
lipid metabolic process	2
plasma lipoprotein particle assembly	2
lysophosphatidic acid acyltransferase activity	2
glycerophospholipid biosynthetic process	1
phosphatidylserine metabolic process	1
homeostasis of number of cells	1
cholesterol biosynthetic process	1
regulation of cholesterol metabolic process	1
regulation of sterol biosynthetic process	1
regulation of alcohol biosynthetic process	1
intestinal cholesterol absorption	1
regulation of intestinal cholesterol absorption	1
positive regulation of intestinal lipid absorption	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
endoplasmic reticulum organization	1
membrane organization	1
response to endoplasmic reticulum stress	1
negative regulation of cellular process	1
negative regulation of response to stimulus	1
regulation of response to endoplasmic reticulum stress	1
triglyceride transport	1
positive regulation of acylglycerol transport	1
regulation of triglyceride transport	1
primary metabolic process	1
organophosphate metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
regulation of biological process	1
acylglycerol O-acyltransferase activity	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPCAT3	ACSL4	O60488	823
LPCAT3	NCAPH2	Q6IBW4	796
LPCAT3	LPCAT1	Q8NF37	741
LPCAT3	GPX4	P36969	725
LPCAT3	LPCAT2	Q7L5N7	715
LPCAT3	AIFM2	Q9BRQ8	664
LPCAT3	LPCAT4	Q643R3	649
LPCAT3	ACSL3	O95573	612
LPCAT3	NCOA4	Q13772	603
LPCAT3	ALOX15	P16050	594
LPCAT3	SAT1	P21673	593
LPCAT3	EMG1	Q92979	583
LPCAT3	CHPT1	Q8WUD6	576
LPCAT3	C3	P01024	575
LPCAT3	SLC7A11	Q9UPY5	575

IntAct

88 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TACR1	ATP5PB	psi-mi:“MI:0914”(association)	0.640
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
TSPAN2	TSPAN3	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
ATP5PF	SLC19A2	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
	ESYT2	psi-mi:“MI:0914”(association)	0.350
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
TACR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC5A8	GPR89A	psi-mi:“MI:0914”(association)	0.350
OPRM1	EXOC5	psi-mi:“MI:0914”(association)	0.350
CHRM4	GEMIN2	psi-mi:“MI:0914”(association)	0.350
VTN	HAT1	psi-mi:“MI:0914”(association)	0.350
SLC22A16	AGPAT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (118): LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Proximity Label-MS), LPCAT3 (Proximity Label-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3STV6, A0A0P0WY03, A0A161IUT7, A0A1L7VI12, A8WXS4, A8WZ09, B1Q006, I1MSF2, K7LC65, O01925, O42916, O74380, P0DO28, P25628, P52887, P53154, P53730, P53868, P86935, Q08548, Q08929, Q09758, Q0WW17, Q10269, Q19468, Q22329, Q3SZL3, Q3T1J2, Q5FVN0, Q5GKZ7, Q5I396, Q5ZKL6, Q6CK18, Q6NN55, Q6P1A2, Q6Q889, Q6ZNC8, Q6ZWT7, Q7Q3N5, Q7Z7B1

Diamond homologs: O01925, Q3SZL3, Q5FVN0, Q6P1A2, Q91V01, Q9VVX5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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
R-HSA-425366	6	13.4×	4e-04
SLC-mediated transmembrane transport	13	9.5×	2e-07
Class A/1 (Rhodopsin-like receptors)	7	6.4×	5e-03
G alpha (q) signalling events	9	6.4×	6e-04
GPCR ligand binding	7	5.5×	9e-03
Transport of small molecules	15	4.7×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	5	15.6×	4e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	9	11.8×	4e-05
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	5	10.9×	1e-02
positive regulation of cytosolic calcium ion concentration	7	8.2×	4e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	7	7.9×	4e-03
G protein-coupled receptor signaling pathway	12	4.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2585 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6976889:CAC:C	acceptor_gain	1.0000
12:6976892:C:CA	acceptor_loss	1.0000
12:6976892:C:CC	acceptor_gain	1.0000
12:6977128:ACTT:A	donor_loss	1.0000
12:6977129:CTTA:C	donor_loss	1.0000
12:6977130:TTACC:T	donor_loss	1.0000
12:6977131:TAC:T	donor_loss	1.0000
12:6977132:A:AC	donor_gain	1.0000
12:6977132:A:C	donor_loss	1.0000
12:6977133:C:CC	donor_gain	1.0000
12:6977258:TACAC:T	acceptor_gain	1.0000
12:6977259:ACACC:A	acceptor_loss	1.0000
12:6977260:CAC:C	acceptor_gain	1.0000
12:6977263:CT:C	acceptor_loss	1.0000
12:6977264:T:C	acceptor_loss	1.0000
12:6977365:GCC:G	donor_loss	1.0000
12:6977366:C:CT	donor_loss	1.0000
12:6977370:AAG:A	donor_gain	1.0000
12:6977521:GCAGC:G	acceptor_gain	1.0000
12:6977522:CAGC:C	acceptor_gain	1.0000
12:6977522:CAGCC:C	acceptor_gain	1.0000
12:6977523:AGC:A	acceptor_gain	1.0000
12:6977524:GC:G	acceptor_gain	1.0000
12:6977525:CC:C	acceptor_gain	1.0000
12:6977526:C:CC	acceptor_gain	1.0000
12:6977526:C:T	acceptor_gain	1.0000
12:6978504:CTTC:C	acceptor_gain	1.0000
12:6978508:C:CC	acceptor_gain	1.0000
12:6978595:CTACT:C	donor_loss	1.0000
12:6978596:TACTT:T	donor_loss	1.0000

AlphaMissense

3180 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6978370:G:C	F337L	1.000
12:6978370:G:T	F337L	1.000
12:6978372:A:G	F337L	1.000
12:6981833:A:C	C146W	1.000
12:6981850:A:G	W141R	1.000
12:6981850:A:T	W141R	1.000
12:6977397:G:C	F439L	0.999
12:6977397:G:T	F439L	0.999
12:6977399:A:G	F439L	0.999
12:6977634:G:C	F384L	0.999
12:6977634:G:T	F384L	0.999
12:6977636:A:G	F384L	0.999
12:6977666:G:C	H374D	0.999
12:6977669:A:G	W373R	0.999
12:6977669:A:T	W373R	0.999
12:6978367:G:C	N338K	0.999
12:6978367:G:T	N338K	0.999
12:6978371:A:G	F337S	0.999
12:6978504:C:G	G293R	0.999
12:6978504:C:T	G293R	0.999
12:6978612:C:A	W288C	0.999
12:6978612:C:G	W288C	0.999
12:6978614:A:G	W288R	0.999
12:6978614:A:T	W288R	0.999
12:6981834:C:T	C146Y	0.999
12:6981848:C:A	W141C	0.999
12:6981848:C:G	W141C	0.999
12:6977635:A:G	F384S	0.998
12:6977650:C:T	G379E	0.998
12:6977662:C:A	G375V	0.998

dbSNP variants (sampled 300 via entrez): RS1000224637 (12:6982231 G>A,C,T), RS1000241626 (12:6989889 T>A), RS1000343388 (12:7015093 G>C,T), RS1000388112 (12:6996876 G>A), RS1000501528 (12:6988333 A>C,G), RS1000694222 (12:6994609 G>A), RS1000930753 (12:7001789 T>C), RS1000979477 (12:6988605 C>T), RS1001104905 (12:7007930 A>T), RS1001256393 (12:7001506 C>G,T), RS1001476495 (12:7016026 G>T), RS1001654525 (12:7008073 T>C), RS1001911356 (12:6982936 T>A,C), RS1002005198 (12:6988742 A>G), RS1002413230 (12:7002383 C>A,T)

Disease associations

OMIM: gene MIM:611950 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002712_10	Red blood cell fatty acid levels	3.000000e-30
GCST002712_13	Red blood cell fatty acid levels	3.000000e-49
GCST004338_3	Oleic acid (18:1n-9) levels	2.000000e-08
GCST004621_29	Red cell distribution width	2.000000e-17
GCST004747_3	Lung cancer in never smokers	9.000000e-06
GCST006018_3	Activated partial thromboplastin time	1.000000e-09
GCST90002381_536	Eosinophil count	9.000000e-10
GCST90002382_305	Eosinophil percentage of white cells	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006807	linoleic acid measurement
EFO:0006810	oleic acid measurement
EFO:0009188	Red cell distribution width
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066416 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.11	Kd	7683	nM	CHEMBL5653589
5.11	ED50	7683	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2148662: Binding affinity to human LPCAT3 incubated for 45 mins by Kinobead based pull down assay	kd	7.6834	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Acetaminophen	increases expression, decreases expression	2
Benzo(a)pyrene	decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
methyleugenol	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
ciglitazone	affects binding, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Microplastics	affects expression, increases abundance	1
Air Pollutants	increases abundance, decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Isoniazid	increases expression	1
Ivermectin	increases expression	1
Polyethylene Terephthalates	affects expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651704	Binding	Binding affinity to human LPCAT3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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