LPCAT1

Summary

LPCAT1 (lysophosphatidylcholine acyltransferase 1, HGNC:25718) is a protein-coding gene on chromosome 5p15.33, encoding Lysophosphatidylcholine acyltransferase 1 (Q8NF37). Exhibits acyltransferase activity.

This gene encodes a member of the 1-acyl-sn-glycerol-3-phosphate acyltransferase family of proteins. The encoded enzyme plays a role in phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine to phosphatidylcholine in the presence of acyl-CoA. This process is important in the synthesis of lung surfactant and platelet-activating factor (PAF). Elevated expression of this gene may contribute to the progression of oral squamous cell, prostate, breast, and other human cancers.

Source: NCBI Gene 79888 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 85 total
• Druggable target: yes
• MANE Select transcript: NM_024830

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25718
Approved symbol	LPCAT1
Name	lysophosphatidylcholine acyltransferase 1
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12443, AGPAT9, AGPAT10, LPLAT8
Ensembl gene	ENSG00000153395
Ensembl biotype	protein_coding
OMIM	610472
Entrez	79888

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000283415, ENST00000475622, ENST00000503252, ENST00000507282, ENST00000513757, ENST00000514484, ENST00000879554, ENST00000934189, ENST00000934190, ENST00000934191, ENST00000968003, ENST00000968004

RefSeq mRNA: 1 — MANE Select: NM_024830 NM_024830

CCDS: CCDS3864

Canonical transcript exons

ENST00000283415 — 14 exons

Exon	Start	End
ENSE00001010521	1470826	1470924
ENSE00001010524	1473957	1474110
ENSE00001010525	1479621	1479675
ENSE00001010529	1477404	1477486
ENSE00001010530	1474560	1474685
ENSE00003512062	1494700	1494914
ENSE00003565978	1489746	1489858
ENSE00003580873	1501461	1501603
ENSE00003634671	1480942	1480976
ENSE00003662573	1488391	1488451
ENSE00003686989	1466749	1466890
ENSE00003694187	1483428	1483486
ENSE00004030969	1461427	1463835
ENSE00004030976	1523710	1523960

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.6000 / max 910.9452, expressed in 1802 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60810	32.5069	1797
60798	1.2067	172
60812	1.0967	605
60811	0.5582	214
60782	0.4756	250
60784	0.2930	39
60785	0.2074	35
60799	0.1492	53
60800	0.1063	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	98.05	gold quality
spleen	UBERON:0002106	97.76	gold quality
ventricular zone	UBERON:0003053	97.70	gold quality
granulocyte	CL:0000094	97.19	gold quality
right lung	UBERON:0002167	97.06	gold quality
lung	UBERON:0002048	96.95	gold quality
embryo	UBERON:0000922	96.74	gold quality
ganglionic eminence	UBERON:0004023	96.74	gold quality
blood	UBERON:0000178	96.17	gold quality
cortical plate	UBERON:0005343	93.58	gold quality
lymph node	UBERON:0000029	93.49	gold quality
leukocyte	CL:0000738	93.45	gold quality
monocyte	CL:0000576	93.11	gold quality
vermiform appendix	UBERON:0001154	92.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.88	gold quality
bone marrow cell	CL:0002092	91.62	gold quality
placenta	UBERON:0001987	91.55	gold quality
cerebellar hemisphere	UBERON:0002245	91.51	gold quality
cerebellar cortex	UBERON:0002129	91.45	gold quality
cerebellum	UBERON:0002037	91.42	gold quality
bone marrow	UBERON:0002371	91.25	gold quality
bone element	UBERON:0001474	91.24	gold quality
ascending aorta	UBERON:0001496	91.14	gold quality
thoracic aorta	UBERON:0001515	91.04	gold quality
descending thoracic aorta	UBERON:0002345	90.84	gold quality
adenohypophysis	UBERON:0002196	90.77	gold quality
stromal cell of endometrium	CL:0002255	90.74	gold quality
pituitary gland	UBERON:0000007	90.69	gold quality
gall bladder	UBERON:0002110	90.59	gold quality
left uterine tube	UBERON:0001303	90.52	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	94.09
E-ANND-3	yes	22.80
E-GEOD-130148	yes	12.96
E-GEOD-75367	no	201.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting LPCAT1, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809

Literature-anchored findings (GeneRIF, showing 40)

• Aytl2 gene is the phosphatidylcholine reacylating enzyme in RBCs; this represents the identification of a plasma membrane lysophospholipid acyltransferase and establishes the function of a LPCAT protein (PMID:18156367)
• LPCAT1 may contribute to total choline metabolite accumulation via phosphatidylcholine remodeling, thereby altering the CRC lipid profile, a characteristic of malignancy. (PMID:18974965)
• hLPCAT1 is the biosynthetic enzyme of pulmonary surfactant phospholipids. (PMID:19383981)
• full LPCAT1 activity is required to achieve the levels of SatPC essential for the transition to air breathing (PMID:20407208)
• LPCAT1 and -2 have, in addition to their known function in specialized cells, a ubiquitous role in LD-associated lipid metabolism (PMID:21498505)
• LPCAT1 correlates with the progression of prostate cancer. (PMID:22101258)
• effect of LPCAT1 overexpression or knockdown on cell proliferation, migration, and invasion in hepatocellular carcinoma cell lines (PMID:23567080)
• The prognostic impact of LPCAT1 expression was independent of histological and clinical parameters. It is concluded, that LPCAT1 measurement, either alone or in combination, may be utilized for better clinical decision-making. (PMID:23941784)
• LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. (PMID:24418166)
• LPCAT1 is an independent predictor of early tumor recurrence of breast carcinoma and represents a novel prognostic biomarker that reflects underlying biological alterations (PMID:25683484)
• Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations are associated with Gastric Cancer (PMID:25752890)
• Down-regulation of LPCAT1 resulted in a decreased intercellular platelet-activating factor concentration and PAFR expression. (PMID:25803864)
• We found a direct correlation between LPCAT1 mRNA copies and the amniotic fluid lamellar body count. This finding corroborates an association between LPCAT1 and surfactant phospholipid biosynthesis. (PMID:25968427)
• No disease causing mutations in the LPCAT1 gene were identified, indicating that LPCAT1 either does not confer a genetic predisposition to retinitis pigmentosa, or incidence of mutations in LPCAT1 is particularly rare in patients with retinitis pigmentosa. (PMID:26260533)
• The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC. (PMID:28494778)
• fetal LPCAT1 mRNA present in maternal blood in quantity that correlates with lamellar body count (PMID:28926341)
• LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma. (PMID:30791942)
• Up-regulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) is linked to poor prognosis in breast cancer. (PMID:31533087)
• Genetic Polymorphisms of LPCAT1, CHPT1 and PCYT1B and Risk of Neonatal Respiratory Distress Syndrome among a Chinese Han Population. (PMID:31964590)
• A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers. (PMID:32334831)
• LPCAT1 enhances castration resistant prostate cancer progression via increased mRNA synthesis and PAF production. (PMID:33137125)
• Methylome and transcriptome profiling revealed epigenetic silencing of LPCAT1 and PCYT1A associated with lipidome alterations in polycystic ovary syndrome. (PMID:33521992)
• Molecular mechanisms regulating lysophosphatidylcholine acyltransferase 1 (LPCAT1) in human pregnancy. (PMID:33618181)
• Polypeptide N-acetylgalactosaminyltransferase 18 retains in endoplasmic reticulum depending on its luminal regions interacting with ER resident UGGT1, PLOD3 and LPCAT1. (PMID:33909026)
• LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. (PMID:34033669)
• Increased lysophosphatidylcholine acyltransferase 1 expression is unrelated to prognosis of esophageal cancer patients. (PMID:34148155)
• LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways. (PMID:34358528)
• Differential lysophosphatidylcholine acyltransferase 1 (LPCAT1) expression confers aggressiveness and independently predicts recurrence in bladder urothelial carcinomas. (PMID:34378492)
• LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma. (PMID:34518524)
• Circular RNA circZCCHC6 contributes to tumorigenesis by regulating LPCAT1 via miR-433-3p in non-small cell lung cancer. (PMID:35089454)
• Lysophosphatidylcholine acyltransferase 1 promotes pathology and toxicity in two distinct cell-based alpha-synuclein models. (PMID:35108590)
• Lysophosphatidylcholine Acyltransferase 1 Deficiency Promotes Pulmonary Emphysema via Apoptosis of Alveolar Epithelial Cells. (PMID:35338433)
• ncRNA-Mediated High Expression of LPCAT1 Correlates with Poor Prognosis and Tumor Immune Infiltration of Liver Hepatocellular Carcinoma. (PMID:35615532)
• Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/beta-Smad2/3 signaling pathway. (PMID:35880567)
• Lysophosphatidylcholine acyltransferase 1 protein is present in maternal blood in the third trimester and is upregulated by antenatal corticosteroids. (PMID:36084307)
• LPCAT1 functions as an oncogene in cervical cancer through mediating JAK2/STAT3 signaling. (PMID:36122769)
• LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma. (PMID:36307879)
• sn-1 Specificity of Lysophosphatidylcholine Acyltransferase-1 Revealed by a Mass Spectrometry-Based Assay. (PMID:36478519)
• [Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2]. (PMID:36765478)
• The validation and clinical significance of LPCAT1 down-regulation in acute myeloid leukemia. (PMID:37079124)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpcat1	ENSDARG00000011506
danio_rerio		ENSDARG00000115651
mus_musculus	Lpcat1	ENSMUSG00000021608
rattus_norvegicus	Lpcat1	ENSRNOG00000017930
drosophila_melanogaster	LPCAT	FBGN0052699

Paralogs (4): LPCAT2 (ENSG00000087253), GPAT3 (ENSG00000138678), GPAT4 (ENSG00000158669), LPCAT4 (ENSG00000176454)

Protein

Protein identifiers

Lysophosphatidylcholine acyltransferase 1 — Q8NF37 (reviewed: Q8NF37)

Alternative names: 1-acylglycerol-3-phosphate O-acyltransferase, 1-acylglycerophosphocholine O-acyltransferase, 1-alkenylglycerophosphocholine O-acyltransferase, 1-alkylglycerophosphocholine O-acetyltransferase, Acetyl-CoA:lyso-platelet-activating factor acetyltransferase, Acyltransferase-like 2, Phosphonoformate immuno-associated protein 3

All UniProt accessions (1): Q8NF37

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits acyltransferase activity. Exhibits acetyltransferase activity. Activity is calcium-independent. Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. Displays a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively. Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF). May synthesize phosphatidylcholine in pulmonary surfactant, thereby playing a pivotal role in respiratory physiology. Involved in the regulation of lipid droplet number and size.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell membrane. Lipid droplet.

Tissue specificity. Erythrocytes.

Domain organisation. The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphocholine. The di-lysine motif may confer endoplasmic reticulum localization.

Pathway. Lipid metabolism; phospholipid metabolism.

Similarity. Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.

RefSeq proteins (1): NP_079106* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR002123	Plipid/glycerol_acylTrfase	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR045252	LPCAT1-like	Domain

Pfam: PF01553, PF13833

Enzyme classification (BRENDA):

• EC 2.3.1.23 — 1-acylglycerophosphocholine O-acyltransferase (BRENDA: 25 organisms, 283 substrates, 101 inhibitors, 64 Km, 2 kcat entries)
• EC 2.3.1.51 — 1-acylglycerol-3-phosphate O-acyltransferase (BRENDA: 39 organisms, 381 substrates, 31 inhibitors, 32 Km, 4 kcat entries)
• EC 2.3.1.62 — 2-acylglycerophosphocholine O-acyltransferase (BRENDA: 9 organisms, 37 substrates, 10 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

25 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
1-ACYL-SN-GLYCEROL 3-PHOSPHATE	0.0053–0.125	8
OLEOYL-COA	0.0027–0.0215	8
PALMITOYL-COA	0.0014–0.012	8
ARACHIDONOYL-COA	0.0032–0.7156	6
1-OLEOYL-SN-GLYCEROL 3-PHOSPHATE	0.0048–0.018	5
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

Catalyzed reactions (Rhea), 12 shown:

• a 1-O-(1Z-alkenyl)-sn-glycero-3-phosphocholine + an acyl-CoA = a 1-O-(1Z-alkenyl)-2-acyl-sn-glycero-3-phosphocholine + CoA (RHEA:10344)
• a 1-acyl-sn-glycero-3-phosphocholine + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphocholine + CoA (RHEA:12937)
• a 1-O-alkyl-sn-glycero-3-phosphocholine + acetyl-CoA = a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + CoA (RHEA:18461)
• a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA (RHEA:19709)
• 1-acyl-sn-glycero-3-phospho-(1’-sn-glycerol) + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol) + CoA (RHEA:33203)
• a 1-acyl-sn-glycero-3-phosphate + hexadecanoyl-CoA = 1-acyl-2-hexadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:33315)
• 1-hexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + hexadecanoyl-CoA = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + CoA (RHEA:35851)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoyl-CoA = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + CoA (RHEA:35983)
• 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)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + hexadecanoyl-CoA = 1-(9Z-octadecenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine + CoA (RHEA:37383)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine + CoA (RHEA:37475)

UniProt features (17 total): binding site 5, topological domain 2, compositionally biased region 2, domain 2, region of interest 2, short sequence motif 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NF37-F1	82.85	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 392; 394; 396; 398; 403

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482925	Acyl chain remodelling of PG
R-HSA-1483166	Synthesis of PA
R-HSA-1483191	Synthesis of PC
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 316 (showing top): GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GOCC_VACUOLAR_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOCC_SECRETORY_GRANULE, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HASLINGER_B_CLL_WITH_MUTATED_VH_GENES, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (12): phosphatidic acid biosynthetic process (GO:0006654), phosphatidylcholine biosynthetic process (GO:0006656), phospholipid biosynthetic process (GO:0008654), protein catabolic process (GO:0030163), phosphatidylglycerol acyl-chain remodeling (GO:0036148), phosphatidylcholine acyl-chain remodeling (GO:0036151), surfactant homeostasis (GO:0043129), positive regulation of protein catabolic process (GO:0045732), retina development in camera-type eye (GO:0060041), negative regulation of phosphatidylcholine biosynthetic process (GO:2001246), lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644)

GO Molecular Function (12): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), calcium ion binding (GO:0005509), lysophosphatidic acid acyltransferase activity (GO:0042171), 2-acylglycerol-3-phosphate O-acyltransferase activity (GO:0047144), plasmalogen synthase activity (GO:0047159), 1-acylglycerophosphocholine O-acyltransferase activity (GO:0047184), 1-alkylglycerophosphocholine O-acyltransferase activity (GO:0047191), 1-alkylglycerophosphocholine O-acetyltransferase activity (GO:0047192), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872)

GO Cellular Component (8): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), lipid droplet (GO:0005811), plasma membrane (GO:0005886), membrane (GO:0016020), azurophil granule membrane (GO:0035577)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	4
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acyltransferase activity, transferring groups other than amino-acyl groups	3
glycerophospholipid biosynthetic process	2
phosphatidylcholine metabolic process	2
lysophosphatidic acid acyltransferase activity	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
phosphatidic acid metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
macromolecule catabolic process	1
protein metabolic process	1
phosphatidylglycerol metabolic process	1
multicellular organismal-level chemical homeostasis	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
camera-type eye development	1
anatomical structure development	1
phosphatidylcholine biosynthetic process	1
negative regulation of phospholipid biosynthetic process	1
regulation of phosphatidylcholine biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
organophosphate metabolic process	1
acylglycerol O-acyltransferase activity	1
metal ion binding	1
lysophospholipid acyltransferase activity	1
O-acetyltransferase activity	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1792 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPCAT1	LPCAT3	Q6P1A2	741
LPCAT1	FGF7	P21781	739
LPCAT1	SFTPB	P07988	615
LPCAT1	CHPT1	Q8WUD6	605
LPCAT1	DGAT2	Q96PD7	587
LPCAT1	CLPTM1L	Q96KA5	577
LPCAT1	ABCA3	Q99758	570
LPCAT1	MBOAT2	Q6ZWT7	556
LPCAT1	AGPAT3	Q9NRZ7	555
LPCAT1	PLA2G7	Q13093	545
LPCAT1	AGPAT1	Q99943	529
LPCAT1	SMPD4	Q9NXE4	516
LPCAT1	SFTPC	P11686	494
LPCAT1	DGAT1	O75907	488
LPCAT1	PCYT1B	Q9Y5K3	469

IntAct

69 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
LPCAT1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	ZW10	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
TPTE	ILVBL	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAP2K7	ILVBL	psi-mi:“MI:0914”(association)	0.350
MAPK4	ILVBL	psi-mi:“MI:0914”(association)	0.350
GRK6	ILVBL	psi-mi:“MI:0914”(association)	0.350
STYK1	XPO1	psi-mi:“MI:0914”(association)	0.350
ADCK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
CDK20	APOD	psi-mi:“MI:0914”(association)	0.350
COQ8A	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (174): BBS2 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), SLC27A2 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DIP2A (Affinity Capture-MS), LPCAT1 (Affinity Capture-MS), LPCAT1 (Proximity Label-MS), LPCAT1 (Affinity Capture-MS), BTRC (Affinity Capture-Western), LPCAT1 (Biochemical Activity), LPCAT1 (Biochemical Activity), SLC27A2 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MTR (Affinity Capture-MS), DIP2A (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

Diamond homologs: P0C1Q3, Q0KHU5, Q1HAQ0, Q1LWG4, Q28C60, Q3TFD2, Q4V8A1, Q502J0, Q643R3, Q6DCK1, Q6NVG1, Q7L5N7, Q8BYI6, Q8L7R3, Q8NF37, Q9D5U0, Q9HW50, Q8S8S2, O73761, P43080, P46065, Q16982, Q8VBV8, G5EDN6, P48451, Q24214, Q3HRN9, P0A257, P0A258, P26647, A0AAR7, B3DLU1, B3VSB7, F8VPZ3, M9PD06, O73763, O81445, P05933, P21457, P22728

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
LPCAT1	“up-regulates quantity”	1,2-diacyl-sn-glycero-3-phosphocholine	“chemical modification”
LPCAT1	“up-regulates quantity”	“coenzyme A(4-)”	“chemical modification”
LPCAT1	“down-regulates quantity”	1-O-acyl-sn-glycero-3-phosphocholine	“chemical modification”
LPCAT1	“down-regulates quantity”	acyl-CoA(4-)	“chemical modification”
SCF-betaTRCP	“down-regulates quantity by destabilization”	LPCAT1	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3330 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1466888:CAT:C	acceptor_gain	1.0000
5:1466889:ATCT:A	acceptor_loss	1.0000
5:1466890:TCTGC:T	acceptor_loss	1.0000
5:1466891:CTG:C	acceptor_loss	1.0000
5:1466892:T:A	acceptor_loss	1.0000
5:1470821:CTCA:C	donor_loss	1.0000
5:1470822:TCAC:T	donor_loss	1.0000
5:1470823:CACC:C	donor_loss	1.0000
5:1470824:A:AC	donor_gain	1.0000
5:1470824:A:AG	donor_loss	1.0000
5:1470824:AC:A	donor_gain	1.0000
5:1470825:C:CC	donor_gain	1.0000
5:1470825:CC:C	donor_gain	1.0000
5:1474556:TCAC:T	donor_loss	1.0000
5:1474558:A:AC	donor_gain	1.0000
5:1474558:A:C	donor_loss	1.0000
5:1474558:AC:A	donor_gain	1.0000
5:1474559:C:CA	donor_loss	1.0000
5:1474559:C:CC	donor_gain	1.0000
5:1474559:CC:C	donor_gain	1.0000
5:1477398:A:AC	donor_gain	1.0000
5:1477399:C:CC	donor_gain	1.0000
5:1477399:CTTA:C	donor_gain	1.0000
5:1477400:TTA:T	donor_loss	1.0000
5:1477401:TA:T	donor_loss	1.0000
5:1477402:A:AC	donor_gain	1.0000
5:1477402:A:C	donor_loss	1.0000
5:1477403:C:CC	donor_gain	1.0000
5:1477403:CT:C	donor_gain	1.0000
5:1477403:CTCG:C	donor_gain	1.0000

AlphaMissense

3443 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:1483479:G:C	F225L	0.999
5:1483479:G:T	F225L	0.999
5:1483481:A:G	F225L	0.999
5:1483462:A:T	V231D	0.998
5:1488398:G:C	F220L	0.998
5:1488398:G:T	F220L	0.998
5:1488400:A:G	F220L	0.998
5:1477431:G:T	A291D	0.997
5:1483480:A:G	F225S	0.997
5:1488395:T:A	K221N	0.997
5:1488395:T:G	K221N	0.997
5:1488440:A:C	F206L	0.997
5:1488440:A:T	F206L	0.997
5:1488442:A:G	F206L	0.997
5:1489828:A:T	V175E	0.997
5:1494790:G:C	H135D	0.997
5:1477408:C:G	A299P	0.996
5:1477419:C:G	R295P	0.996
5:1480964:A:G	W247R	0.996
5:1480964:A:T	W247R	0.996
5:1488399:A:G	F220S	0.996
5:1488400:A:T	F220I	0.996
5:1494783:G:A	S137F	0.996
5:1523749:G:C	F32L	0.996
5:1523749:G:T	F32L	0.996
5:1523751:A:G	F32L	0.996
5:1483481:A:T	F225I	0.995
5:1483486:C:T	G223D	0.995
5:1488419:G:C	N213K	0.995
5:1488419:G:T	N213K	0.995

dbSNP variants (sampled 300 via entrez): RS1000035393 (5:1471631 C>A), RS1000075010 (5:1493038 A>G), RS1000090341 (5:1471854 C>T), RS1000109327 (5:1501946 A>C), RS1000125181 (5:1502475 G>A), RS1000180865 (5:1518626 C>A,T), RS1000264878 (5:1466978 G>A,T), RS1000291346 (5:1523289 C>T), RS1000298881 (5:1475268 T>C,G), RS1000311462 (5:1514412 C>T), RS1000314094 (5:1462906 T>C), RS1000367202 (5:1515315 C>T), RS1000395971 (5:1474702 A>C), RS1000414686 (5:1494166 C>T), RS1000431062 (5:1510802 G>A)

Disease associations

OMIM: gene MIM:610472 | 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
GCST001762_177	Obesity-related traits	9.000000e-06
GCST002553_8	Pancreatic cancer	1.000000e-13
GCST004744_48	Lung adenocarcinoma	6.000000e-06
GCST004749_104	Lung cancer in ever smokers	9.000000e-06
GCST007847_43	Type 2 diabetes	2.000000e-12
GCST009391_1007	Metabolite levels	5.000000e-06
GCST009597_309	Multiple sclerosis	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004627	IGF-1 measurement
EFO:0010359	lysophosphatidylcholine 18:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295903 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2292023	LPCAT1, SLC6A3		0.00	0

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
6.05	Kd	896	nM	CHEMBL3752910
6.05	ED50	896	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 3 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148661: Binding affinity to human LPCAT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8960	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases stability, affects cotreatment, increases abundance, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
bisphenol A	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Dexamethasone	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, affects expression	2
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pirinixic acid	increases activity, increases expression, affects binding	1
sodium arsenate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
ciglitazone	affects binding, increases 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
CHEMBL4119000	Binding	Binding affinity to LPCAT1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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