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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 10 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈8% of expected missense variation)
• GTEx eGene: eQTL in 10 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.48 (moderately constrained)
• 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: 37 — 16 protein_coding, 14 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000261407

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2, TSL 3: 1, TSL 4: 4, TSL 5: 2

ENST00000261407, ENST00000535021, ENST00000535479, ENST00000536797, ENST00000536971, ENST00000537179, ENST00000538910, ENST00000538987, ENST00000540060, ENST00000540090, ENST00000543794, ENST00000545459, ENST00000620843, ENST00000907763, ENST00000907764, ENST00000907765, ENST00000907766, ENST00000907767, ENST00000907768, ENST00000925113, ENST00000925114, ENST00000954703, ENST00000954704, ENST00000954705, ENST00001002188, ENST00001002189, ENST00001002190, ENST00001002197, ENST00001018225, ENST00001018226, ENST00001018227, ENST00001072339, ENST00001072341, ENST00001072342, ENST00001072343, ENST00001105912, ENST00001142369

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.

Highest expression (Bgee): lobe of liver, adrenal gland, mucosa of transverse colon, body of stomach, rectum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPCAT3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.7e-54	+0.48	12:7003757:T:C
Brain Cerebellar Hemisphere	eqtl	3.1e-11	-0.72	12:6966050:G:T
Brain Cerebellum	eqtl	2.2e-08	-0.76	12:6966050:G:T
Stomach	eqtl	2.6e-05	-0.22	12:7022815:C:T
Artery Aorta	eqtl	9.6e-03	-0.52	12:7506391:G:T
Brain Substantia nigra	eqtl	2.1e-02	-0.27	12:7715864:C:T
Artery Coronary	eqtl	2.3e-02	-0.19	12:6129313:C:T
Adipose Subcutaneous	sqtl	2.7e-02	-0.30	12:7006671:C:T
Brain Cortex	eqtl	3.2e-02	-0.40	12:6976009:G:A
Artery Tibial	eqtl	3.9e-02	-0.38	12:7893084:G:A
Esophagus Muscularis	eqtl	4.2e-02	-0.07	12:7839844:C:T

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 287 tissues 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
peritoneum	UBERON:0002358	92.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.11	gold quality
saliva-secreting gland	UBERON:0001044	92.06	gold quality
heart left ventricle	UBERON:0002084	91.97	gold quality
muscle of leg	UBERON:0001383	91.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.92	gold quality
thyroid gland	UBERON:0002046	91.82	gold quality
cardiac ventricle	UBERON:0002082	91.79	gold quality
cerebellar hemisphere	UBERON:0002245	91.70	gold quality
type B pancreatic cell	CL:0000169	91.68	gold quality
cerebellar cortex	UBERON:0002129	91.63	gold quality
monocyte	CL:0000576	91.59	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.37	gold quality
intestine	UBERON:0000160	91.36	gold quality
skin of leg	UBERON:0001511	91.21	gold quality
left uterine tube	UBERON:0001303	91.19	gold quality
esophagus mucosa	UBERON:0002469	91.13	gold quality
colon	UBERON:0001155	91.02	gold quality
mononuclear cell	CL:0000842	90.96	gold quality
leukocyte	CL:0000738	90.93	gold quality
esophagus	UBERON:0001043	90.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.87	gold quality
fundus of stomach	UBERON:0001160	90.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.71	gold quality
large intestine	UBERON:0000059	90.69	gold quality
lower esophagus	UBERON:0013473	90.69	gold quality
right coronary artery	UBERON:0001625	90.55	gold quality
ectocervix	UBERON:0012249	90.40	gold quality
colonic epithelium	UBERON:0000397	90.34	gold quality
muscle organ	UBERON:0001630	90.28	gold quality
skeletal muscle organ	UBERON:0014892	90.28	gold quality
apex of heart	UBERON:0002098	90.27	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.25	gold quality
cerebellum	UBERON:0002037	90.15	gold quality
adult mammalian kidney	UBERON:0000082	90.12	gold quality
prostate gland	UBERON:0002367	90.07	gold quality
granulocyte	CL:0000094	89.99	gold quality
smooth muscle tissue	UBERON:0001135	89.74	gold quality
mucosa of stomach	UBERON:0001199	89.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.62	gold quality
heart	UBERON:0000948	89.61	gold quality
gall bladder	UBERON:0002110	89.59	gold quality
right uterine tube	UBERON:0001302	89.48	gold quality
left coronary artery	UBERON:0001626	89.48	gold quality
triceps brachii	UBERON:0001509	89.47	silver quality
diaphragm	UBERON:0001103	89.43	gold quality
nipple	UBERON:0002030	89.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.32	silver quality
bone marrow cell	CL:0002092	89.28	gold quality
tonsil	UBERON:0002372	89.25	gold quality
coronary artery	UBERON:0001621	89.18	gold quality
zone of skin	UBERON:0000014	89.12	gold quality
right ovary	UBERON:0002118	89.12	gold quality
endocervix	UBERON:0000458	89.11	gold quality
blood	UBERON:0000178	89.03	gold quality
sigmoid colon	UBERON:0001159	88.81	gold quality
lower esophagus mucosa	UBERON:0035834	88.76	gold quality
stromal cell of endometrium	CL:0002255	88.62	gold quality
lymph node	UBERON:0000029	88.41	gold quality
descending thoracic aorta	UBERON:0002345	88.40	gold quality
vagina	UBERON:0000996	88.35	gold quality
right atrium auricular region	UBERON:0006631	88.32	gold quality
caecum	UBERON:0001153	88.20	gold quality
popliteal artery	UBERON:0002250	88.15	gold quality
tibial artery	UBERON:0007610	88.14	gold quality
vermiform appendix	UBERON:0001154	88.13	gold quality
adipose tissue	UBERON:0001013	88.08	gold quality
tibial nerve	UBERON:0001323	88.05	gold quality
nerve	UBERON:0001021	88.04	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Duodenum	tissue	115.6
Small intestine	tissue	93.8
Liver	tissue	80.9
Stomach 1	tissue	54.9
Tongue	tissue	53.7
Colon	tissue	48.1
Rectum	tissue	45.0
Lung	tissue	43.3
Kidney	tissue	41.4
Placenta	tissue	35.6
Pancreas	tissue	34.3
Prostate	tissue	33.7
Salivary gland	tissue	32.9
Urinary bladder	tissue	32.9
Breast	tissue	29.3
Skin 1	tissue	26.8
Bone marrow	tissue	26.6
Adipose tissue	tissue	24.2
Thyroid gland	tissue	22.9
Adrenal gland	tissue	21.7
Vagina	tissue	20.9
Epididymis	tissue	20.3
Appendix	tissue	20.3
Smooth muscle	tissue	20.2
Thymus	tissue	20.0
Esophagus	tissue	19.8
Tonsil	tissue	19.8
Cervix	tissue	19.0
Parathyroid gland	tissue	18.4
Cerebellum	tissue	17.8
Skeletal muscle	tissue	17.6
Gallbladder	tissue	17.4
Periaqueductal gray	tissue	16.1
Lymph node	tissue	15.9
Seminal vesicle	tissue	15.4
Hypothalamus	tissue	15.2
Spinal cord	tissue	15.2
Caudate putamen	tissue	15.2
Fallopian tube	tissue	15.0
Substantia nigra	tissue	14.9
Pituitary gland	tissue	14.7
Corpus callosum	tissue	14.4
Hippocampal formation	tissue	14.4
Medulla oblongata	tissue	13.9
Septum	tissue	13.9
Amygdala	tissue	13.1
Superior colliculi	tissue	12.6
Pons	tissue	12.5
Heart muscle	tissue	12.4
Frontal cortex	tissue	12.4
Midbrain	tissue	12.3
Olfactory bulb	tissue	12.3
Cerebral cortex	tissue	11.5
Thalamus	tissue	11.5
Temporal cortex	tissue	11.5
Prefrontal cortex	tissue	11.4
Endometrium 1	tissue	11.3
Choroid plexus	tissue	11.3
Entorhinal cortex	tissue	11.3
Motor cortex	tissue	11.0

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (21.8), Dorsal spinal cord (15.2), Ventral spinal cord (15.0), Ventral hippocampus (14.4), White matter (14.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H3

miRNA regulators (miRDB)

Targeting LPCAT3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 87 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.991, LOEUF 0.485, missense Z 2.11 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000261407 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈8% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:6,977,149–6,981,601	304 / 390.8	0.78	no
12:6,981,602–6,981,897	14 / 47.8	0.29	yes (p 1.0e-06)
12:6,981,898–7,018,424	133 / 152.1	0.87	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1315211) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal enterocyte morphology	1
abnormal liver physiology	1
decreased body weight	1
abnormal lipid level	1
postnatal growth retardation	1
abnormal lipid homeostasis	1
hepatic steatosis	1
decreased circulating triglyceride level	1
decreased circulating insulin level	1
decreased circulating VLDL triglyceride level	1
abnormal phospholipid level	1
decreased circulating glucose level	1
increased liver triglyceride level	1
increased liver cholesterol level	1
abnormal circulating apolipoprotein level	1
postnatal lethality, complete penetrance	1
abnormal lipid metabolism	1
decreased circulating VLDL phospholipid level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3SZL3	87.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
EMG1	protein-coding	10436
PHB2	protein-coding	11331
SCARNA12	ncRNA	677777
C1S	protein-coding	716
C1R	protein-coding	715
MIR200CHG	ncRNA	105369635
MIR141	ncRNA	406933
MIR200C	ncRNA	406985
PTPN6	protein-coding	5777

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): B7Z3N5, F5GYT3, F5H0M4, F5H680, F5H7K7, Q6P1A2

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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted membrane proteins

Protein evidence: Evidence at protein level

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)

Position	Role
338
374

Post-translational modifications (1)

Type	Positions
N-acetylalanine	2

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

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

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 (17): 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)

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

4 top-level categories:

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

GO top-level categories

43 GO namespaces:

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
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
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
phosphatidylcholine acyl-chain remodeling	BP	direct assay
phosphatidylethanolamine acyl-chain remodeling	BP	direct assay
phosphatidylserine acyl-chain remodeling	BP	direct assay
endoplasmic reticulum membrane	CC	direct assay
membrane	CC	high-throughput assay
1-acylglycerophosphocholine O-acyltransferase activity	MF	direct assay
1-acylglycerophosphoethanolamine O-acyltransferase activity	MF	direct assay
1-acylglycerophosphoserine O-acyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,328 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPCAT3	ACSL4	O60488	904
LPCAT3	NCAPH2	Q6IBW4	794
LPCAT3	TAFAZZIN	Q16635	772
LPCAT3	GPX4	P36969	766
LPCAT3	AIFM2	Q9BRQ8	724
LPCAT3	NCOA4	Q13772	722
LPCAT3	LPCAT1	Q8NF37	710
LPCAT3	ALOX15	P16050	700
LPCAT3	SLC3A2	P08195	688
LPCAT3	SLC7A11	Q9UPY5	686
LPCAT3	STEAP3	Q658P3	681
LPCAT3	LPCAT2	Q7L5N7	679
LPCAT3	LPCAT4	Q643R3	659
LPCAT3	SAT1	P21673	651
LPCAT3	CARS1	P49589	641

IntAct

Human interaction partners of LPCAT3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
IFT70B	physical association	0.000	1

BioGRID (119 interactions; top human partners by supporting records): POMK (Affinity Capture-MS; 3 records), C3AR1 (Affinity Capture-MS; 2 records), CHRM4 (Affinity Capture-MS; 2 records), GYPB (Affinity Capture-MS; 2 records), HTR2C (Affinity Capture-MS; 2 records), KDELR3 (Affinity Capture-MS; 2 records), LPAR6 (Affinity Capture-MS; 2 records), OPRM1 (Affinity Capture-MS; 2 records), SLC22A16 (Affinity Capture-MS; 2 records), SLC22A6 (Affinity Capture-MS; 2 records), VTN (Affinity Capture-MS; 2 records), AGO2 (Affinity Capture-RNA), AQP3 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5J (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for LPCAT3: 10 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

ClinVar

10 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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 1,092):

Position(s)	Effect	Δscore	Sites
12:6976892	acceptor_loss	1.0000
12:6977132–6977133	donor_loss	1.0000	5
12:6977263–6977264	acceptor_loss	1.0000	6
12:6977366	donor_loss	1.0000	3
12:6977526	acceptor_gain	1.0000
12:6977526–6977527	acceptor_loss	1.0000	5
12:6978508–6978509	acceptor_loss	1.0000	3
12:6978601–6978602	donor_loss	1.0000	5
12:6978690–6978691	acceptor_loss	1.0000	5
12:6978691	acceptor_gain	1.0000

AlphaMissense

1,324 missense substitutions predicted likely pathogenic (of 3,180 scored), across 347 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M143	9	0.867	0.993
H374	8	0.996	0.999
F384	8	0.994	0.999
F439	8	0.989	0.999
N338	8	0.985	0.999
F337	8	0.982	1.000
D161	8	0.970	0.986
D138	8	0.966	0.984
D158	8	0.954	0.989
N318	8	0.948	0.997
F330	8	0.933	0.995
F203	8	0.923	0.997
H92	8	0.916	0.972
F369	8	0.910	0.986
H377	8	0.864	0.964
H428	8	0.859	0.981
F197	8	0.842	0.979
W141	7	0.996	1.000
W288	7	0.996	0.999
W373	7	0.996	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000204
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000284
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000414

Disease associations

OMIM: gene MIM:611950 | disease phenotypes:

GWAS associations

8 associations:

Study	Trait	p-value
GCST002712_13	Red blood cell fatty acid levels	3e-49
GCST002712_10	Red blood cell fatty acid levels	3e-30
GCST004621_54	Red cell distribution width	2e-17
GCST90002381_360	Eosinophil count	9e-10
GCST006018_3	Activated partial thromboplastin time	1e-9
GCST90002382_334	Eosinophil percentage of white cells	2e-9
GCST004338_3	Oleic acid (18:1n-9) levels	2e-8
GCST004747_10	Lung cancer in never smokers	9e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

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

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	decreases expression, increases 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	increases abundance, affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LPCAT3 across ~30M SureChEMBL compounds — explore on Sugi Predict.