LCAT

Summary

LCAT (lecithin-cholesterol acyltransferase, HGNC:6522) is a protein-coding gene on chromosome 16q22.1, encoding Phosphatidylcholine-sterol acyltransferase (P04180). Central enzyme in the extracellular metabolism of plasma lipoproteins.

This gene encodes the extracellular cholesterol esterifying enzyme, lecithin-cholesterol acyltransferase. The esterification of cholesterol is required for cholesterol transport. Mutations in this gene have been found to cause fish-eye disease as well as LCAT deficiency.

Source: NCBI Gene 3931 — RefSeq curated summary.

At a glance

• Gene–disease (curated): LCAT deficiency (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 360 total — 19 pathogenic, 16 likely-pathogenic (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 27 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 21
• Constraint (gnomAD): pLI 0.77 (intermediate), LOEUF 0.57 (moderately constrained)
• MANE Select transcript: NM_000229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6522
Approved symbol	LCAT
Name	lecithin-cholesterol acyltransferase
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213398
Ensembl biotype	protein_coding
OMIM	606967
Entrez	3931

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 18 protein_coding, 14 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000264005

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

ENST00000264005, ENST00000570369, ENST00000570396, ENST00000570980, ENST00000573538, ENST00000573846, ENST00000575277, ENST00000575467, ENST00000576450, ENST00001003199, ENST00001003200, ENST00001003201, ENST00001003202, ENST00001003203, ENST00001003204, ENST00001003205, ENST00001003207, ENST00001003208, ENST00001003209, ENST00001003210, ENST00001003211, ENST00001003212, ENST00001003213, ENST00001003214, ENST00001003215, ENST00001003216, ENST00001003217, ENST00001003218, ENST00001003219, ENST00001003220, ENST00001094580, ENST00001120015, ENST00001120016, ENST00001136544

RefSeq mRNA: 1 — MANE Select: NM_000229 NM_000229

CCDS: CCDS10854

Canonical transcript exons

ENST00000264005 — 6 exons

Exon	Start	End
ENSE00000692168	67943056	67943212
ENSE00001308070	67939750	67940478
ENSE00003478042	67942671	67942766
ENSE00003564538	67942861	67942976
ENSE00003600601	67942363	67942587
ENSE00003893923	67943948	67944120

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 99.12.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4337 / max 324.4416, expressed in 183 samples.

Highest expression (Bgee): lobe of liver, hemisphere of cerebellum, tibial nerve, lobe of thyroid gland, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LCAT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	2.2e-23	+0.29	16:67956073:C:A
Adipose Subcutaneous	eqtl	7.6e-20	+0.26	16:67939268:C:T
Whole Blood	eqtl	1.8e-19	+0.28	16:68030569:T:C
Cells Cultured fibroblasts	eqtl	3.7e-18	+0.21	16:67939268:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-16	+0.29	16:67959740:T:C
Skin Sun Exposed Lower leg	eqtl	1.3e-15	+0.28	16:67956073:C:A
Artery Tibial	eqtl	1.4e-14	+0.22	16:67943479:T:C
Muscle Skeletal	eqtl	4.1e-12	+0.25	16:67956073:C:A
Adipose Visceral Omentum	eqtl	1.6e-08	+0.18	16:67840361:T:C
Heart Atrial Appendage	eqtl	3.7e-08	+0.16	16:67955620:T:C
Testis	eqtl	6.0e-08	+0.24	16:68058947:G:C
Breast Mammary Tissue	eqtl	5.6e-07	+0.19	16:67943479:T:C
Thyroid	eqtl	1.9e-06	+0.16	16:67933975:A:C
Esophagus Muscularis	eqtl	6.6e-06	+0.11	16:67784351:A:G
Spleen	eqtl	1.6e-05	+0.24	16:67979568:T:C
Heart Left Ventricle	eqtl	1.6e-04	+0.12	16:67933975:A:C
Colon Transverse	eqtl	2.4e-04	+0.12	16:67807226:T:G
Artery Aorta	eqtl	3.5e-04	+0.14	16:67939268:C:T
Esophagus Gastroesophageal Junction	eqtl	7.5e-04	+0.12	16:67807226:T:G
Cells EBV-transformed lymphocytes	eqtl	8.8e-04	+0.25	16:67983446:CA:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
157834	1.4337	183

Top tissues by expression

showing 100 of 280 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.16	gold quality
tibial nerve	UBERON:0001323	96.14	gold quality
left lobe of thyroid gland	UBERON:0001120	96.11	gold quality
apex of heart	UBERON:0002098	96.05	gold quality
liver	UBERON:0002107	96.01	gold quality
right lobe of thyroid gland	UBERON:0001119	95.80	gold quality
ascending aorta	UBERON:0001496	95.68	gold quality
right coronary artery	UBERON:0001625	95.64	gold quality
thoracic aorta	UBERON:0001515	95.55	gold quality
endocervix	UBERON:0000458	95.54	gold quality
body of uterus	UBERON:0009853	95.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.13	gold quality
lower esophagus	UBERON:0013473	95.10	gold quality
left coronary artery	UBERON:0001626	94.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.92	gold quality
right lung	UBERON:0002167	94.81	gold quality
cerebellar hemisphere	UBERON:0002245	94.78	gold quality
descending thoracic aorta	UBERON:0002345	94.76	gold quality
upper lobe of left lung	UBERON:0008952	94.76	gold quality
cerebellar cortex	UBERON:0002129	94.66	gold quality
metanephros cortex	UBERON:0010533	94.49	gold quality
left uterine tube	UBERON:0001303	94.45	gold quality
aorta	UBERON:0000947	94.33	gold quality
thyroid gland	UBERON:0002046	94.30	gold quality
omental fat pad	UBERON:0010414	94.07	gold quality
coronary artery	UBERON:0001621	94.03	gold quality
peritoneum	UBERON:0002358	93.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.89	gold quality
mucosa of stomach	UBERON:0001199	93.83	gold quality
popliteal artery	UBERON:0002250	93.69	gold quality
tibial artery	UBERON:0007610	93.69	gold quality
ectocervix	UBERON:0012249	93.46	gold quality
cerebellum	UBERON:0002037	93.39	gold quality
right ovary	UBERON:0002118	93.20	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.07	gold quality
right atrium auricular region	UBERON:0006631	93.05	gold quality
left ovary	UBERON:0002119	92.96	gold quality
skin of abdomen	UBERON:0001416	92.91	gold quality
upper lobe of lung	UBERON:0008948	92.74	gold quality
skin of leg	UBERON:0001511	92.54	gold quality
heart left ventricle	UBERON:0002084	92.00	gold quality
adenohypophysis	UBERON:0002196	91.57	gold quality
stromal cell of endometrium	CL:0002255	91.51	gold quality
right adrenal gland	UBERON:0001233	91.29	gold quality
right adrenal gland cortex	UBERON:0035827	91.24	gold quality
minor salivary gland	UBERON:0001830	91.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.17	gold quality
lower esophagus mucosa	UBERON:0035834	91.14	gold quality
cardiac ventricle	UBERON:0002082	91.11	gold quality
cardiac atrium	UBERON:0002081	90.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.84	gold quality
right uterine tube	UBERON:0001302	90.64	gold quality
left adrenal gland cortex	UBERON:0035825	90.51	gold quality
left adrenal gland	UBERON:0001234	90.37	gold quality
body of pancreas	UBERON:0001150	90.27	gold quality
paraflocculus	UBERON:0005351	89.79	gold quality
esophagus	UBERON:0001043	89.70	gold quality
heart	UBERON:0000948	89.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.46	gold quality
body of stomach	UBERON:0001161	89.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.27	gold quality
spleen	UBERON:0002106	89.11	gold quality
adrenal cortex	UBERON:0001235	89.00	gold quality
sural nerve	UBERON:0015488	88.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.60	gold quality
zone of skin	UBERON:0000014	88.50	gold quality
transverse colon	UBERON:0001157	88.14	gold quality
pituitary gland	UBERON:0000007	88.08	gold quality
vagina	UBERON:0000996	87.99	gold quality
adrenal gland	UBERON:0002369	87.87	gold quality
adipose tissue	UBERON:0001013	87.33	gold quality
prostate gland	UBERON:0002367	87.27	gold quality
mouth mucosa	UBERON:0003729	86.94	gold quality
granulocyte	CL:0000094	86.84	gold quality
spinal cord	UBERON:0002240	86.77	gold quality
gastrocnemius	UBERON:0001388	86.75	gold quality
gall bladder	UBERON:0002110	86.73	gold quality
ventricular zone	UBERON:0003053	86.62	gold quality
right frontal lobe	UBERON:0002810	86.55	gold quality
connective tissue	UBERON:0002384	86.41	gold quality
muscle of leg	UBERON:0001383	86.30	gold quality
stomach	UBERON:0000945	86.15	gold quality
saliva-secreting gland	UBERON:0001044	86.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.80	gold quality
esophagus mucosa	UBERON:0002469	85.78	gold quality
ovary	UBERON:0000992	85.77	gold quality
mucosa of transverse colon	UBERON:0004991	85.69	gold quality
fundus of stomach	UBERON:0001160	85.57	gold quality
small intestine	UBERON:0002108	85.23	gold quality
left testis	UBERON:0004533	84.84	gold quality
amygdala	UBERON:0001876	84.81	gold quality
right testis	UBERON:0004534	84.66	gold quality
sigmoid colon	UBERON:0001159	84.29	gold quality
myometrium	UBERON:0001296	83.88	gold quality
cingulate cortex	UBERON:0003027	83.23	gold quality
anatomical system	UBERON:0000467	83.18	gold quality
anterior cingulate cortex	UBERON:0009835	83.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.96	gold quality
multicellular organism	UBERON:0000468	82.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.57

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Liver	tissue	191.4
Cerebellum	tissue	60.8
Choroid plexus	tissue	41.8
Frontal cortex	tissue	41.5
Periaqueductal gray	tissue	35.7
Substantia nigra	tissue	31.5
Skin 1	tissue	30.2
Midbrain	tissue	29.3
Medulla oblongata	tissue	27.6
Caudate putamen	tissue	27.2
Vagina	tissue	26.5
Thalamus	tissue	26.3
Pons	tissue	25.7
Spinal cord	tissue	24.2
Superior colliculi	tissue	23.3
Hippocampus	tissue	20.7
Hippocampal formation	tissue	19.8
Locus coeruleus	tissue	18.9
Seminal vesicle	tissue	17.6
Pituitary gland	tissue	17.5
Cerebral cortex	tissue	17.4
Occipital cortex	tissue	17.4
Somatosensory cortex	tissue	16.8
Placenta	tissue	16.7
Lung	tissue	16.5
Endometrium 1	tissue	16.3
Postcentral gyrus	tissue	15.8
Hypothalamus	tissue	15.3
Nucleus accumbens	tissue	14.6
Heart muscle	tissue	14.4
Amygdala	tissue	14.3
Adipose tissue	tissue	13.9
Septum	tissue	13.9
Motor cortex	tissue	13.6
Putamen	tissue	13.6
Temporal cortex	tissue	13.6
Prefrontal cortex	tissue	12.9
Entorhinal cortex	tissue	12.9
Spleen	tissue	12.8
Basal ganglia	tissue	12.7
Thyroid gland	tissue	12.5
Retrosplenial and cingulate cortex	tissue	12.4
Retrosplenial cortex	tissue	12.0
Skeletal muscle	tissue	11.9
Smooth muscle	tissue	11.5
Insular cortex	tissue	11.4
Adrenal gland	tissue	11.1
Gallbladder	tissue	10.8
Ventral forebrain	tissue	10.7
Corpus callosum	tissue	10.4
Prostate	tissue	10.3
Olfactory bulb	tissue	10.2
Ovary	tissue	9.6
Thymus	tissue	8.8
Epididymis	tissue	8.6
Pancreas	tissue	8.3
Tongue	tissue	8.3
Appendix	tissue	7.8
Parathyroid gland	tissue	7.6
Cervix	tissue	7.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Cerebellar cortex (81.7), Flocculonodular lobe (73.0), Vermis (70.3), Area postrema (50.9), Blood vessel (34.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX3, SP1, SP3, STAT3

Functional genomics

gnomAD constraint: pLI 0.765, LOEUF 0.568, missense Z 2.37 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000264005 — one region, missense o/e 0.75.

Literature-anchored findings (GeneRIF, showing 40)

• The lecithin:cholesterol acyltransferase (LCAT) activity in cord blood was extremely low. (PMID:11882335)
• Results suggest that LCAT may take part in the detoxification of oxidants even after the loss of its cholesterol esterification function. (PMID:11966470)
• IL-6 induced activation of full-length LCAT promoter activity. A minimal IL-6 response element mapped within the distal promoter and was sufficient to mediate the IL-6 response (PMID:12032172)
• In conclusion, 12% of Hypoalphalipoproteinemia subjects were found to carry mutations in apo A-I, LCAT, or GBA genes (PMID:12048121)
• The results suggest that as follicle maturation progresses, Toc and Asc concentrations increase in follicular fluid, thus protecting LCAT from oxidative damage and loss of activity (PMID:12051518)
• Endotoxin-lipoprotein complex formation as a factor in atherogenesis: associations with hyperlipidemia and with lecithin:cholesterol acyltransferase activity (PMID:12139471)
• comparison of 5 natural point mutations of apo A-I illustrates that a specific sequence between amino acids 110 and 162 is required for LCAT activation (PMID:12573451)
• 608T polymorphism of LCAT gene was associated with higher plasma HDL-C level in Coronary Arteriosclerosis patients. (PMID:12673583)
• Familial lecithin:cholesterol acyltransferase (LCAT) deficiency, arising from mutation, is associated with complete absence of Lecithin:cholesterol acyltransferase (LCAT) activity. (PMID:12957688)
• Postprandial chylomicrons may play an important role in promoting reverse cholesterol transport in vivo by serving as the preferred ultimate vehicle for transporting cholesterol released from cell membranes to the liver via LCAT and CETP. (PMID:15102891)
• T13M mutation of LCAT gene causes fish-eye disease. (PMID:15115696)
• tested whether rare sequence variants of ABCA1, APOA1, and LCAT collectively contribute to variation in plasma levels of high density lipoprotein cholesterol; nonsynonymous sequence variants were significantly more common in individuals with low HDL-C (PMID:15297675)
• role of LCAT in estradiol-2 esterification and its involvement in antioxidant protection of HDL (PMID:15472210)
• Selective LCAT-mediated reactivity with pre-beta 1-high density lipoprotein represents a novel mechanism increasing the efficiency of reverse cholesterol transport. (PMID:15544352)
• Deficiency is manifested by fish eye disease. (PMID:15936482)
• the inheritance of a mutated LCAT genotype causes a gene-dose-dependent alteration in the plasma lipid/lipoprotein profile, which is remarkably similar between subjects classified as LCAT deficiency or fish eye disease (PMID:15994445)
• a novel G–>A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine in familial LCAT deficiency (PMID:16051254)
• Mutation underlies increased carotid artery intima-media thickness, which suggests that LCAT protects against atherosclerosis. (PMID:16061733)
• analysis of mutations in the LCAT gene that result in an intermediate phenotype between LCAT-deficiency and fish-eye disease (case report) (PMID:16216249)
• Decreased LDL in LCAT-deficiency is attributable to increased catabolism caused by rapid catabolism of abnormal LDL and upregulation of LDL receptor pathway. Decreased catabolism of LpX contributes to its accumulation in LCAT-deficiency. (Lipoprotein X) (PMID:16543491)
• Redistribution of charged residues in mutant LCAT may be a major factor responsible for the dramatically reduced activity of the enzyme with HDL and reconstituted high density lipoprotein (rHDL). (PMID:16780378)
• The LCAT 608C/T polymorphism is possibly a predisposing factor in atherosclerotic cerebral infarction happening of Chinese Han population. (PMID:16883530)
• HDL particles generated by this pathway may account at least for some of the atheroprotective functions of apolipoprotein E (PMID:17206937)
• Apolipoprotein A=I activation affects the kinetics of the LCAT reaction (PMID:17216278)
• decreased cholesterol-total cholesterol ratio in the plasma of human apolipoprotein A-I transgenic Scavenger Receptors, Class B, Type I-/- mice is attributed to a reduction in LCAT reactivity with sphingomyelin-enriched HDL particles (PMID:17272829)
• analysis of mutations in LCAT in two patients with severe LCAT deficiency [case report] (PMID:17526537)
• The study establishes that apoA-I(Leu141Arg)Pisa and apoA-I(Leu159Arg)FIN inhibit an early step in the biogenesis of HDL due to inefficient esterification of the cholesterol of the prebeta1-HDL particles by the endogenous LCAT. (PMID:17711302)
• Multiple linear regression analysis confirmed the independent association of cellular cholesterol efflux to plasma with cholesteryl ester transfer protein genotype (PMID:18178167)
• Analysis of the LCAT gene showed two novel point mutations in exon 2 and exon 3, leading to amino acid substitution. As far, these mutations have not been reported in FLD or FED patients. (PMID:18397721)
• HbA1c provides an easy-to-assess, accurate measure of LCAT activity in type 2 diabetes. (PMID:18485513)
• oxidation of a single Met in apoA-I results in impaired LCAT activation (PMID:18719109)
• Plasma LCAT activity is elevated in metabolic syndrome and may be a marker of subclinical atherosclerosis (PMID:18782872)
• Functional LCAT is not required for macrophage cholesterol efflux to human serum. (PMID:18922527)
• Recent research findings from animal and human studies have revealed a potential beneficial role of LCAT in reducing atherosclerosis–REVIEW (PMID:19306528)
• Suggest that a LCAT-/- genotype associated with an APOE epsilon2 allele could be a novel mechanism leading to dysbetalipoproteinemia in familial LCAT deficient patients. (PMID:19515369)
• Low LCAT plasma levels are not associated with increased atherosclerosis in the general population. (PMID:19671930)
• Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density lipoprotein cholesterol levels. (PMID:19687369)
• lecithin:cholesterol acyltransferase activity is not responsible for low incidence of cardiovascular events (PMID:19698944)
• Plasma lecithin: cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men. (PMID:19800416)
• Novel N-terminal mutation of human apolipoprotein A-I reduces self-association and impairs LCAT activation (PMID:20884842)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lcat	ENSDARG00000099424
mus_musculus	Lcat	ENSMUSG00000035237
rattus_norvegicus	Lcat	ENSRNOG00000019573

Paralogs (1): PLA2G15 (ENSG00000103066)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96755) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 24 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating HDL cholesterol level	4
abnormal lipid level	3
decreased circulating cholesterol level	3
increased circulating triglyceride level	2
abnormal lipid homeostasis	2
abnormal cholesterol homeostasis	2
abnormal renal glomerulus morphology	2
abnormal circulating protein level	2
expanded mesangial matrix	2
increased mesangial cell number	2
abnormal adrenal gland morphology	1
increased circulating HDL cholesterol level	1
hemolytic anemia	1
reticulocytosis	1
increased urine protein level	1
increased circulating phospholipid level	1
increased cholesterol level	1
decreased cholesterol level	1
decreased circulating VLDL cholesterol level	1
increased circulating cholesterol level	1
glomerulosclerosis	1
abnormal circulating phospholipid level	1
abnormal kidney afferent arteriole morphology	1
decreased erythrocyte osmotic fragility	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
Papio anubis	Q08758	98.4%	Diamond
Oryctolagus cuniculus	P53761	92.7%	Diamond
Canis lupus familiaris	Q6XPZ3	90.5%	Diamond
Myodes glareolus	O35502	89.3%	Diamond
Gerbilliscus gambianus	O35840	89.3%	Diamond
Micromys minutus	O35724	87.8%	Diamond
Bos taurus	Q8WMP9	84.7%	Diamond
Eliomys quercinus	O35573	83.7%	Diamond
Gallus gallus	P53760	74.0%	Diamond
Sus scrofa	P30930	44.4%	Diamond
Arabidopsis thaliana	Q9FZI8	40.6%	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
DPEP2	protein-coding	64174
DPEP3	protein-coding	64180
SLC12A4	protein-coding	6560
PSMB10	protein-coding	5699
NRN1L	protein-coding	123904
CTRL	protein-coding	1506
PSKH1	protein-coding	5681
DPEP2NB	protein-coding	100131303
EDC4	protein-coding	23644

Protein

Protein identifiers

Phosphatidylcholine-sterol acyltransferase — P04180 (reviewed: P04180)

Alternative names: 1-alkyl-2-acetylglycerophosphocholine esterase, Lecithin-cholesterol acyltransferase, Phospholipid-cholesterol acyltransferase, Platelet-activating factor acetylhydrolase

All UniProt accessions (8): P04180, A0A140VK24, I3L0J6, I3L1Q6, I3L215, I3L3R0, J3QKT0, J3QSE5

UniProt curated annotations — full annotation on UniProt →

Function. Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs). The cholesterol ester is then transported back to the liver. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms. Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF. Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters.

Subcellular location. Secreted.

Tissue specificity. Detected in blood plasma. Detected in cerebral spinal fluid (at protein level). Detected in liver. Expressed mainly in brain, liver and testes.

Post-translational modifications. O- and N-glycosylated. O-glycosylation on Thr-431 and Ser-433 consists of sialylated galactose beta 1–>3N-acetylgalactosamine structures. N-glycosylated sites contain sialylated triantennary and/or biantennary complex structures.

Disease relevance. Lecithin-cholesterol acyltransferase deficiency (LCATD) [MIM:245900] A disorder of lipoprotein metabolism characterized by inadequate esterification of plasmatic cholesterol. Two clinical forms are recognized: complete LCAT deficiency and fish-eye disease. LCATD is generally referred to the complete form which is associated with absence of both alpha and beta LCAT activities resulting in esterification anomalies involving both HDL (alpha-LCAT activity) and LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure. The disease is caused by variants affecting the gene represented in this entry. Fish-eye disease (FED) [MIM:136120] A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea (‘fish-eye’). The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4. Inhibited by haptoglobin and 5,5’-dithiobis-(2-nitrobenzoic acid) (DTNB).

Miscellaneous. Levels of LCAT activity correlates inversely with leptin levels as well as with obesity for a wide range of BMI values.

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

RefSeq proteins (1): NP_000220* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003386	LACT/PDAT_acylTrfase	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF02450

Enzyme classification (BRENDA)

• EC 2.3.1.43 — phosphatidylcholine-sterol O-acyltransferase (BRENDA: 17 organisms, 163 substrates, 53 inhibitors, 25 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1,2-BIS-(1-PYRENEBUTANOYL)-SN-GLYCERO-3-PHOSPHOC	0.14–20.5	6
1-PALMITOYL-2-OLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0006–0.027	3
CHOLESTEROL	0.57–21.4	3
PHOSPHATIDYLCHOLINE	—	2
1,2-BIS[4-(1-PYRENO)BUTANOYL]-SN-GLYCERO-3-PHOSP	0.0006	1
APOLIPOPROTEIN-A-I	0.0001	1
DEHYDROERGOSTEROL	0.003	1

Catalyzed reactions (Rhea)

• a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:17777)
• a sterol + a 1,2-diacyl-sn-glycero-3-phosphocholine = a sterol ester + a 1-acyl-sn-glycero-3-phosphocholine (RHEA:21204)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40427)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:40811)
• a 1-hexadecanoyl-2-acyl-sn-glycero-3-phosphocholine + (24S)-hydroxycholesterol = (24S)-24-hydroxycholesterol ester + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:43216)
• (24S)-hydroxycholesterol + 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine = (24S)-hydroxycholesterol 3-linoleoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:43224)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + cholesterol = cholesteryl (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:53448)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + cholesterol = cholesteryl (9Z-octadecenoate) + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:53456)
• 1-hexadecanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = cholesteryl (5Z,8Z,11Z)-eicosatrienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:53460)
• 1-hexadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = cholesteryl (8Z,11Z,14Z)-eicosatrienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:53464)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine + cholesterol = (5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:53468)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + cholesterol = cholesteryl (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:53472)

UniProt features (113 total): sequence variant 44, helix 19, strand 19, turn 11, glycosylation site 6, mutagenesis site 5, active site 3, disulfide bond 2, signal peptide 1, chain 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
5BV7	Crystal structure of human LCAT (L4F, N5D) in complex with Fab of an agonistic antibody	X-RAY DIFFRACTION	2.45
4XWG	Crystal Structure of LCAT (C31Y) in complex with Fab1	X-RAY DIFFRACTION	2.65
5TXF	Crystal structure of Lecithin:cholesterol acyltransferase (LCAT) in a closed conformation	X-RAY DIFFRACTION	3.1
6MVD	Crystal structure of Lecithin:cholesterol acyltransferase (LCAT) in complex with …	X-RAY DIFFRACTION	3.1
4XX1	Low resolution structure of LCAT in complex with Fab1	X-RAY DIFFRACTION	3.6
4X96	Low resolution crystal structure of Lecithin:Cholesterol Acyltransferase (LCAT; residues …	X-RAY DIFFRACTION	8.69
9MXZ	Lecithin:Cholesterol Acyltransferase Bound to Apolipoprotein A-I dimer in HDL	ELECTRON MICROSCOPY	9.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04180-F1	87.33	0.73

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 4XWG, 4XX1, 5BV7

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Hydrolases, Metabolic proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IF approved

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 (4)

Position	Role
205	nucleophile
369	charge relay system
401	charge relay system
173	determinant for substrate specificity

Disulfide bonds (2)

Type	Positions
Disulfide bond	74–98, 337–380

Glycosylation sites (6)

Type	Positions
O-linked (galnac…) threonine	431
O-linked (galnac…) serine	433
N-linked (glcnac…) (complex) asparagine	44, 108, 296, 408

Mutagenesis-validated functional residues (5)

Position	Phenotype
173	increased activity towards papc. increased papc/popc activity ratio.
173	little change in enzyme specific activity nor in papc/popc activity ratio.
173	decreased enzyme specific activity. increased papc/popc activity ratio.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-8964058	HDL remodeling	curated
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance	—
R-HSA-8963899	Plasma lipoprotein remodeling	—
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 239 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, chr16q22, GOBP_STEROL_HOMEOSTASIS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GNF2_GSTM1, GOBP_RESPONSE_TO_CORTICOSTEROID, LFA1_Q6, GNF2_HPN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_COPPER_ION, GOBP_PROTEIN_LIPID_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (15): lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644), phosphatidylcholine biosynthetic process (GO:0006656), cholesterol metabolic process (GO:0008203), cholesterol transport (GO:0030301), very-low-density lipoprotein particle remodeling (GO:0034372), high-density lipoprotein particle remodeling (GO:0034375), lipoprotein metabolic process (GO:0042157), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), phosphatidylcholine metabolic process (GO:0046470), response to copper ion (GO:0046688), response to glucocorticoid (GO:0051384), regulation of high-density lipoprotein particle assembly (GO:0090107), steroid metabolic process (GO:0008202)

GO Molecular Function (10): 1-alkyl-2-acetylglycerophosphocholine esterase activity (GO:0003847), phosphatidylcholine-sterol O-acyltransferase activity (GO:0004607), A2-type glycerophospholipase activity (GO:0004623), sterol ester esterase activity (GO:0004771), apolipoprotein A-I binding (GO:0034186), platelet-activating factor acetyltransferase activity (GO:0047179), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), hydrolase activity (GO:0016787)

GO Cellular Component (3): extracellular region (GO:0005576), high-density lipoprotein particle (GO:0034364), extracellular exosome (GO:0070062)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Plasma lipoprotein remodeling	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

31 GO namespaces:

Category	Terms
carboxylic ester hydrolase activity	3
lipid metabolic process	2
catalytic activity	2
primary metabolic process	1
organophosphate metabolic process	1
phosphatidylcholine metabolic process	1
glycerophospholipid biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
sterol transport	1
triglyceride-rich lipoprotein particle remodeling	1
plasma lipoprotein particle remodeling	1
protein metabolic process	1
sterol homeostasis	1
cholesterol transport	1
glycerophospholipid metabolic process	1
response to metal ion	1
response to corticosteroid	1
high-density lipoprotein particle assembly	1
regulation of protein-containing complex assembly	1
regulation of multicellular organismal process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
glycerophospholipase activity	1
lipase activity	1
apolipoprotein binding	1
acetyltransferase activity	1
binding	1
transferase activity	1
cellular anatomical structure	1
plasma lipoprotein particle	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
cholesterol homeostasis	BP	direct assay
cholesterol metabolic process	BP	direct assay
cholesterol transport	BP	direct assay
high-density lipoprotein particle remodeling	BP	direct assay
phosphatidylcholine biosynthetic process	BP	direct assay
phosphatidylcholine metabolic process	BP	direct assay
phospholipid metabolic process	BP	direct assay
reverse cholesterol transport	BP	direct assay
very-low-density lipoprotein particle remodeling	BP	direct assay
extracellular exosome	CC	high-throughput assay
high-density lipoprotein particle	CC	direct assay
1-alkyl-2-acetylglycerophosphocholine esterase activity	MF	direct assay
apolipoprotein A-I binding	MF	physical interaction
phosphatidylcholine-sterol O-acyltransferase activity	MF	direct assay
platelet-activating factor acetyltransferase activity	MF	direct assay
sterol ester esterase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,482 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCAT	APOA1	P02647	952
LCAT	CETP	P11597	923
LCAT	APOB	P04114	875
LCAT	APOA2	P02652	850
LCAT	ABCA1	O95477	849
LCAT	PSKH1	P11801	821
LCAT	PON1	P27169	819
LCAT	SCARB1	Q8WTV0	781
LCAT	APOC3	P02656	779
LCAT	LPL	P06858	768
LCAT	LIPC	P11150	763
LCAT	PSMB10	P40306	758
LCAT	PLTP	P55058	737
LCAT	NPC1L1	Q9UHC9	689
LCAT	APOE	P02649	675

IntAct

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

2 partners by confidence:

Partner	Interaction type	MIscore	Records
APOA1	direct interaction	0.620	2
WFS1	physical association	0.560	3

BioGRID (14 interactions; top human partners by supporting records): APOA1 (Reconstituted Complex; 7 records), A2M (Affinity Capture-Western; 2 records), APOA2 (Co-purification), APOE (Biochemical Activity), EXOSC10 (Two-hybrid), PARP3 (Proximity Label-MS), PIKFYVE (Co-crystal Structure)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
APOA1	“up-regulates activity”	LCAT	binding

Disease & clinical

Genetic variants

Variant evidence for LCAT: 360 ClinVar records (35 pathogenic / likely pathogenic); 21 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	16
Uncertain significance	146
Likely benign	134
Benign	8

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 35 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3660	NM_000229.2(LCAT):c.440C>T (p.Thr147Ile)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
3661	NM_000229.2(LCAT):c.101dup (p.His35fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
3662	NM_000229.2(LCAT):c.101C>T (p.Pro34Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
632262	NM_000229.2(LCAT):c.367C>T (p.Arg123Cys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
1764448	NM_000229.2(LCAT):c.1267C>T (p.Arg423Cys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2631093	NM_000229.2(LCAT):c.160G>A (p.Gly54Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3581220	NM_000229.2(LCAT):c.115A>T (p.Lys39Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
626357	NM_000229.2(LCAT):c.997G>A (p.Val333Met)	Pathogenic	criteria provided, single submitter	1
626358	NM_000229.2(LCAT):c.1210A>G (p.Met404Val)	Pathogenic	criteria provided, single submitter	1
1969478	NM_000229.2(LCAT):c.23G>A (p.Trp8Ter)	Pathogenic	criteria provided, single submitter	1
2736369	NM_000229.2(LCAT):c.803G>A (p.Arg268His)	Pathogenic	criteria provided, single submitter	1
2879462	NM_000229.2(LCAT):c.849G>A (p.Trp283Ter)	Pathogenic	criteria provided, single submitter	1
3581207	NM_000229.2(LCAT):c.511C>T (p.Arg171Trp)	Pathogenic	criteria provided, single submitter	1
3668	NM_000229.2(LCAT):c.475C>T (p.Arg159Trp)	Likely pathogenic	criteria provided, single submitter	2
1338728	NM_000229.2(LCAT):c.802C>T (p.Arg268Cys)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore LCAT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 561):

Position(s)	Effect	Δscore	Sites
16:67940479–67940480	acceptor_loss	1.0000	2
16:67942669–67942670	donor_loss	1.0000	3
16:67942859–67942860	donor_loss	1.0000	4
16:67942977–67942978	acceptor_loss	1.0000	5
16:67943054–67943055	donor_loss	1.0000	5
16:67940479–67940480	acceptor_loss	0.9900	3
16:67942361–67942362	donor_loss	0.9900	5
16:67942588–67942589	acceptor_loss	0.9900	6
16:67942669–67942670	donor_loss	0.9900	2
16:67942767–67942768	acceptor_loss	0.9900	4

AlphaMissense

951 missense substitutions predicted likely pathogenic (of 2,864 scored), across 255 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
D369	8	0.976	0.995
D169	8	0.967	0.986
H401	8	0.965	0.980
H204	8	0.954	0.983
S205	8	0.950	0.997
F127	8	0.929	0.993
D101	8	0.833	0.966
D137	8	0.811	0.904
C98	7	0.995	0.998
C74	7	0.993	0.998
W170	7	0.975	0.995
W85	7	0.972	0.995
C380	7	0.965	0.982
W222	7	0.962	0.990
C337	7	0.956	0.990
W99	7	0.950	0.992
F355	7	0.929	0.976
W383	7	0.926	0.986
F406	7	0.922	0.984
E134	7	0.917	0.972

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Liver Hepatocellular Carcinoma)

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	favorable	1.68e-07
Liver Hepatocellular Carcinoma (validation)	favorable	0.000105
Skin Cutaneous Melanoma (TCGA)	unfavorable	0.000138
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000762

Disease associations

OMIM: gene MIM:606967 | disease phenotypes: MIM:245900, MIM:136120

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
LCAT deficiency	Definitive	Autosomal recessive
fish eye disease	Definitive	Autosomal recessive	4
Norum disease	Strong	Autosomal recessive	2

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Bilateral congenital or childhood onset cataracts	green
Corneal dystrophy	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Proteinuric renal disease	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Unexplained young onset end-stage renal disease	green

Mondo (3): Norum disease (MONDO:0009515), fish eye disease (MONDO:0007620), LCAT deficiency (MONDO:0018999)

Orphanet (3): Familial LCAT deficiency (Orphanet:79293), LCAT deficiency (Orphanet:650), Fish-eye disease (Orphanet:79292)

HPO phenotypes

21 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000505	Visual impairment
HP:0001084	Corneal arcus
HP:0001681	Angina pectoris
HP:0001744	Splenomegaly
HP:0001878	Hemolytic anemia
HP:0001895	Normochromic anemia
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002621	Atherosclerosis
HP:0002716	Lymphadenopathy
HP:0003141	Elevated circulating LDL-C concentration
HP:0003233	Decreased circulating HDL-C concentration
HP:0003362	Elevated circulating VLDL-C concentration
HP:0003581	Adult onset
HP:0003651	Foam cells
HP:0007759	Opacification of the corneal stroma
HP:0007957	Corneal opacity
HP:0025433	Decreased lecithin cholesterol acyl transferase level

GWAS associations

21 associations:

Study	Trait	p-value
GCST004232_69	HDL cholesterol levels	3e-57
GCST002223_17	HDL cholesterol	8e-54
GCST000755_31	HDL cholesterol	8e-33
GCST90002397_652	Mean spheric corpuscular volume	2e-32
GCST002899_8	HDL cholesterol	9e-26
GCST008035_12	High density lipoprotein cholesterol levels	2e-16
GCST90002403_52	Red blood cell count	1e-15
GCST006614_140	Total cholesterol levels	1e-14
GCST010002_165	Refractive error	2e-14
GCST000290_13	HDL cholesterol	9e-13
GCST000974_6	HDL cholesterol	2e-11
GCST007850_6	HDL cholesterol	2e-10
GCST004234_11	HDL cholesterol levels	4e-10
GCST005446_23	Total cholesterol levels in HDL	6e-10
GCST004232_35	HDL cholesterol levels	3e-9
GCST002539_44	Schizophrenia	2e-8
GCST000284_3	HDL cholesterol	3e-8
GCST006803_78	Schizophrenia	4e-8
GCST000135_8	HDL cholesterol	1e-7
GCST000805_12	HDL cholesterol	2e-7
GCST008035_13	High density lipoprotein cholesterol levels	1e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5942 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

5 measured of 6 human assays (6 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(+)-4,5-Dihydroxy-4-(trifluoromethyl)-3-{1-[5-(trifluoromethyl)pyrazin-2-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one	EC50	4 nM	US-10138240: Crystal of 5-hydroxy-4-(trifluoromethyl)pyrazolopyridine derivative
(+)-cis-5-Hydroxy-4-(trifluoromethyl)-3-{1-[2-(trifluoromethyl)pyrimidin-5-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one	EC50	18 nM	US-10138240: Crystal of 5-hydroxy-4-(trifluoromethyl)pyrazolopyridine derivative
Difluoroketone phospholipid analogue, 3	IC50	28 nM
Difluoroketone phospholipid analogue, 2	IC50	60 nM
Difluoroketone phospholipid analogue, 4	IC50	60 nM

ChEMBL bioactivities

152 potent at pChembl≥5 of 152 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	EC50	4	nM	CHEMBL4571766
8.40	EC50	4	nM	CHEMBL4444702
8.15	EC50	7	nM	CHEMBL4543681
8.15	EC50	7	nM	CHEMBL4444091
8.15	EC50	7	nM	CHEMBL4567833
8.10	EC50	8	nM	CHEMBL4449961
8.05	EC50	9	nM	CHEMBL4438875
7.96	EC50	11	nM	CHEMBL4565710
7.92	EC50	12	nM	CHEMBL4565889
7.89	EC50	13	nM	CHEMBL4475628
7.89	EC50	13	nM	CHEMBL4449770
7.89	EC50	13	nM	CHEMBL4444770
7.82	EC50	15	nM	CHEMBL4462753
7.75	EC50	18	nM	CHEMBL4438084
7.75	EC50	18	nM	CHEMBL4435610
7.75	EC50	18	nM	CHEMBL4592989
7.75	EC50	18	nM	CHEMBL4463860
7.70	EC50	20	nM	CHEMBL4453452
7.68	EC50	21	nM	CHEMBL4438084
7.68	EC50	21	nM	CHEMBL4455643
7.68	EC50	21	nM	CHEMBL4445217
7.66	EC50	22	nM	CHEMBL4567833
7.64	EC50	23	nM	CHEMBL4443799
7.64	EC50	23	nM	CHEMBL4445235
7.62	EC50	24	nM	CHEMBL4456783
7.58	EC50	26	nM	CHEMBL4442211
7.57	EC50	27	nM	CHEMBL4445217
7.57	EC50	27	nM	CHEMBL4541184
7.57	EC50	27	nM	CHEMBL4435684
7.54	EC50	29	nM	CHEMBL4514555
7.52	EC50	30	nM	CHEMBL4536836
7.51	EC50	31	nM	CHEMBL4483570
7.51	EC50	31	nM	CHEMBL4563848
7.50	EC50	32	nM	CHEMBL4575561
7.50	EC50	32	nM	CHEMBL4461575
7.47	EC50	34	nM	CHEMBL4450717
7.46	EC50	35	nM	CHEMBL4515289
7.46	EC50	35	nM	CHEMBL4577479
7.46	EC50	35	nM	CHEMBL4466792
7.46	EC50	35	nM	CHEMBL4567145
7.43	EC50	37	nM	CHEMBL4461964
7.43	EC50	37	nM	CHEMBL4440456
7.43	EC50	37	nM	CHEMBL4448781
7.40	EC50	40	nM	CHEMBL4526869
7.39	EC50	41	nM	CHEMBL4436647
7.37	EC50	43	nM	CHEMBL4440507
7.35	EC50	45	nM	CHEMBL4435430
7.34	EC50	46	nM	CHEMBL4453731
7.32	EC50	48	nM	CHEMBL4567290
7.30	EC50	50	nM	CHEMBL4454322

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
Hydrogen Peroxide	decreases expression, affects cotreatment, decreases activity, increases oxidation	2
Tobacco Smoke Pollution	decreases activity, decreases expression	2
Valproic Acid	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
1,2-oleoylphosphatidylcholine	affects binding	1
4-hydroxy-2-nonenal	decreases expression	1
polyserine	decreases reaction, increases chemical synthesis, increases metabolic processing	1
27-hydroxycholesterol	increases metabolic processing	1
K 7174	decreases expression	1
obeticholic acid	decreases expression	1
abrine	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Chlorine	affects binding, decreases activity, increases reaction	1
Cholesterol	increases acylation	1
Cholesterol Esters	decreases reaction, increases chemical synthesis, increases metabolic processing	1
Cisplatin	affects expression	1
Copper	decreases activity	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015040	Binding	Inhibition of LCAT activity in human plasma assessed as change in cholesteryl ester/free cholesterol ratio by cell based assay	Design, synthesis, and biological evaluation of (2R,alphaS)-3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol as potent and orally active cholesteryl ester transfer protein inhibitor. — *J Med Chem*

Clinical trials (associated diseases)

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

32 trials:

NCT	Phase	Status	Title
NCT01942291	Phase 4	COMPLETED	Short-term Effect of Extended-release Niacin on Endothelial Function.
NCT03368066	Phase 3	COMPLETED	Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?
NCT02697136	Phase 3	TERMINATED	CER-001 Therapy as a Novel Approach to Treat Genetic Orphan Diseases
NCT01283867	Phase 1	COMPLETED	Bioequivalence Study of Mycophenolate Mofetil 500 mg Tablets of Dr.Reddy’s Laboratories Limited Under Non-Fasting Conditions
NCT01283932	Phase 1	COMPLETED	Bioequivalence Study of Pantoprazole Sodium DR Tablets 40 mg of Dr. Reddy’s Laboratories Limited Under Fed Condition
NCT01314352	Phase 1	COMPLETED	Bioavailability Study of Desloratadine 5 mg Tablet of Dr. Reddy’s Under Fed Conditions
NCT01372306	Phase 1	COMPLETED	Galantamine Bioequivalence Study of Dr. Reddy’s Under Fed Condition
NCT01372358	Phase 1	COMPLETED	Bioavailability Study of Ciprofloxacin 1000 mg ER Tablets of Dr. Reddy’s Under Non-Fasting Conditions
NCT01503424	Phase 1	COMPLETED	Bioequivalence Study of Olanzapine Tablets, 5 mg Under Fed Study
NCT01503450	Phase 1	COMPLETED	Bioequivalence Study of Olanzapine Orally Disintegrating Tablets, 5 mg Under Fed Condition
NCT01505998	Phase 1	COMPLETED	Bioequivalence Study of Amlodipine Besylate/Benazepril HCl 10 mg/40 mg Capsules of Dr. Reddy’s Under Fed Conditions
NCT01567501	Phase 1	COMPLETED	Bioequivalence Study of Levocetirizine Dihydrochloride Tablets 5 mg Under Fed Condition
NCT01578265	Phase 1	COMPLETED	Bioequivalence Study of Ondansetron Tablets USP 8 mg Under Fed Condition
NCT01603186	Phase 1	COMPLETED	Bioequivalence Study of Quetiapine Fumarate Tablets 25 mg Under Fed Condition
NCT01618760	Phase 1	COMPLETED	Bioequivalence Study of Risperidone Tablet 1 mg Under Fed Condition
NCT01618825	Phase 1	COMPLETED	Bioequivalence Study of Lamotrigine Tablets 25 mg (2 x 25 mg Tablets) Under Fed Condition
NCT01722110	Phase 1	COMPLETED	Bioequivalence Study of Indomethacin Extended-Release Capsules 75 mg Under Fed Condition
NCT01735344	Phase 1	COMPLETED	Bioequivalence Study of Lisinopril Tablets 40 mg Under Fed Condition
NCT01735383	Phase 1	COMPLETED	Bioequivalence Study of Etodolac Tablet USP 500 mg Under Fed Condition
NCT01744873	Phase 1	COMPLETED	Bioequivalence Study of Bisoprolol Fumarate Tablet 10 mg Under Fed Condition
NCT01827878	Phase 1	COMPLETED	Bioequivalence Study of Lisinopril and Hydrochlorothiazide Tablets (20+25) mg Under Fed Conditions
NCT01884909	Phase 1	COMPLETED	Bioequivalence Study of Metoprolol Succinate Extended Release Tablets 200 mg Under Fed Conditions
NCT07396844	Phase 1	COMPLETED	The Food Effect on Pharmacokinetics of Fixed Dose Combination of Gemigliptin/Dapagliflozin/Metformin in Healthy Volunteers
NCT01782027	Not specified	TERMINATED	Mendelian Reverse Cholesterol Transport Study
NCT04737720	Not specified	COMPLETED	Intravenous ACP-501 for Familial LCAT Deficiency (rhLCAT)
NCT06217588	Not specified	RECRUITING	LCAT (Lecithin Cholesterol Acyl Transferase) Natural History Study
NCT05995119	Early Phase 1	COMPLETED	Comparative Bioavailability Study of TAH3311 5 mg Oral Dissolving Film vs ELIQUIS® 5 mg Tablet in Healthy Volunteers
NCT01721187	Not specified	COMPLETED	Satiety Effects on the Neural Valuation of Food
NCT03390881	Not specified	COMPLETED	Use of Breath Acetone aa a Marker of Energy Balance
NCT05837572	Not specified	UNKNOWN	Development of the Leeds Food Preference Questionnaire in Spanish
NCT00458055	Not specified	COMPLETED	High-Density Lipoprotein (HDL) Treatment Study
NCT01342666	Not specified	COMPLETED	Tomato Consumption and High Density Lipoprotein-cholesterol

Predicted chemistry — Sugi Predict

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