PLTP

Summary

PLTP (phospholipid transfer protein, HGNC:9093) is a protein-coding gene on chromosome 20q13.12, encoding Phospholipid transfer protein (P55058). Mediates the transfer of phospholipids and free cholesterol from triglyceride-rich lipoproteins (low density lipoproteins or LDL and very low density lipoproteins or VLDL) into high-density lipoproteins (HDL) as well as the exchange of phospholipids between triglyceride-rich lip….

The protein encoded by this gene is one of at least two lipid transfer proteins found in human plasma. The encoded protein transfers phospholipids from triglyceride-rich lipoproteins to high density lipoprotein (HDL). In addition to regulating the size of HDL particles, this protein may be involved in cholesterol metabolism. At least two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5360 — RefSeq curated summary.

At a glance

• GWAS associations: 91
• Clinical variants (ClinVar): 234 total
• Druggable target: yes
• MANE Select transcript: NM_006227

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9093
Approved symbol	PLTP
Name	phospholipid transfer protein
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	BPIFE
Ensembl gene	ENSG00000100979
Ensembl biotype	protein_coding
OMIM	172425
Entrez	5360

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 24 protein_coding

ENST00000354050, ENST00000372420, ENST00000372431, ENST00000420868, ENST00000477313, ENST00000867284, ENST00000867285, ENST00000867286, ENST00000867287, ENST00000867288, ENST00000867289, ENST00000932731, ENST00000932732, ENST00000932733, ENST00000932734, ENST00000932735, ENST00000932736, ENST00000958184, ENST00000958185, ENST00000958186, ENST00000958187, ENST00000958188, ENST00000958189, ENST00000958190

RefSeq mRNA: 4 — MANE Select: NM_006227 NM_001242920, NM_001242921, NM_006227, NM_182676

CCDS: CCDS13386, CCDS13387, CCDS56196, CCDS56197

Canonical transcript exons

ENST00000372431 — 16 exons

Exon	Start	End
ENSE00000662442	45899462	45899538
ENSE00000662443	45899622	45899685
ENSE00000662444	45899836	45899878
ENSE00000662446	45904800	45904859
ENSE00000662447	45904942	45905118
ENSE00000662448	45906268	45906359
ENSE00000662449	45907692	45907755
ENSE00000662450	45907841	45907904
ENSE00000662451	45909516	45909671
ENSE00000662453	45911152	45911251
ENSE00000845074	45902267	45902334
ENSE00000845075	45902440	45902604
ENSE00000845076	45911353	45911463
ENSE00001432112	45912079	45912155
ENSE00003539934	45909942	45910070
ENSE00003843114	45898622	45899063

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.4563 / max 1982.3213, expressed in 1488 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187515	59.8544	1448
187509	0.5372	176
187514	0.3520	139
187511	0.2793	127
187510	0.1734	70
187513	0.1387	75
187512	0.1214	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	99.04	gold quality
right adrenal gland cortex	UBERON:0035827	98.81	gold quality
mucosa of stomach	UBERON:0001199	98.74	gold quality
right adrenal gland	UBERON:0001233	98.70	gold quality
gall bladder	UBERON:0002110	98.56	gold quality
right ovary	UBERON:0002118	98.41	gold quality
omental fat pad	UBERON:0010414	98.38	gold quality
peritoneum	UBERON:0002358	98.33	gold quality
endocervix	UBERON:0000458	98.31	gold quality
body of pancreas	UBERON:0001150	98.31	gold quality
left adrenal gland	UBERON:0001234	98.27	gold quality
coronary artery	UBERON:0001621	98.16	gold quality
left ovary	UBERON:0002119	98.16	gold quality
left coronary artery	UBERON:0001626	98.12	gold quality
left adrenal gland cortex	UBERON:0035825	98.06	gold quality
decidua	UBERON:0002450	97.95	gold quality
thymus	UBERON:0002370	97.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.90	gold quality
adrenal cortex	UBERON:0001235	97.83	gold quality
left uterine tube	UBERON:0001303	97.66	gold quality
adrenal gland	UBERON:0002369	97.61	gold quality
stromal cell of endometrium	CL:0002255	97.41	gold quality
ectocervix	UBERON:0012249	97.20	gold quality
thoracic aorta	UBERON:0001515	97.12	gold quality
ascending aorta	UBERON:0001496	97.05	gold quality
body of uterus	UBERON:0009853	97.03	gold quality
descending thoracic aorta	UBERON:0002345	96.85	gold quality
smooth muscle tissue	UBERON:0001135	96.81	gold quality
placenta	UBERON:0001987	96.63	gold quality
synovial joint	UBERON:0002217	96.62	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	4908.27
E-MTAB-6678	yes	4263.25
E-GEOD-84465	yes	3251.42
E-MTAB-6701	yes	2592.28
E-GEOD-124472	yes	1900.71
E-CURD-79	yes	1725.80
E-MTAB-6911	yes	521.53
E-MTAB-8142	yes	44.00
E-MTAB-10553	yes	42.94
E-HCAD-5	yes	32.89
E-MTAB-10287	yes	22.35
E-GEOD-81547	yes	21.99
E-HCAD-10	yes	20.60
E-GEOD-93593	yes	16.82
E-CURD-112	yes	16.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, GLI1, NR0B2, NR1H2, NR1H3, NR1H4, TCF3

miRNA regulators (miRDB)

18 targeting PLTP, 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-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-1322	97.98	68.96	625
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-1225-5P	96.76	66.85	417
HSA-MIR-184	94.24	64.40	152

Literature-anchored findings (GeneRIF, showing 40)

• Human PLTP expressed in plasma from transgenic mice contributes to the formation of pre beta-HDL, whereas the expression of human cholesterol ester transfer protein does not affect this process. (PMID:11716766)
• This protein and pre-beta-high density lipoprotein are degraded by mast cell chymase, the high affinity efflux of cholesterol from macrophage foam cells is impaired. (PMID:12531890)
• The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions. (PMID:12612088)
• Elevation of PLTP activity results in rapid disposal of cholesterol from the body via increased conversion into bile acids and subsequent excretion. (PMID:12649089)
• PLTP is expressed by macrophages, is regulated by cholesterol loading, and is present in atherosclerotic lesions (PMID:12730304)
• elevated PLTP activity in hypertriglyceridemia is related to insulin resistance and not to increased PLTP mass (PMID:12754275)
• HepG2-derived PLTP resembles in several aspects the high-activity form of PLTP found in human plasma (PMID:12810820)
• PLTP is present in human atherosclerotic lesions, and its distribution suggests roles for PLTP in both cellular cholesterol metabolism and lipoprotein retention on extracellular matrix (PMID:12835223)
• seminal PLTP concentrations represented 25% of the concentration measured in blood plasma; seminal PLTP activity was partially associated with prostasomes; higher PLTP activity was measured in seminal plasma samples with low seminal vesicle secretions (PMID:12837922)
• PLTP concentration serve as a predictor of Coronary disease, independent of HDL cholesterol, triglycerides and other established risk factors. (PMID:14695459)
• expression of PLTP results in increased atherosclerosis in spite of reduced apoB-containing lipoproteins, by reduction of HDL and of HDL-associated antioxidant enzyme activities (PMID:14993244)
• Phospholipid transfer protein is emerging as a multifaceted and multifunctional player in lipid and lipoprotein metabolism [review]. (PMID:15166780)
• patthophysiologic role of PLTP in decreasing the vitamin E content of apolipoprotein B-containing lipoproteins in Type 2 diabetes. (PMID:15448094)
• A major role for stimulated phospholipid transfer protein (PLTP) activity is identified in the recycling of pre-beta 1-high density lipoprotein during reverse cholesterol transport. (PMID:15544352)
• The findings of reduced PLTP activity in AD CSF, and the observation that PLTP can influence apoE secretion in astrocytes suggest a potential link between alterations in the brain lipid metabolism and AD pathogenesis. (PMID:15795933)
• ApoE proteoliposomes induced a concentration-dependent activation of low-activity form of PLTP. (PMID:15845396)
• Human tear fluid contains catalytically active phospholipid transfer protein (PLTP), which resembles the active form of PLTP present in plasma. (PMID:15924430)
• These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism. (PMID:16388083)
• The increase in PLTP activity in type 2 diabetes is partly related to the changes in apolipoprotein E. (PMID:16389649)
• Active plasma phospholipid transfer protein is associated with apoA-I- but not apoE-containing lipoproteins. (PMID:16520487)
• Association between the decrease in PLTP activity and aapolipoprotein E during statin treatment supports the hypothesis that apoE may prevent PLTP inactivation in diabetes. (PMID:16644710)
• results suggest that secretion-competent PLTP requires glycosylation but that no single glycosylation site is required (PMID:16862459)
• PLTP is capable of transferring lipids by a shuttle mechanism and formation of a ternary complex between PLTP, acceptor, and donor particles is not necessary for phospholipid transfer (PMID:17260960)
• Lipolysis of triglyceride-rich lipoproteins and their remodelling by PLTP interact to disturb cellular phospholipid flux and intracellular signaling processes, ultimately leading to apoptosis in human macrophages and endothelial cells. (PMID:17272752)
• We resequenced candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 1 in phospholipid transfer protein (PLTP), leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. (PMID:17303779)
• phospholipid and cholesteryl ester transfer proteins are important in very low and high-density lipoprotein metabolism and display concerted actions in patients with type 2 diabetes [review] (PMID:17495597)
• in non-diabetic, non-smoking subjects low rather than high PLTP activity is a marker for the presence of peripheral arterial disease (PMID:17553507)
• the potential interaction between human plasma phospholipid transfer protein (and apolipoprotein A-I (apoA-I), double transgenic animals (hPLTPtg/hApoAItg) were compared with hApoAItg mice. (PMID:17761633)
• PTLP activity is positively associated with serum ALT1, GOT1 and GOT2 in type 2 diabetes mellitus and metabolic syndrome. (PMID:17877759)
• Cholesterol efflux from macrophage foam cells is enhanced by active PLTP through generation of two types of acceptor particles. (PMID:17900150)
• Increased PLTP activity associated with the impaired cellular cholesterol efflux in type 2 diabetic subjects with coronary artery disease. (PMID:17917406)
• it is concluded that apoE enhances the capacity of PLTP to remodel HDL but reduces the ability of HDL to participate in PLTP-mediated phospholipid transfers. (PMID:17921435)
• ABCA1-dependent cholesterol efflux requires an amphipathic helical region of the N-terminal barrel of phospholipid transfer protein (PMID:18287097)
• Acute elevation of PLTP activity destabilizes atherosclerotic lesions and aggravates pre-existing atherosclerosis. (PMID:18421000)
• Association of rs2294213 with HDL-C levels into the extremes of the HDL distribution. (PMID:19013296)
• Elevation of systemic PLTP, but not macrophage-PLTP, impairs macrophage reverse cholesterol transport in transgenic mice. (PMID:19100548)
• The results confirm the atherogenic behavior of PLTP in coronary artery disease. (PMID:19135989)
• These findings indicate that plasma HDL level is an important regulator of plasma PLTP and might play a role in the stabilization of PLTP in plasma. (PMID:19422933)
• PLTP activity may represent a novel marker of left ventricular systolic dysfunction in patients with known or suspected coronary artery disease. (PMID:19446293)
• PLTP may be an important modulator of signal transduction pathways in human neurons. (PMID:19472218)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pltp	ENSDARG00000104495
mus_musculus	Pltp	ENSMUSG00000017754
rattus_norvegicus	Pltp	ENSRNOG00000016488
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

Phospholipid transfer protein — P55058 (reviewed: P55058)

Alternative names: Lipid transfer protein II

All UniProt accessions (1): P55058

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the transfer of phospholipids and free cholesterol from triglyceride-rich lipoproteins (low density lipoproteins or LDL and very low density lipoproteins or VLDL) into high-density lipoproteins (HDL) as well as the exchange of phospholipids between triglyceride-rich lipoproteins themselves. Facilitates the transfer of a spectrum of different lipid molecules, including diacylglycerol, phosphatidic acid, sphingomyelin, phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol, cerebroside and phosphatidyl ethanolamine. Plays an important role in HDL remodeling which involves modulating the size and composition of HDL. Also plays a key role in the uptake of cholesterol from peripheral cells and tissues that is subsequently transported to the liver for degradation and excretion. Two distinct forms of PLTP exist in plasma: an active form that can transfer phosphatidylcholine from phospholipid vesicles to HDL, and an inactive form that lacks this capability.

Subcellular location. Secreted. Nucleus.

Tissue specificity. Widely expressed. Highest level of expression in the ovary, thymus and placenta, with moderate levels found in the pancreas, small intestine, testis, lung and prostrate. Low level expression in the kidney, liver and spleen, with very low levels found in the heart, colon, skeletal muscle, leukocytes and brain. Expressed in the cortical neurons.

Post-translational modifications. Glycosylation is necessary for secretion and its phospholipid transfer activity.

Similarity. Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.

Isoforms (4)

UniProt ID	Names	Canonical?
P55058-1	1	yes
P55058-2	2
P55058-3	3
P55058-4	4

RefSeq proteins (4): NP_001229849, NP_001229850, NP_006218, NP_872617 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001124	Lipid-bd_serum_glycop_C	Domain
IPR017942	Lipid-bd_serum_glycop_N	Domain
IPR017943	Bactericidal_perm-incr_a/b_dom	Homologous_superfamily
IPR017954	Lipid-bd_serum_glycop_CS	Conserved_site
IPR030675	BPI/LBP	Family
IPR032942	BPI/LBP/Plunc	Family

Pfam: PF01273, PF02886

Catalyzed reactions (Rhea), 10 shown:

• a 1,2-diacyl-sn-glycero-3-phosphate(in) = a 1,2-diacyl-sn-glycero-3-phosphate(out) (RHEA:36435)
• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(in) = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(out) (RHEA:38691)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) (RHEA:38895)
• a 1,2-diacyl-sn-glycerol(in) = a 1,2-diacyl-sn-glycerol(out) (RHEA:39723)
• a sphingomyelin(in) = a sphingomyelin(out) (RHEA:39727)
• a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol)(in) = a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol)(out) (RHEA:39743)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(in) = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(out) (RHEA:46488)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine(in) = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine(out) (RHEA:46492)
• N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine(in) = N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine(out) (RHEA:46496)

UniProt features (33 total): mutagenesis site 11, sequence variant 7, glycosylation site 6, splice variant 3, sequence conflict 3, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55058-F1	89.36	0.71

Functional residue map

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

Disulfide bonds (1): 146–185

Glycosylation sites (6): 64, 94, 117, 143, 245, 398

Mutagenesis-validated functional residues (11):

Position	Phenotype
64	increased nuclear localization; when associated with a-94; a-117 and a-143.
66	significant reduction in phospholipid transfer activity. no effect on secretion.
94	increased nuclear localization; when associated with a-64; a-117 and a-143.
96	significant reduction in phospholipid transfer activity. increased secretion.
117	increased nuclear localization; when associated with a-64; a-94 and a-143.
119	significant reduction in phospholipid transfer activity. increased secretion.
143	increased nuclear localization; when associated with a-64; a-94 and a-117.
145	significant reduction in phospholipid transfer activity. reduced secretion.
176	significant reduction in hdl-binding and absence of lipid transfer activity.
247	significant reduction in phospholipid transfer activity. reduced secretion.
400	significant reduction in phospholipid transfer activity. reduced secretion.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8964058	HDL remodeling
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux

MSigDB gene sets: 288 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, WALLACE_PROSTATE_CANCER_RACE_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MODULE_151, SP3_Q3, GOBP_POSITIVE_REGULATION_OF_CHOLESTEROL_EFFLUX, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_CHOLESTEROL_EFFLUX, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP

GO Biological Process (11): lipid metabolic process (GO:0006629), lipid transport (GO:0006869), vitamin E biosynthetic process (GO:0010189), positive regulation of cholesterol efflux (GO:0010875), phospholipid transport (GO:0015914), flagellated sperm motility (GO:0030317), high-density lipoprotein particle remodeling (GO:0034375), ceramide transport (GO:0035627), glycolipid transport (GO:0046836), sterol transport (GO:0015918), intermembrane lipid transfer (GO:0120009)

GO Molecular Function (22): high-density lipoprotein particle binding (GO:0008035), phosphatidylethanolamine binding (GO:0008429), phosphatidylinositol transfer activity (GO:0008526), diacylglycerol binding (GO:0019992), low-density lipoprotein particle binding (GO:0030169), phosphatidylcholine binding (GO:0031210), very-low-density lipoprotein particle binding (GO:0034189), phosphatidic acid binding (GO:0070300), ceramide binding (GO:0097001), phospholipid transfer activity (GO:0120014), ceramide transfer activity (GO:0120017), phosphatidylcholine transfer activity (GO:0120019), cholesterol transfer activity (GO:0120020), diacylglyceride transfer activity (GO:0140337), sphingomyelin transfer activity (GO:0140338), phosphatidylglycerol transfer activity (GO:0140339), cerebroside transfer activity (GO:0140340), phosphatidylglycerol binding (GO:1901611), phosphatidylethanolamine transfer activity (GO:1904121), phosphatidic acid transfer activity (GO:1990050), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), high-density lipoprotein particle (GO:0034364)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Plasma lipoprotein remodeling	1
NR1H2 and NR1H3-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid transport	5
phospholipid binding	5
phospholipid transfer activity	5
lipoprotein particle binding	3
lipid transfer activity	3
anion binding	2
sphingolipid transfer activity	2
primary metabolic process	1
transport	1
lipid localization	1
vitamin E metabolic process	1
fat-soluble vitamin biosynthetic process	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
organophosphate ester transport	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
plasma lipoprotein particle remodeling	1
nitrogen compound transport	1
carbohydrate derivative transport	1
organic hydroxy compound transport	1
membrane organization	1
phosphatidylinositol binding	1
lipid binding	1
cation binding	1
quaternary ammonium group binding	1
protein binding	1
sphingolipid binding	1
phospholipid transport	1
ceramide binding	1
phosphatidylcholine binding	1
cholesterol binding	1
sterol transfer activity	1
glycolipid transfer activity	1
ceramide transfer activity	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
plasma lipoprotein particle	1

Protein interactions and networks

STRING

1302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLTP	APOB	P04114	877
PLTP	APOA1	P02647	859
PLTP	LIPC	P11150	853
PLTP	BPIFA1	Q9NP55	836
PLTP	LCAT	P04180	828
PLTP	ABCA1	O95477	826
PLTP	APOA2	P02652	825
PLTP	APOE	P02649	822
PLTP	ALG1	Q9BT22	762
PLTP	LPL	P06858	757
PLTP	ALG6	Q9Y672	749
PLTP	SCARB1	Q8WTV0	731
PLTP	APOF	Q13790	726
PLTP	NPC1L1	Q9UHC9	717
PLTP	CYP7A1	P22680	687

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
PLTP	SEL1L3	psi-mi:“MI:0914”(association)	0.530
PLTP	CREB3	psi-mi:“MI:0915”(physical association)	0.490
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
DHFR2	MANBA	psi-mi:“MI:0914”(association)	0.350
NMS	MANBA	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350
PLTP	CLGN	psi-mi:“MI:0914”(association)	0.350
SPINK14	ZZEF1	psi-mi:“MI:0914”(association)	0.350
LCN6	COCH	psi-mi:“MI:0914”(association)	0.350
HYOU1	SNX2	psi-mi:“MI:0914”(association)	0.350
TAFA5	NEBL	psi-mi:“MI:0914”(association)	0.350
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350
PLTP	CANX	psi-mi:“MI:0914”(association)	0.350
FGG	ACOT7	psi-mi:“MI:0914”(association)	0.350
GPRC5C	PLAU	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): PLTP (Affinity Capture-MS), PLTP (Affinity Capture-MS), PLTP (Affinity Capture-MS), CLGN (Affinity Capture-MS), CANX (Affinity Capture-MS), HLA-F (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), RDH11 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), EPB41L5 (Affinity Capture-MS), ADPGK (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), PGAP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A481NSZ4, A0JPN3, A2BGH0, A6QP57, D4A5U3, G3HIK4, O02668, O76879, P11597, P17213, P17453, P17454, P18428, P19823, P19827, P22687, P47896, P55058, P55065, P59826, P59827, P97278, Q05701, Q05704, Q08188, Q08189, Q0VCM5, Q10011, Q24764, Q28739, Q29052, Q2TBI0, Q61114, Q61702, Q61703, Q61805, Q63313, Q67E05, Q6AXU0, Q80ZU7

Diamond homologs: P55058, P55065, Q28739

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	134
Likely benign	69
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

2287 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45899457:CT:C	donor_loss	1.0000
20:45899458:TCA:T	donor_loss	1.0000
20:45899459:CACC:C	donor_loss	1.0000
20:45899460:A:T	donor_loss	1.0000
20:45899461:CCG:C	donor_gain	1.0000
20:45899534:CCGCT:C	acceptor_gain	1.0000
20:45899535:CGCT:C	acceptor_gain	1.0000
20:45899535:CGCTC:C	acceptor_gain	1.0000
20:45899536:GCTC:G	acceptor_loss	1.0000
20:45899537:CT:C	acceptor_gain	1.0000
20:45899538:TC:T	acceptor_loss	1.0000
20:45899539:C:A	acceptor_loss	1.0000
20:45899539:C:CC	acceptor_gain	1.0000
20:45899540:T:C	acceptor_loss	1.0000
20:45899618:TTACC:T	donor_loss	1.0000
20:45899619:TACCA:T	donor_loss	1.0000
20:45899620:A:AC	donor_gain	1.0000
20:45899621:C:CA	donor_loss	1.0000
20:45899621:C:CC	donor_gain	1.0000
20:45899681:ATCAG:A	acceptor_gain	1.0000
20:45899682:TCAG:T	acceptor_gain	1.0000
20:45899683:CAG:C	acceptor_gain	1.0000
20:45899683:CAGC:C	acceptor_gain	1.0000
20:45899684:AG:A	acceptor_gain	1.0000
20:45899686:C:CC	acceptor_gain	1.0000
20:45899696:C:CT	acceptor_gain	1.0000
20:45899697:G:T	acceptor_gain	1.0000
20:45899834:A:AC	donor_gain	1.0000
20:45899835:C:CC	donor_gain	1.0000
20:45902262:CCTA:C	donor_loss	1.0000

AlphaMissense

3188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45909565:A:G	C146R	0.991
20:45909564:C:G	C146S	0.990
20:45909565:A:T	C146S	0.990
20:45911379:C:G	R25P	0.990
20:45907751:C:G	C185S	0.989
20:45907752:A:G	C185R	0.989
20:45907752:A:T	C185S	0.989
20:45909564:C:T	C146Y	0.989
20:45907751:C:T	C185Y	0.988
20:45899058:G:C	F455L	0.986
20:45899058:G:T	F455L	0.986
20:45899060:A:G	F455L	0.986
20:45899514:A:G	I436T	0.985
20:45904987:G:C	S279R	0.984
20:45904987:G:T	S279R	0.984
20:45904989:T:G	S279R	0.984
20:45909563:G:C	C146W	0.984
20:45905018:G:A	S269F	0.982
20:45907750:G:C	C185W	0.982
20:45904997:G:T	A276D	0.980
20:45911376:A:T	V26D	0.979
20:45909643:C:G	A120P	0.978
20:45909969:A:G	F101S	0.976
20:45905035:C:A	M263I	0.975
20:45905035:C:G	M263I	0.975
20:45905035:C:T	M263I	0.975
20:45907851:A:G	L180P	0.975
20:45905110:G:C	F238L	0.974
20:45905110:G:T	F238L	0.974
20:45905112:A:G	F238L	0.974

dbSNP variants (sampled 300 via entrez): RS1000286743 (20:45908737 G>A,C), RS1000499849 (20:45913033 G>A), RS1001165990 (20:45898283 G>A), RS1001326045 (20:45898586 A>G), RS1001436574 (20:45904600 C>A,T), RS1001580285 (20:45909431 C>T), RS1001843592 (20:45907763 G>A,C), RS1001906298 (20:45909163 C>T), RS1002001120 (20:45901491 G>A), RS1002318787 (20:45908145 A>T), RS1002369960 (20:45913498 G>A,C), RS1002507900 (20:45910704 G>C,T), RS1002634226 (20:45903855 G>A), RS1002665148 (20:45904132 A>T), RS1003529416 (20:45900398 C>A,T)

Disease associations

OMIM: gene MIM:172425 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

91 associations (top):

Study	Trait	p-value
GCST000286_5	Triglycerides	7.000000e-11
GCST000290_9	HDL cholesterol	4.000000e-09
GCST000533_18	Lipid metabolism phenotypes	3.000000e-49
GCST000533_19	Lipid metabolism phenotypes	4.000000e-40
GCST000533_20	Lipid metabolism phenotypes	8.000000e-37
GCST000533_21	Lipid metabolism phenotypes	1.000000e-45
GCST000755_34	HDL cholesterol	2.000000e-22
GCST000758_16	Triglycerides	5.000000e-18
GCST001392_15	Lipid metabolism phenotypes	2.000000e-31
GCST001639_6	Metabolite levels	2.000000e-42
GCST001725_65	Inflammatory bowel disease	1.000000e-13
GCST002216_4	Triglycerides	2.000000e-34
GCST002223_70	HDL cholesterol	5.000000e-40
GCST002897_1	Triglycerides	9.000000e-21
GCST002899_30	HDL cholesterol	9.000000e-18
GCST003648_2	Pathological gambling	1.000000e-06
GCST003680_12	C-reactive protein levels or HDL-cholesterol levels (pleiotropy)	5.000000e-29
GCST003681_21	C-reactive protein levels or triglyceride levels (pleiotropy)	2.000000e-24
GCST003854_51	Gut microbiota (functional units)	4.000000e-06
GCST003854_54	Gut microbiota (functional units)	4.000000e-06
GCST004207_10	HDL cholesterol	3.000000e-08
GCST004232_34	HDL cholesterol levels	2.000000e-09
GCST004232_7	HDL cholesterol levels	6.000000e-39
GCST004234_15	HDL cholesterol levels	2.000000e-08
GCST004238_11	Triglyceride levels	6.000000e-10
GCST006003_26	Triglyceride levels	1.000000e-14
GCST006005_52	High density lipoprotein cholesterol levels	4.000000e-14
GCST006940_145	Neurociticism	1.000000e-10
GCST006944_15	Experiencing mood swings	1.000000e-09
GCST008070_112	HDL cholesterol levels	1.000000e-07

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004529	lipid measurement
EFO:0004723	coronary artery calcification
EFO:0004458	C-reactive protein measurement
EFO:0007874	gut microbiome measurement
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0004329	alcohol drinking
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5962 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 40 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.10	IC50	8000	nM	CHEMBL1222668
5.00	IC50	1e+04	nM	CHEMBL1222737

PubChem BioAssay actives

2 with measured affinity, of 23 total; 2 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
N-(4,5-diphenyl-1,3-selenazol-2-yl)-3,4-dihydroxybenzamide	501651: Inhibition of PLTP	ic50	8.0000	uM
N-[5-butyl-4-(4-hydroxyphenyl)-1,3-selenazol-2-yl]-3,4,5-trihydroxybenzamide	501651: Inhibition of PLTP	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	5
bisphenol A	decreases expression, increases expression, affects cotreatment	3
Aflatoxin B1	increases expression, affects expression	3
entinostat	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
periodate-oxidized adenosine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
JP8 aviation fuel	decreases expression	1
chloropicrin	increases expression	1
T0901317	increases expression	1
GW 501516	affects binding, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
candoxin	decreases expression	1
obeticholic acid	decreases expression	1
GW 3965	increases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015039	Binding	Inhibition of PLTP activity assessed as phosphatidylcholine transferred from [3H]phosphatidylcholine (dipalmitoyl)-labeled liposomes to HDL by cell based liquid scintillation counter	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)

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