PLTP

protein-coding

phospholipid transfer protein, the group of BPI fold containing

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006227.4

Inheritance

—

ClinVar variants

U:135B:47

Top phenotype

PLTP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr20:45,898,621-45,912,155

External References & Databases

Ensembl (ENSG00000100979)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLTP variants in ClinVar

3 Conditions Cataloged

not providedTotal: 160

not specifiedTotal: 72

PLTP-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006227.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				35 clinvar	6 clinvar	41
missense			124 clinvar	4 clinvar	2 clinvar	130
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	135	39	8	182

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006227.4	RefSeq	NP_006218.1	15	MANE Select
ENST00000372431.8	Ensembl	ENSP00000361508.3	15	MANE Select
NM_001242920.2	RefSeq	NP_001229849.1	13	Standard
NM_001242921.1	RefSeq	NP_001229850.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cholesterol metabolism - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
Statin Pathway, Pharmacodynamics
PPAR Alpha Pathway
Nuclear Receptors Meta-Pathway

Biological Process

lipid metabolic process
lipid transport
vitamin E biosynthetic process
positive regulation of cholesterol efflux
phospholipid transport

Molecular Function

lipid transporter activity
phospholipid transporter activity
phosphatidylethanolamine binding
phosphatidylcholine transporter activity
diacylglycerol binding

Cellular Component

extracellular region
extracellular space
high-density lipoprotein particle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000477313
Coding exons: 15
Length: 13396
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0155	291	290	1.00	0.0000190	3170
Missense (PolyPhen)		99	109.14	0.90713		1311
Synonymous	-0.499	126	119	1.06	0.00000728	1043
Loss of Function	1.41	16	23.4	0.685	0.00000111	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00036	0.00036	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Facilitates the transfer of a spectrum of different lipid molecules, including diacylglycerol, phosphatidic acid, sphingomyelin, phosphatidylcholine, phosphatidylglycerol, cerebroside and phosphatidyl ethanolamine. Essential for the transfer of excess surface lipids from triglyceride-rich lipoproteins to HDL, thereby facilitating the formation of smaller lipoprotein remnants, contributing to the formation of LDL, and assisting in the maturation of HDL particles. PLTP 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 PC from phospholipid vesicles to high-density lipoproteins (HDL), and an inactive form that lacks this capability.;

Recessive Scores

pRec: 0.216

Intolerance Scores

LoFtool: 0.955
RVIS EVS: -0.44
RVIS percentile EVS: 24.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.717

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium