GPIHBP1

protein-coding

glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1, the group of LY6/PLAUR domain containing

Gene summary

This gene encodes a capillary endothelial cell protein that facilitates the lipolytic processing of triglyceride-rich lipoproteins. The encoded protein is a glycosylphosphatidylinositol-anchored protein that is a member of the lymphocyte antigen 6 (Ly6) family. This protein plays a major role in transporting lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lumen. Mutations in this gene are the cause of hyperlipoproteinemia, type 1D. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

MANE transcript

NM_178172.6

Inheritance

ClinVar variants

P:24U:77B:72

Top phenotype

Hyperlipoproteinemia, type ID

Max pathogenic AF

—

Genomic locus

chr8:143,213,218-143,217,170

External References & Databases

Ensembl (ENSG00000277494)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hyperlipoproteinemia, type 1DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014412

Submitter: PanelApp Australia

hyperlipoproteinemia, type 1DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014412

Submitter: Genomics England PanelApp

hyperlipoproteinemia, type 1DSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014412

Submitter: Orphanet

hyperlipoproteinemia, type 1DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014412

Submitter: Labcorp Genetics (formerly Invitae)

hyperlipoproteinemia, type 1DMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014412

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hyperlipoproteinemia, type IDAR

Manifestation: Cardiovascular; Gastrointestinal

Intervention: Cardiovascular; Gastrointestinal

Rationale: Individuals have been described with severe chylomicronemia/hypertriglyceridemia, and dietary measures (eg, low fat diet) have been described as beneficial related to sequelae such as pancreatitis and colitis, as well as other cardiovascular manifestations

Refs: 17883852; 19304573; 20026666; 20124439; 21816778; 22239554; 24614124; 24847059

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPIHBP1 variants in ClinVar

7 Conditions Cataloged

Cardiovascular phenotypeTotal: 125

not providedTotal: 88

Hyperlipoproteinemia, type 1DTotal: 25

GPIHBP1-related disorderTotal: 17

not specifiedTotal: 11

Hyperlipoproteinemia, type ITotal: 1

GPIHBP1-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178172.6. 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			2 clinvar	51 clinvar		53
missense	7 clinvar	4 clinvar	74 clinvar	20 clinvar	1 clinvar	106
nonsense	2 clinvar	3 clinvar	1 clinvar			6
start loss						0
frameshift	2 clinvar	3 clinvar				5
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar				3
Total	12	12	77	71	1	173

Highest pathogenic variant AF is 0.000008681707

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178172.6	RefSeq	NP_835466.2	4	MANE Select
ENST00000622500.2	Ensembl	ENSP00000480053.1	4	MANE Select
NM_001301772.2	RefSeq	NP_001288701.1	5	Standard
ENST00000852007.1	Ensembl	ENSP00000522066.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Metabolism of fat-soluble vitamins
Chylomicron remodeling
Post-translational modification: synthesis of GPI-anchored proteins

Biological Process

intracellular protein transport
protein import
protein localization to cell surface
cholesterol homeostasis
transcytosis

Molecular Function

lipid binding
protein transmembrane transporter activity
lipase binding
chylomicron binding
lipoprotein particle binding

Cellular Component

extracellular region
plasma membrane
external side of plasma membrane
membrane
basolateral plasma membrane

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a key role in the lipolytic processing of chylomicrons. Required for the transport of lipoprotein lipase LPL into the capillary lumen (By similarity). {ECO:0000250}.;
Disease: DISEASE: Hyperlipoproteinemia 1D (HLPP1D) [MIM:615947]: An autosomal recessive disorder characterized by hyperlipoproteinemia, decreased plasma LPL levels in some patients, high plasma triglyceride levels, and refractory fasting chylomicronemia. {ECO:0000269|PubMed:19304573, ECO:0000269|PubMed:20026666, ECO:0000269|PubMed:21314738, ECO:0000269|PubMed:21816778, ECO:0000269|PubMed:22239554, ECO:0000269|PubMed:23831619, ECO:0000269|PubMed:25387803, ECO:0000269|PubMed:27578123}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0855

Intolerance Scores

LoFtool: 0.387
RVIS EVS: 0.28
RVIS percentile EVS: 71.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.306

Gene Damage Prediction

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