GPIHBP1

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

Basic information

Region (hg38): 8:143213217-143217170

Links

ENSG00000277494 ∙ NCBI:338328 ∙ OMIM:612757 ∙ HGNC:24945 ∙ Uniprot:Q8IV16 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperlipoproteinemia, type 1D (Strong), mode of inheritance: AR
• hyperlipoproteinemia, type 1D (Moderate), mode of inheritance: AR
• hyperlipoproteinemia, type 1D (Strong), mode of inheritance: AR
• hyperlipoproteinemia, type 1D (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperlipoproteinemia, type ID	AR	Cardiovascular; Gastrointestinal	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	Cardiovascular; Gastrointestinal	17883852; 19304573; 20026666; 20124439; 21816778; 22239554; 24614124; 24847059

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPIHBP1 gene.

• Cardiovascular phenotype (60 variants)
• not provided (54 variants)
• Hyperlipoproteinemia, type 1D (14 variants)
• Inborn genetic diseases (5 variants)
• not specified (2 variants)
• GPIHBP1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPIHBP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				30	2	32
missense	2	2	36	4	2	46
nonsense	1	1				2
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			1	4	1	6
non coding			1	5	12	18
Total	5	4	37	39	16

Highest pathogenic variant AF is 0.0000328

Variants in GPIHBP1

This is a list of pathogenic ClinVar variants found in the GPIHBP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-143213275-C-T			Uncertain significance (Jun 24, 2022)
8-143213276-G-A		Cardiovascular phenotype • GPIHBP1-related disorder	Likely benign (Oct 25, 2021)
8-143213279-C-T		Cardiovascular phenotype	Benign (Jan 31, 2024)
8-143213280-G-A		Cardiovascular phenotype	Likely benign (Aug 03, 2021)
8-143213280-G-T		Cardiovascular phenotype	Uncertain significance (May 07, 2023)
8-143213288-C-T		Cardiovascular phenotype	Likely benign (Oct 07, 2020)
8-143213291-G-A		Cardiovascular phenotype	Likely benign (Apr 12, 2021)
8-143213297-C-T		Cardiovascular phenotype	Benign/Likely benign (Jan 06, 2024)
8-143213298-C-T		Cardiovascular phenotype	Uncertain significance (Feb 18, 2022)
8-143213308-T-G			Benign (Feb 01, 2024)
8-143213308-T-T		Cardiovascular phenotype	Benign (Jan 31, 2024)
8-143213309-C-T		Cardiovascular phenotype	Likely benign (Feb 14, 2020)
8-143213310-G-A		Cardiovascular phenotype	Uncertain significance (Jun 02, 2022)
8-143213313-C-T		Cardiovascular phenotype	Uncertain significance (Mar 07, 2022)
8-143213315-G-T		Cardiovascular phenotype	Likely benign (Oct 19, 2023)
8-143213323-C-A			Uncertain significance (Mar 16, 2023)
8-143213326-G-A			Uncertain significance (Jul 23, 2022)
8-143213333-G-A			Likely benign (Dec 14, 2023)
8-143213446-G-G			Benign (Aug 30, 2018)
8-143213459-G-A			Benign (Sep 21, 2018)
8-143213588-CGGCTGCAGGACAGTGAGTAGGGTGAGTAGGGTAGTAGGACAGTGAGTAGGGTGAGTA-C			Benign (Aug 30, 2018)
8-143213623-TAGGACAGTGAGTAGGGTGAGTAGGCTGC-T			Benign (Nov 18, 2018)
8-143213844-G-A		Cardiovascular phenotype	Likely benign (Nov 19, 2020)
8-143213859-C-G			Uncertain significance (Dec 01, 2021)
8-143213859-C-T		Cardiovascular phenotype	Likely benign (Oct 20, 2023)

GnomAD

Source: gnomAD

dbNSFP

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.
• Pathway: Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Chylomicron remodeling;Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;Metabolism;Transport of small molecules;Metabolism of vitamins and cofactors;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Retinoid metabolism and transport;G alpha (i) signalling events;Plasma lipoprotein remodeling;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.0855

Intolerance Scores

• loftool: 0.387
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.27

Haploinsufficiency Scores

• pHI: 0.0978
• hipred: N
• hipred_score: 0.146

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.306

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gpihbp1
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: intracellular protein transport;protein import;protein localization to cell surface;cholesterol homeostasis;transcytosis;protein stabilization;regulation of lipoprotein lipase activity;positive regulation of lipoprotein lipase activity;triglyceride homeostasis;response to heparin;protein transmembrane transport;positive regulation of chylomicron remnant clearance
• Cellular component: extracellular region;plasma membrane;external side of plasma membrane;membrane;basolateral plasma membrane;apical plasma membrane;anchored component of membrane;anchored component of external side of plasma membrane;high-density lipoprotein particle
• Molecular function: lipid binding;protein transmembrane transporter activity;lipase binding;chylomicron binding;lipoprotein particle binding