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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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GPIHBP1
glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1
Chromosome 8 Β· 8q24.3
NCBI Gene: 338328Ensembl: ENSG00000277494.3HGNC: HGNC:24945UniProt: Q8IV16
67PubMed Papers
21Diseases
0Drugs
23Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
chylomicron bindingprotein bindingpositive regulation of fatty acid biosynthetic processprotein stabilizationHyperlipoproteinemia type 1familial chylomicronemia syndromeAbnormality of the cardiovascular systemfamilial lipoprotein lipase deficiency
✦AI Summary

GPIHBP1 is a GPI-anchored endothelial protein essential for triglyceride metabolism that mediates lipoprotein lipase (LPL) transport from the basolateral to apical surface of capillary endothelial cells, thereby anchoring LPL in the capillary lumen where it processes triglyceride-rich lipoproteins 1. GPIHBP1 stabilizes LPL structure and activity, protecting it against ANGPTL4-mediated unfolding 2. The protein also binds chylomicrons and HDL particles, playing a critical role in lipolytic processing and lipid homeostasis 1. Loss-of-function GPIHBP1 mutations cause familial chylomicronemia syndrome with severe hypertriglyceridemia and acute pancreatitis risk 34. Notably, GPIHBP1 autoantibodies represent an acquired form of chylomicronemia by blocking LPL binding and transport, resulting in low plasma LPL levels and elevated triglycerides 5. Recent evidence demonstrates that liver-targeted LPL expression can therapeutically reduce hypertriglyceridemia and pancreatitis severity in GPIHBP1-deficient models, suggesting novel treatment approaches 6. GPIHBP1 expression is enriched in acinar-specific pancreatic endothelial cells, indicating tissue-specific metabolic functions 7.

Sources cited
1
GPIHBP1 shuttles LPL to capillary lumen, stabilizes LPL catalytic activity, and is essential for lipolytic processing of triglyceride-rich lipoproteins
PMID: 27185325
2
GPIHBP1 is LPL's essential partner in plasma triglyceride metabolism, preserving LPL structure and activity
PMID: 31269429
3
GPIHBP1 genetic variants cause monogenic familial chylomicronemia syndrome with severe hypertriglyceridemia
PMID: 38397180
4
Homozygous or biallelic GPIHBP1 loss-of-function variants cause familial chylomicronemia syndrome with severely elevated triglycerides
PMID: 32793115
5
GPIHBP1 autoantibodies prevent LPL binding and transport, causing acquired chylomicronemia with low plasma LPL levels
PMID: 32948662
6
Liver-targeted LPL expression decreases plasma triglycerides and reduces hypertriglyceridemia-associated acute pancreatitis in GPIHBP1-deficient models
PMID: 37974401
7
GPIHBP1 is expressed in acinar-specific pancreatic endothelial cells with metabolic regulatory functions
PMID: 39915484
Disease Associationsβ“˜21
Hyperlipoproteinemia type 1Open Targets
0.80Strong
familial chylomicronemia syndromeOpen Targets
0.69Moderate
Abnormality of the cardiovascular systemOpen Targets
0.41Moderate
familial lipoprotein lipase deficiencyOpen Targets
0.35Weak
pernicious anemiaOpen Targets
0.27Weak
alcohol drinkingOpen Targets
0.26Weak
physical activityOpen Targets
0.22Weak
preeclampsiaOpen Targets
0.20Weak
neoplasmOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
familial hypercholesterolemiaOpen Targets
0.07Suggestive
hypertriglyceridemia 2Open Targets
0.07Suggestive
breast carcinomaOpen Targets
0.06Suggestive
hyperlipidemia due to hepatic triglyceride lipase deficiencyOpen Targets
0.06Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.06Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.06Suggestive
Combined hyperlipidemiaOpen Targets
0.05Suggestive
sitosterolemia 2Open Targets
0.05Suggestive
Hyperlipoproteinemia 1DUniProt
Pathogenic Variants23
NM_178172.6(GPIHBP1):c.267C>A (p.Cys89Ter)Pathogenic
not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 89
NM_178172.6(GPIHBP1):c.52+2T>CPathogenic
Hyperlipoproteinemia, type 1D|not provided
β˜…β˜…β˜†β˜†2025
NM_178172.6(GPIHBP1):c.193T>C (p.Cys65Arg)Pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜…β˜†β˜†2024β†’ Residue 65
NM_178172.6(GPIHBP1):c.323C>G (p.Thr108Arg)Pathogenic
Hyperlipoproteinemia, type 1D|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 108
NM_178172.6(GPIHBP1):c.182-1G>TPathogenic
Hyperlipoproteinemia, type 1D|not provided
β˜…β˜…β˜†β˜†2023
NM_178172.6(GPIHBP1):c.422G>A (p.Trp141Ter)Likely pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜…β˜†β˜†2022β†’ Residue 141
NM_178172.6(GPIHBP1):c.320C>G (p.Ser107Cys)Likely pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜…β˜†β˜†β†’ Residue 107
NM_178172.6(GPIHBP1):c.299C>G (p.Ser100Ter)Likely pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜†β˜†β˜†2024β†’ Residue 100
NM_178172.6(GPIHBP1):c.182-2A>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_178172.6(GPIHBP1):c.381del (p.Thr127_Met128insTer)Likely pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜†β˜†β˜†2024β†’ Residue 127
NM_178172.6(GPIHBP1):c.158_161del (p.Arg53fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 53
NM_178172.6(GPIHBP1):c.70C>T (p.Gln24Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 24
NM_178172.6(GPIHBP1):c.203G>A (p.Cys68Tyr)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 68
NM_178172.6(GPIHBP1):c.397del (p.Ser133fs)Likely pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜†β˜†β˜†2020β†’ Residue 133
NM_178172.6(GPIHBP1):c.417_433del (p.Pro140fs)Pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜†β˜†β˜†2014β†’ Residue 140
NM_178172.6(GPIHBP1):c.331A>C (p.Thr111Pro)Pathogenic
Hyperlipoproteinemia, type 1D
β˜…β˜†β˜†β˜†2014β†’ Residue 111
NM_178172.6(GPIHBP1):c.194G>A (p.Cys65Tyr)Pathogenic
Hyperlipoproteinemia, type 1D|Hyperlipoproteinemia, type I
β˜…β˜†β˜†β˜†β†’ Residue 65
NM_178172.6(GPIHBP1):c.230G>A (p.Cys77Tyr)Likely pathogenic
Hyperlipoproteinemia, type 1D
β˜†β˜†β˜†β˜†2020β†’ Residue 77
NM_178172.6(GPIHBP1):c.344A>C (p.Gln115Pro)Pathogenic
Hyperlipoproteinemia, type 1D
β˜†β˜†β˜†β˜†2012β†’ Residue 115
NM_178172.6(GPIHBP1):c.266G>T (p.Cys89Phe)Pathogenic
Hyperlipoproteinemia, type 1D
β˜†β˜†β˜†β˜†2011β†’ Residue 89
View on ClinVar β†—
Related Genes
APOEProtein interaction100%APOBProtein interaction100%ANGPTL4Protein interaction93%ANGPTL8Protein interaction93%APOC3Protein interaction81%LPLProtein interaction81%
Tissue Expression6 tissues
Heart
100%
Brain
92%
Lung
90%
Ovary
33%
Liver
9%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
GPIHBP1APOEAPOBANGPTL4ANGPTL8APOC3LPL
PROTEIN STRUCTURE
Preparing viewer…
PDB6OAU Β· 2.48 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.72LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.08 [0.68–1.72]
RankingsWhere GPIHBP1 stands among ~20K protein-coding genes
  • #6,986of 20,598
    Most Researched67
  • #2,058of 5,498
    Most Pathogenic Variants23
  • #16,212of 17,882
    Most Constrained (LOEUF)1.72
Genes detectedGPIHBP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Understanding Hypertriglyceridemia: Integrating Genetic Insights.
PMID: 38397180
Genes (Basel) Β· 2024
1.00
2
AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats.
PMID: 37974401
Mol Ther Β· 2024
0.90
3
Chylomicronemia from GPIHBP1 autoantibodies.
PMID: 32948662
J Lipid Res Β· 2020
0.80
4
Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.
PMID: 39915484
Nat Commun Β· 2025
0.70
5
Genetics of Hypertriglyceridemia.
PMID: 32793115
Front Endocrinol (Lausanne) Β· 2020
0.60