GPIHBP1

Chr 8AR

glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1

Also known as: GPI-HBP1, HYPL1D

The encoded glycosylphosphatidylinositol-anchored protein transports lipoprotein lipase from the subendothelial spaces to the capillary lumen and anchors it on endothelial cell surfaces, facilitating triglyceride metabolism and lipid homeostasis. Mutations cause hyperlipoproteinemia type 1D, characterized by severe hypertriglyceridemia that typically presents in infancy with failure to thrive, recurrent pancreatitis, and eruptive xanthomas. This condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Hyperlipoproteinemia, type 1DMIM #615947
AR
0
Active trials
36
Pubs (1 yr)
97
P/LP submissions
13%
P/LP missense
1.10
LOEUF
DN
Mechanism· predicted
Clinical SummaryGPIHBP1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
84 unique Pathogenic / Likely Pathogenic· 74 VUS of 264 total submissions
📖
GeneReview available — GPIHBP1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.139
Z-score 1.44
OE 0.35 (0.141.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.04Z-score
OE missense 0.99 (0.851.16)
110 obs / 111.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.141.10)
00.351.4
Missense OE0.99 (0.851.16)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 2 / 5.7Missense obs/exp: 110 / 111.3Syn Z: 0.60
DN
0.6161th %ile
GOF
0.3689th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

264 submitted variants in ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic15
VUS74
Likely Benign79
Benign21
Conflicting5
69
Pathogenic
15
Likely Pathogenic
74
VUS
79
Likely Benign
21
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
7
59
0
69
Likely Pathogenic
4
4
7
0
15
VUS
0
60
13
1
74
Likely Benign
0
13
17
49
79
Benign
0
2
17
2
21
Conflicting
5
Total78611352263

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GPIHBP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Chylomicronemia from GPIHBP1 autoantibodies.
Miyashita K et al.·J Lipid Res
2020Review
Genetics of Hypertriglyceridemia.
Dron JS et al.·Front Endocrinol (Lausanne)
2020Review
[Familial chylomicronemia].
Quiroga-Padilla PJ et al.·Medicina (B Aires)
2020
Top 5 results · since 2015Search PubMed ↗