GPIHBP1

Chr 8AR

glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1

NCBI Gene: 338328 ENSG00000277494 UniProt: Q8IV16 OMIM: 612757

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Mediates the transport of lipoprotein lipase LPL from the basolateral to the apical surface of endothelial cells in capillaries (By similarity). Anchors LPL on the surface of endothelial cells in the lumen of blood capillaries (By similarity). Protects LPL against loss of activity, and against ANGPTL4-mediated unfolding (PubMed:27929370, PubMed:29899144). Thereby, plays an important role in lipolytic processing of chylomicrons by LPL, triglyceride metabolism and lipid homeostasis (PubMed:19304573, PubMed:21314738). Binds chylomicrons and phospholipid particles that contain APOA5 (PubMed:17997385, PubMed:19304573). Binds high-density lipoprotein (HDL) and plays a role in the uptake of lipids from HDL (By similarity)

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.101 OMIM phenotype

Clinical Summary— GPIHBP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.139

Z-score 1.44

OE 0.35 (0.14–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.85–1.16)

110 obs / 111.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.14–1.10)

0≤0.351.4

Missense OE?0.99 (0.85–1.16)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 2 / 5.7Missense obs/exp: 110 / 111.3Syn Z: 0.60

This gene — mechanism propensity

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.