NPC1
Chr 18ARNPC intracellular cholesterol transporter 1
Also known as: NPC, POGZ, SLC65A1
This protein mediates intracellular cholesterol trafficking by transporting low-density lipoproteins to late endosomal/lysosomal compartments where cholesterol is released, residing in the limiting membrane of endosomes and lysosomes with 13 transmembrane domains. Mutations cause Niemann-Pick disease types C1 and D, autosomal recessive neurodegenerative disorders characterized by accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments. The disease results from loss of protein function leading to defective cholesterol trafficking.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
399 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 21 | 3 | 10 | 0 | 34 |
Likely Pathogenic | 38 | 24 | 3 | 0 | 65 |
VUS | 2 | 119 | 11 | 12 | 144 |
Likely Benign | 0 | 0 | 53 | 57 | 110 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 61 | 146 | 78 | 69 | 354 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NPC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools