NPC2
Chr 14ARNPC intracellular cholesterol transporter 2
Also known as: EDDM1, HE1
The protein functions as an intracellular cholesterol transporter that works with NPC1 to facilitate cholesterol egress from the lysosomal compartment by transferring unesterified cholesterol from late endosomes/lysosomes to the cholesterol-binding domain of NPC1. Mutations cause Niemann-Pick disease type C2 through an autosomal recessive inheritance pattern, with disease resulting from loss of cholesterol transport function leading to lysosomal cholesterol accumulation.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
Cholesterol-binding protein in late endosomes/lysosomes. Biallelic LOF causes Niemann-Pick disease type C2. This is a classic autosomal recessive LOF gene; the DN prediction is incorrect.
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
200 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 | 9 | 2 | 5 | 0 | 16 |
Likely Pathogenic | 17 | 3 | 2 | 0 | 22 |
VUS | 2 | 28 | 10 | 0 | 40 |
Likely Benign | 0 | 7 | 45 | 46 | 98 |
Benign | 0 | 0 | 6 | 0 | 6 |
Conflicting | — | 9 | |||
| Total | 28 | 40 | 68 | 46 | 191 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NPC2 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools