NPC1

Chr 18q11.2

NPC intracellular cholesterol transporter 1

Aliases:: SLC65A1
MANE:: ENST00000269228.10

OMIM: 607623 ↗NCBI: 4864 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

NPC1 · O15118

v62025-08-01

Predicted Aligned Error matrix for NPC1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

85.1/ 100

Confident

1,278 residues

Confidence breakdown

Very high(≥ 90)45%
Confident(70–90)45%
Low(50–70)6%
Very low(< 50)4%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult onset neurodegenerative disorder
BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
BIALLELIC, autosomal or pseudoautosomal
Cholestasis
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops
BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia
BIALLELIC, autosomal or pseudoautosomal

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Disease associations (Open Targets)

Niemann-Pick disease, type C1
0.80
Niemann-Pick disease type C
0.78
Niemann-Pick disease
0.61
hereditary disease
0.54
hypertensive disorder
0.46
Abnormality of the skeletal system
0.44
obesity disorder
0.44
cerebellar ataxia
0.43
Cognitive impairment
0.43
heart failure
0.43

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

NPC intracellular cholesterol transporter 1

Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:12554680, PubMed:18772377, PubMed:27238017, PubMed:9211849, PubMed:9927649). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (PubMed:18772377, PubMed:19563754, PubMed:27238017, PubMed:27378690, PubMed:28784760, PubMed:9211849, PubMed:9927649). Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (PubMed:19563754). Mediates cholesterol transfer from lysosomes to endoplasmic reticulum by tethering endosomal/lysosomal compartments and endoplasmic reticulum membrane contact sites where it interacts with sterol transport protein GRAMD1B (PubMed:31537798). Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals (Probable). Inhibits cholesterol-mediated mTORC1 activation throught its interaction with SLC38A9 (PubMed:28336668)