NPC2

Chr 14AR

NPC intracellular cholesterol transporter 2

Also known as: EDDM1, HE1

NCBI Gene: 10577 ENSG00000119655 UniProt: P61916 OMIM: 607625

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein containing a lipid recognition domain. The encoded protein may function in regulating the transport of cholesterol through the late endosomal/lysosomal system. Mutations in this gene have been associated with Niemann-Pick disease, type C2 and frontal lobe atrophy. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Niemann-pick disease, type C2MIM #607625

Clinical highlights

Gene-disease validity (ClinGen)

Niemann-Pick disease, type C2 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the established mechanism, though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

100

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

LOF

Mechanism· annotated