Evidence for a Niemann-pick C (NPC) gene family: identification and characterization of NPC1L1

Genomics. 2000 Apr 15;65(2):137-45. doi: 10.1006/geno.2000.6151.


Niemann-Pick type C1 (NPC1) disease is caused by defects in the NPC1 protein, which result in perturbation of subcellular cholesterol transport. To identify related proteins that may be involved in subcellular cholesterol trafficking, the expressed sequence tag (EST) database was searched to find homologues of human NPC1. A short, weakly similar EST was identified and used to obtain a full-length human cDNA of about 5 kb and two alternatively spliced transcripts. The gene, named NPC1L1, was mapped to chromosome 7p13, contained 20 exons, including an unusually large 1526-bp exon 2, and spanned approximately 29 kb. In contrast to NPC1, the NPC1L1 putative promoter region contained a sterol-regulatory element. The predicted protein shared 42% identity and 51% similarity with NPC1. Interestingly, NPC1L1 contains the conserved amino-terminal "NPC1 domain" and the putative sterol-sensing domain, providing strong evidence that it is related to human NPC1 and suggesting that these may comprise a new family of NPC1-related proteins. However, the two differ with respect to their putative intracellular targeting signals. Collectively, these data suggest that NPC1L1 and NPC1 form part of a family of related proteins that may have similar functions at different subcellular locations, perhaps at sequential steps of the same cholesterol transport pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7
  • Conserved Sequence
  • DNA, Complementary
  • Evolution, Molecular
  • Exons
  • Expressed Sequence Tags
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Introns
  • Membrane Glycoproteins*
  • Membrane Proteins*
  • Membrane Transport Proteins
  • Molecular Sequence Data
  • Multigene Family*
  • Niemann-Pick C1 Protein
  • Niemann-Pick Diseases / genetics*
  • Promoter Regions, Genetic
  • Proteins / genetics*
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Sterols / metabolism
  • Tissue Distribution


  • Carrier Proteins
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • NPC1 protein, human
  • NPC1L1 protein, human
  • Niemann-Pick C1 Protein
  • Proteins
  • RNA, Messenger
  • Sterols

Associated data

  • GENBANK/AF192522
  • GENBANK/AF192523