Seroatlas · Human Serome Atlas

NPC1

NPC intracellular cholesterol transporter 1

Also known as: NPC1_HUMAN, SLC65A1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O15118
Gene: NPC1
Ensembl: ENSG00000141458
Chromosome: 18
Canonical length: 1278 aa
Protein class: Disease related genes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]

Canonical amino-acid sequenceUniProt

1278 residues, UniProt reviewed canonical sequence.

>O15118|NPC1
     1  MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP LPKDGYDLVQ
    61  ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC FYNLLNLFCE LTCSPRQSQF
   121  LNVTATEDYV DPVTNQTKTN VKELQYYVGQ SFANAMYNAC RDVEAPSSND KALGLLCGKD
   181  ADACNATNWI EYMFNKDNGQ APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC
   241  QDCSIVCGPK PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS
   301  EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP GCVIFFSLVF
   361  ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG PFFRTEQLII RAPLTDKHIY
   421  QPYPSGADVP FGPPLDIQIL HQVLDLQIAI ENITASYDNE TVTLQDICLA PLSPYNTNCT
   481  ILSVLNYFQN SHSVLDHKKG DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP
   541  VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT
   601  ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV DSKVSLGIAG
   661  ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD NIFILVQAYQ RDERLQGETL
   721  DQQLGRVLGE VAPSMFLSSF SETVAFFLGA LSVMPAVHTF SLFAGLAVFI DFLLQITCFV
   781  SLLGLDIKRQ EKNRLDIFCC VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA
   841  IFVGVLSFSI AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT
   901  SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV KPQSSCCRVD
   961  NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP MFLSDNPNPK CGKGGHAAYS
  1021  SAVNILLGHG TRVGATYFMT YHTVLQTSAD FIDALKKARL IASNVTETMG INGSAYRVFP
  1081  YSVFYVFYEQ YLTIIDDTIF NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG
  1141  VMWLWGISLN AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS
  1201  GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY IGPSVNKAKS
  1261  CATEERYKGT ERERLLNF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NPC1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Other membrane
Secreted: No
Transmembrane segments: 13
Mean surface accessibility (rSASA): 0.24
Highest tissue expression: 81 nTPM

Expression across tissuesHPA

Tissue

adrenal gland: 81 nTPM
parathyroid gland: 68 nTPM
spinal cord: 64 nTPM
bone marrow: 37 nTPM
salivary gland: 34 nTPM
hippocampal formation: 34 nTPM

Single-cell type

alveolar cells type 2: 534 nCPM
endometrial glandular cells: 508 nCPM
urothelial cells: 486 nCPM
epididymal basal cells: 434 nCPM
ocular epithelial cells: 328 nCPM
epididymal clear cells: 323 nCPM

Immune cell

plasmacytoid DC: 71 nTPM
gdT-cell: 30 nTPM
memory CD8 T-cell: 21 nTPM
MAIT T-cell: 21 nTPM
T-reg: 18 nTPM
naive CD8 T-cell: 15 nTPM

Brain region

white matter: 228 nTPM
medulla oblongata: 165 nTPM
basal ganglia: 155 nTPM
pons: 135 nTPM
cerebellum: 135 nTPM
midbrain: 133 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NPC1.

Disease | AllUniProt

Conditions NPC1 is implicated in, by any mechanism.

Niemann-Pick disease C1 (NPC1) MIM:257220

Disease | GeneticClinVar

639 pathogenic / likely-pathogenic of 2,784 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.49
gnomAD pLI: 0
gnomAD missense Z: 1.09
DepMap mean gene effect: -0.07
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NPC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NPC1 as an antibody target. Whether an autoantibody or antibody against NPC1 could matter depends on whether native NPC1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NPC1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label NPC1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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