Seroatlas · Human Serome Atlas

HCRT

Hypocretin neuropeptide precursor

Also known as: OREX_HUMAN, OX, PPOX

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

Protein identityUniProt · HPA

UniProt accession
O43612
Gene
HCRT
Ensembl
ENSG00000161610
Chromosome
17
Canonical length
131 aa
Protein class
Disease related genes, Human disease related genes, Predicted secreted proteins
Secretome location
Secreted to blood

OverviewNCBI Gene

This gene encodes a hypothalamic neuropeptide precursor protein that gives rise to two mature neuropeptides, orexin A and orexin B, by proteolytic processing. Orexin A and orexin B, which bind to orphan G-protein coupled receptors HCRTR1 and HCRTR2, function in the regulation of sleep and arousal. This neuropeptide arrangement may also play a role in feeding behavior, metabolism, and homeostasis. [provided by RefSeq, Jan 2010]

Canonical amino-acid sequenceUniProt

131 residues, UniProt reviewed canonical sequence.

>O43612|HCRT
     1  MNLPSTKVSW AAVTLLLLLL LLPPALLSSG AAAQPLPDCC RQKTCSCRLY ELLHGAGNHA
    61  AGILTLGKRR SGPPGLQGRL QRLLQASGNH AAGILTMGRR AGAEPAPRPC LGRRCSAPAA
   121  ASVAPGGQSG I

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HCRT 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
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.55
Highest tissue expression
401 nTPM

Expression across tissuesHPA

Tissue

  • hypothalamus: 401 nTPM
  • midbrain: 1.3 nTPM
  • basal ganglia: 0.5 nTPM
  • amygdala: 0.2 nTPM
  • cerebellum: 0.2 nTPM
  • cerebral cortex: 0.2 nTPM

Single-cell type

  • other brain neurons: 21 nCPM
  • neuroendocrine cells: 5.7 nCPM
  • foveolar cells: 4.7 nCPM
  • paneth cells: 3.9 nCPM
  • gastric progenitor cells: 3.8 nCPM
  • gastric chief cells: 2.2 nCPM

Immune cell

  • naive B-cell: 0.6 nTPM
  • basophil: 0.5 nTPM
  • MAIT T-cell: 0.5 nTPM
  • memory B-cell: 0.3 nTPM
  • memory CD8 T-cell: 0.3 nTPM
  • naive CD4 T-cell: 0.3 nTPM

Brain region

  • hypothalamus: 902 nTPM
  • thalamus: 110 nTPM
  • midbrain: 6.1 nTPM
  • basal ganglia: 3.5 nTPM
  • pons: 3.1 nTPM
  • cerebral cortex: 1.1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HCRT.

Disease | AllUniProt

Conditions HCRT is implicated in, by any mechanism.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 27 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Narcolepsy 1

Disease | ImmuneIEDB

Conditions an epitope on HCRT was assayed in.

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)
1.85
gnomAD pLI
0.03
gnomAD missense Z
0.76
DepMap mean gene effect
-0.14
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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

  • Prepro-orexin
  • Prepro-orexin

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

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

HCRT 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 HCRT as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HCRT. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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