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, metabolis... See more...

Aliases for HCRT Gene

Aliases for HCRT Gene

  • Hypocretin Neuropeptide Precursor 2 3 5
  • Orexin 2 3 4
  • Prepro-Orexin 2 3
  • PPOX 3 4
  • OX 3 4
  • Hypocretin (Orexin) Neuropeptide Precursor 2
  • Hypocretin (Orexin) Neuropeptide 3
  • Hypocretin 4
  • NRCLP1 3
  • PPORX 4
  • Hcrt 4

External Ids for HCRT Gene

Previous GeneCards Identifiers for HCRT Gene

  • GC17M039901
  • GC17M042492
  • GC17M040244
  • GC17M040709
  • GC17M037589
  • GC17M040337
  • GC17M036101

Summaries for HCRT Gene

Entrez Gene Summary for HCRT 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]

GeneCards Summary for HCRT Gene

HCRT (Hypocretin Neuropeptide Precursor) is a Protein Coding gene. Diseases associated with HCRT include Narcolepsy 1 and Narcolepsy. Among its related pathways are Peptide ligand-binding receptors and Neuroscience. Gene Ontology (GO) annotations related to this gene include type 1 hypocretin receptor binding and type 2 hypocretin receptor binding.

UniProtKB/Swiss-Prot Summary for HCRT Gene

  • Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity.

Additional gene information for HCRT Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HCRT Gene

Genomics for HCRT Gene

GeneHancer (GH) Regulatory Elements for HCRT Gene

Promoters and enhancers for HCRT Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HCRT on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HCRT gene promoter:
  • ARP-1
  • CREB
  • deltaCREB
  • FOXJ2
  • HOXA5
  • ITF-2
  • NRSF form 1
  • NRSF form 2
  • STAT3
  • Tal-1beta

Genomic Locations for HCRT Gene

Genomic Locations for HCRT Gene
chr17:42,184,060-42,185,452
(GRCh38/hg38)
Size:
1,393 bases
Orientation:
Minus strand
chr17:40,336,078-40,337,470
(GRCh37/hg19)
Size:
1,393 bases
Orientation:
Minus strand

Genomic View for HCRT Gene

Genes around HCRT on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCRT Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HCRT Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCRT Gene

Proteins for HCRT Gene

  • Protein details for HCRT Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43612-OREX_HUMAN
    Recommended name:
    Orexin
    Protein Accession:
    O43612

    Protein attributes for HCRT Gene

    Size:
    131 amino acids
    Molecular mass:
    13363 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for HCRT Gene

neXtProt entry for HCRT Gene

Post-translational modifications for HCRT Gene

  • Specific enzymatic cleavages at paired basic residues yield the different active peptides.

Other Protein References for HCRT Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HCRT Gene

Domains & Families for HCRT Gene

Gene Families for HCRT Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for HCRT Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HCRT Gene

GenScript: Design optimal peptide antigens:
  • Hypocretin (OREX_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43612

UniProtKB/Swiss-Prot:

OREX_HUMAN :
  • Belongs to the orexin family.
Family:
  • Belongs to the orexin family.
genes like me logo Genes that share domains with HCRT: view

Function for HCRT Gene

Molecular function for HCRT Gene

UniProtKB/Swiss-Prot Function:
Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity.
GENATLAS Biochemistry:
hypocretin neuropeptide precursor of isoforms A and B,expressed in lateral hypothalamus and adjacent areas,potential mediator in the central feedback mechanism,that regulates feeding behavior,homolog to secretin,susceptibility gene for narcolepsy

Phenotypes From GWAS Catalog for HCRT Gene

Gene Ontology (GO) - Molecular Function for HCRT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005184 neuropeptide hormone activity IEA,IBA 21873635
GO:0031771 type 1 hypocretin receptor binding IBA 21873635
GO:0031772 type 2 hypocretin receptor binding IBA 21873635
genes like me logo Genes that share ontologies with HCRT: view
genes like me logo Genes that share phenotypes with HCRT: view

Human Phenotype Ontology for HCRT Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HCRT Gene

MGI Knock Outs for HCRT:
  • Hcrt Hcrt<tm1Ywa>
  • Hcrt Hcrt<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

miRNA for HCRT Gene

miRTarBase miRNAs that target HCRT

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HCRT

Clone Products

  • Addgene plasmids for HCRT

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for HCRT Gene

Localization for HCRT Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCRT Gene

Rough endoplasmic reticulum. Cytoplasmic vesicle. Cell junction, synapse. Note=Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HCRT gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 3
nucleus 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for HCRT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005737 cytoplasm IEA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005791 rough endoplasmic reticulum IEA --
GO:0008021 synaptic vesicle TAS 9419374
genes like me logo Genes that share ontologies with HCRT: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HCRT Gene

Pathways & Interactions for HCRT Gene

genes like me logo Genes that share pathways with HCRT: view

Pathways by source for HCRT Gene

SIGNOR curated interactions for HCRT Gene

Activates:

Gene Ontology (GO) - Biological Process for HCRT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001659 temperature homeostasis IBA 21873635
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway IEA --
GO:0007204 positive regulation of cytosolic calcium ion concentration IEA --
GO:0007205 protein kinase C-activating G protein-coupled receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with HCRT: view

Drugs & Compounds for HCRT Gene

(44) Drugs for HCRT Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pidolic acid Approved, Investigational Pharma Target 0

(18) Additional Compounds for HCRT Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HCRT: view

Transcripts for HCRT Gene

mRNA/cDNA for HCRT Gene

(1) REFSEQ mRNAs :
(1) Additional mRNA sequences :
(6) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HCRT

Clone Products

  • Addgene plasmids for HCRT

Alternative Splicing Database (ASD) splice patterns (SP) for HCRT Gene

No ASD Table

Relevant External Links for HCRT Gene

GeneLoc Exon Structure for
HCRT
ECgene alternative splicing isoforms for
HCRT

Expression for HCRT Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HCRT Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HCRT Gene

This gene is overexpressed in Brain - Hypothalamus (x51.1).

NURSA nuclear receptor signaling pathways regulating expression of HCRT Gene:

HCRT

SOURCE GeneReport for Unigene cluster for HCRT Gene:

Hs.158348

mRNA Expression by UniProt/SwissProt for HCRT Gene:

O43612-OREX_HUMAN
Tissue specificity: Abundantly expressed in subthalamic nucleus but undetectable in other brain regions tested (hypothalamus was not tested) and in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Evidence on tissue expression from TISSUES for HCRT Gene

  • Nervous system(3.6)
  • Adrenal gland(2.3)
  • Muscle(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HCRT Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
  • mouth
  • pharynx
Thorax:
  • heart
General:
  • blood vessel
  • peripheral nervous system
genes like me logo Genes that share expression patterns with HCRT: view

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for HCRT Gene

Orthologs for HCRT Gene

This gene was present in the common ancestor of chordates.

Orthologs for HCRT Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HCRT 33 32
  • 99.49 (n)
OneToOne
cow
(Bos Taurus)
Mammalia BORX 33
  • 90 (a)
OneToOne
HCRT 32
  • 88.04 (n)
dog
(Canis familiaris)
Mammalia HCRT 33 32
  • 87.18 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hcrt 32
  • 83.92 (n)
mouse
(Mus musculus)
Mammalia Hcrt 17 33 32
  • 80 (n)
oppossum
(Monodelphis domestica)
Mammalia HCRT 33
  • 67 (a)
OneToOne
chicken
(Gallus gallus)
Aves HCRT 33
  • 48 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HCRT 33
  • 43 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii hcrt 33
  • 34 (a)
OneToOne
Species where no ortholog for HCRT was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HCRT Gene

ENSEMBL:
Gene Tree for HCRT (if available)
TreeFam:
Gene Tree for HCRT (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HCRT: view image

Paralogs for HCRT Gene

No data available for Paralogs for HCRT Gene

Variants for HCRT Gene

Sequence variations from dbSNP and Humsavar for HCRT Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
rs104894574 pathogenic, Narcolepsy 1, Narcolepsy 1 (NRCLP1) [MIM:161400] 42,184,503(-) A/C coding_sequence_variant, missense_variant
rs1000249432 -- 42,184,867(-) A/G intron_variant
rs1000855419 -- 42,184,337(-) G/C coding_sequence_variant, synonymous_variant
rs1001729743 -- 42,186,087(-) C/T upstream_transcript_variant
rs1002003152 -- 42,186,766(-) G/C upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for HCRT Gene

Variant ID Type Subtype PubMed ID
nsv1056904 CNV gain 25217958
nsv1146669 OTHER inversion 26484159

Variation tolerance for HCRT Gene

Gene Damage Index Score: 0.73; 15.53% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HCRT Gene

Human Gene Mutation Database (HGMD)
HCRT
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HCRT

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HCRT Gene

Disorders for HCRT Gene

MalaCards: The human disease database

(34) MalaCards diseases for HCRT Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
narcolepsy 1
  • nrclp1
narcolepsy
  • narcolepsy, without cataplexy
sleep disorder
  • non-organic sleep disorder
recurrent hypersomnia
  • primary recurrent hypersomnia
idiopathic hypersomnia
  • idiopathic hypersomnolence
- elite association - COSMIC cancer census association via MalaCards
Search HCRT in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

OREX_HUMAN
  • Narcolepsy 1 (NRCLP1) [MIM:161400]: Neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. {ECO:0000269 PubMed:10973318}. Note=The disease is caused by mutations affecting the gene represented in this entry. Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients.

Additional Disease Information for HCRT

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HCRT: view

No data available for Genatlas for HCRT Gene

Publications for HCRT Gene

  1. Orexin-A is composed of a highly conserved C-terminal and a specific, hydrophilic N-terminal region, revealing the structural basis of specific recognition by the orexin-1 receptor. (PMID: 16429482) Takai T … Ikegami T (Journal of peptide science : an official publication of the European Peptide Society 2006) 3 4 23 56
  2. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. (PMID: 9491897) Sakurai T … Yanagisawa M (Cell 1998) 2 3 4 56
  3. Association study of 182 candidate genes in anorexia nervosa. (PMID: 20468064) Pinheiro AP … Woodside DB (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 43 56
  4. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency. (PMID: 20129934) Knudsen S … Jennum PJ (Brain : a journal of neurology 2010) 3 23 56
  5. A common variant in DRD3 receptor is associated with autism spectrum disorder. (PMID: 19058789) de Krom M … van Ree JM (Biological psychiatry 2009) 3 43 56

Products for HCRT Gene

Sources for HCRT Gene