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
  • PPOX 2 3 4
  • OX 2 3 4
  • Prepro-Orexin 2 3
  • Hypocretin (Orexin) Neuropeptide Precursor 2
  • Hypocretin (Orexin) Neuropeptide 3
  • Hypocretin 4
  • NRCLP1 3
  • PPORX 4
  • HCRT 5
  • 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 Signaling by GPCR and Peptide ligand-binding receptors. 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.

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 Pubs

Promoters and enhancers for HCRT Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J042120 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 11.1 +63.7 63726 3.1 IKZF1 ZNF600 MYC SIX5 KLF9 POLR2A CEBPA YY1 MXD4 SMAD5 HSPB9 KAT2A piR-30173 DHX58 ZNF385C KCNH4 HCRT ENSG00000267261
GH17J042515 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 10.1 -336.4 -336441 12.2 MYC ZNF600 IKZF1 NCOR1 ZNF654 SSRP1 JUND ZNF592 KLF9 CEBPA lnc-PSMC3IP-4 MLX TUBG2 ENSG00000267002 CAVIN1 NAGLU ENSG00000267340 RAB5C KAT2A ATP6V0A1
GH17J042110 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 11.3 +73.1 73050 3.3 BCLAF1 ZNF207 MYC SSRP1 POLR2A ZNF223 NFIC YY1 SMAD5 MNT DHX58 piR-57781 CNP KCNH4 HCRT RAB5C IFI35 AOC4P KAT2A lnc-ZNF385C-8
GH17J042245 Enhancer 1.7 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 10.3 -65.9 -65877 11 ZNF600 ZNF580 ZMYM3 KLF9 POLR2A CEBPA ZNF10 ZSCAN16 ZIC2 CHD4 STAT5B HCRT KCNH4 ATP6V0A1 CNP STAT5A STAT3 MLX EZH1 DHX58
GH17J042128 Promoter/Enhancer 1.5 Ensembl ENCODE dbSUPER 11.5 +52.5 52491 8.4 NCOR1 ZNF600 IKZF1 CEBPA ATF3 ZSCAN16 NFIC ZIC2 YY1 KLF11 DHX58 CNP HSPB9 CNTD1 NBR2 RETREG3 RAB5C KCNH4 HCRT ZNF385C
- 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 the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HCRT

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

Latest Assembly
chr17:42,184,060-42,185,452
(GRCh38/hg38)
Size:
1,393 bases
Orientation:
Minus strand

Previous Assembly
chr17:40,336,078-40,337,470
(GRCh37/hg19 by Entrez Gene)
Size:
1,393 bases
Orientation:
Minus strand

chr17:40,336,078-40,337,470
(GRCh37/hg19 by Ensembl)
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

InterPro:
Blocks:
  • Prepro-orexin signature

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>

miRNA for HCRT Gene

miRTarBase miRNAs that target HCRT

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products 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 4
nucleus 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
cytosol 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 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

(45) 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

(17) 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 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

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

Expression for HCRT Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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(3.5)
  • Adrenal gland(2.8)
  • Muscle(2.8)
  • Heart(2.5)
  • Pancreas(2.4)
  • Thyroid gland(2.4)
  • Skin(2.4)
  • Blood(2.2)
  • Stomach(2.1)

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

Primer products for research

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 29 30
  • 99.49 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia BORX 30
  • 90 (a)
OneToOne
HCRT 29
  • 88.04 (n)
Dog
(Canis familiaris)
Mammalia HCRT 29 30
  • 87.18 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hcrt 29
  • 83.92 (n)
Mouse
(Mus musculus)
Mammalia Hcrt 29 16 30
  • 80 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HCRT 30
  • 67 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HCRT 30
  • 48 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HCRT 30
  • 43 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii hcrt 30
  • 34 (a)
OneToOne
Species where no ortholog for HCRT was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (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
Alliance of Genome Resources:
Additional Orthologs for HCRT

Paralogs for HCRT Gene

No data available for Paralogs for HCRT Gene

Variants for HCRT Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HCRT Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
rs104894574 Pathogenic: Narcolepsy 1. Narcolepsy 1 (NRCLP1) [MIM:161400] 42,184,503(-) A/Cp.Leu16Arg
NM_001524.1(HCRT):c.47T>G (p.Leu16Arg)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HCRT Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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
Leiden Open Variation Database (LOVD)
HCRT

SNP Genotyping and Copy Number Assays for research

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

Disorders for HCRT Gene

MalaCards: The human disease database

(62) MalaCards diseases for HCRT Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
narcolepsy 1
  • nrclp1
narcolepsy
  • narcolepsy, without cataplexy
recurrent hypersomnia
  • primary recurrent hypersomnia
narcolepsy 2
  • narcolepsy 2, susceptibility to
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 variants 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

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HCRT: view

No data available for Genatlas for HCRT Gene

Publications for HCRT Gene

  1. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. (PMID: 10973318) Peyron C … Mignot E (Nature medicine 2000) 3 4 22 72
  2. 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 22
  3. Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. (PMID: 15978554) Meerabux J … Yoshikawa T (Biological psychiatry 2005) 3 22 40
  4. Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B. (PMID: 10583376) Lee JH … Lee W (European journal of biochemistry 1999) 3 4 22
  5. 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

Products for HCRT Gene

  • Addgene plasmids for HCRT

Sources for HCRT Gene