HCRT (hypocretin neuropeptide precursor)

Gene

• Entrez ID: 3060
• Gene name: Hypocretin neuropeptide precursor
• Gene symbol: HCRT
• Synonyms: NRCLP1, OX, PPOX
• Chromosome: 17
• Chromosome location: 17q21.2
• Summary: 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, funct

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894574	A>C	Pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2008883	hsa-miR-4314	CLIP-seq
MIRT2008884	hsa-miR-4436a	CLIP-seq
MIRT2008885	hsa-miR-4488	CLIP-seq
MIRT2008886	hsa-miR-4656	CLIP-seq
MIRT2008887	hsa-miR-4667-5p	CLIP-seq
MIRT2008888	hsa-miR-4697-5p	CLIP-seq
MIRT2008889	hsa-miR-4700-5p	CLIP-seq
MIRT2008890	hsa-miR-637	CLIP-seq
MIRT2008883	hsa-miR-4314	CLIP-seq
MIRT2008885	hsa-miR-4488	CLIP-seq
MIRT2008886	hsa-miR-4656	CLIP-seq
MIRT2008887	hsa-miR-4667-5p	CLIP-seq
MIRT2008888	hsa-miR-4697-5p	CLIP-seq
MIRT2008889	hsa-miR-4700-5p	CLIP-seq
MIRT2008890	hsa-miR-637	CLIP-seq
MIRT2008883	hsa-miR-4314	CLIP-seq
MIRT2008885	hsa-miR-4488	CLIP-seq
MIRT2008886	hsa-miR-4656	CLIP-seq
MIRT2008887	hsa-miR-4667-5p	CLIP-seq
MIRT2008888	hsa-miR-4697-5p	CLIP-seq
MIRT2008889	hsa-miR-4700-5p	CLIP-seq
MIRT2008890	hsa-miR-637	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001659	Process	Temperature homeostasis	IBA	21873635
GO:0005184	Function	Neuropeptide hormone activity	IBA	21873635
GO:0005576	Component	Extracellular region	TAS
GO:0005791	Component	Rough endoplasmic reticulum	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IEA
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IEA
GO:0007205	Process	Protein kinase C-activating G protein-coupled receptor signaling pathway	IEA
GO:0007218	Process	Neuropeptide signaling pathway	IEA
GO:0007268	Process	Chemical synaptic transmission	TAS	9419374
GO:0008021	Component	Synaptic vesicle	TAS	9419374
GO:0008156	Process	Negative regulation of DNA replication	IEA
GO:0030141	Component	Secretory granule	IEA
GO:0030431	Process	Sleep	IBA	21873635
GO:0031771	Function	Type 1 hypocretin receptor binding	IBA	21873635
GO:0031772	Function	Type 2 hypocretin receptor binding	IBA	21873635
GO:0042594	Process	Response to starvation	IBA	21873635
GO:0042755	Process	Eating behavior	IBA	21873635
GO:0043267	Process	Negative regulation of potassium ion transport	IEA
GO:0046928	Process	Regulation of neurotransmitter secretion	IBA	21873635
GO:0048471	Component	Perinuclear region of cytoplasm	IBA	21873635
GO:0051928	Process	Positive regulation of calcium ion transport	IEA
GO:0051970	Process	Negative regulation of transmission of nerve impulse	IEA
GO:0051971	Process	Positive regulation of transmission of nerve impulse	IBA	21873635
GO:0060079	Process	Excitatory postsynaptic potential	IEA
GO:0098794	Component	Postsynapse	IEA
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	23700511

Other IDs

• MIM: 602358
• HGNC: 4847
• e!Ensembl: ENSG00000161610

Protein

• UniProt ID: O43612
• Protein name: Hypocretin neuropeptide precursor (Hypocretin) (Hcrt) (Orexin precursor) (Prepro-orexin) (Preprohypocretin) [Cleaved into: Orexin-A (Hypocretin-1) (Hcrt1); Orexin-B (Hypocretin-2) (Hcrt2)]
• Protein 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 home
• PDB: 1CQ0, 1R02, 1UVQ, 1WSO, 7L1U
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02072	Orexin	1 → 130	Prepro-orexin	Family

• Sequence:

  MNLPSTKVSWAAVTLLLLLLLLPPALLSSGAAAQPLPDCCRQKTCSCRLYELLHGAGNHA
  AGILTLGKRRSGPPGLQGRLQRLLQASGNHAAGILTMGRRAGAEPAPRPCLGRRCSAPAA
  ASVAPGGQSGI

• Sequence length: 131

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Hormone signaling

Reactome:

Orexin and neuropeptides FF and QRFP bind to their respective receptors
G alpha (q) signalling events

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Narcolepsy	Narcolepsy, Narcolepsy 1, Narcolepsy type 1, Narcolepsy type 2	rs104894574, rs387906655	10973318, 23643651, 10973318
Obesity	Obesity	rs34911341, rs74315349, rs1474810899, rs2282440, rs2491132, rs121918111, rs796065034, rs753856820, rs796065035, rs121918112, rs104894023, rs137852821, rs1580764441, rs137852822, rs137852823, rs137852824, rs13447324, rs121913562, rs121913564, rs74315393, rs121913556, rs2989924, rs193922650, rs193922685, rs193922687, rs751160202, rs1421085, rs747681609, rs1553400259, rs13447339, rs370479598, rs1554394014, rs1553174844, rs756232889, rs369841551, rs1557670950, rs1571321748, rs148538980, rs1572820988, rs1591461970, rs1419374563, rs745921568, rs144159890, rs1570714352, rs779783209, rs1573250294, rs1573254045, rs1580744791, rs1580746829, rs6548238, rs7138803, rs7754840

Unknown
Disease name	Disease term	dbSNP ID	References
Amnesia	Amnesia, Transient Global
Cataplexy	Cataplexy
Degenerative diseases, central nervous system	Degenerative Diseases, Central Nervous System, Degenerative Diseases, Spinal Cord		23246865
Hallucinations	Hallucinations, Hallucinations, Hypnapompic
Mental depression	Mental Depression, Depressive disorder	rs587778876, rs587778877	25190041, 24874707, 23510906, 24485472, 23398442, 23510906, 24874707, 23398442, 24485472, 25190041
Narcolepsy-cataplexy syndrome	Narcolepsy-Cataplexy Syndrome		10973318, 23643651
Neurodegenerative disorders	Neurodegenerative Disorders		23246865
Paroxysmal drowsiness	Paroxysmal drowsiness