HCRT

hypocretin neuropeptide precursor, the group of Neuropeptides

Basic information

Region (hg38): 17:42184060-42185452

Links

ENSG00000161610 ∙ NCBI:3060 ∙ OMIM:602358 ∙ HGNC:4847 ∙ Uniprot:O43612 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• narcolepsy 1 (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Narcolepsy 1	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10973318

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HCRT gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCRT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			9	1		10
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	4	0

Variants in HCRT

This is a list of pathogenic ClinVar variants found in the HCRT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-42184174-C-T		not specified	Uncertain significance (Feb 05, 2024)
17-42184183-C-T			Uncertain significance (Nov 01, 2021)
17-42184191-G-T		not specified	Uncertain significance (Dec 22, 2023)
17-42184206-C-T		not specified	Uncertain significance (Nov 18, 2023)
17-42184208-G-C		HCRT-related disorder	Likely benign (Aug 29, 2019)
17-42184216-C-A		not specified	Uncertain significance (Nov 02, 2023)
17-42184224-G-A		not specified	Uncertain significance (Jan 09, 2024)
17-42184227-C-T		not specified	Uncertain significance (May 26, 2023)
17-42184247-T-A		HCRT-related disorder	Likely benign (Oct 05, 2020)
17-42184347-T-C		HCRT-related disorder	Likely benign (Apr 09, 2019)
17-42184354-G-T		not specified	Uncertain significance (Nov 15, 2021)
17-42184480-G-A		not specified	Uncertain significance (Jun 02, 2023)
17-42184482-G-GGCA		HCRT-related disorder	Likely benign (Feb 22, 2019)
17-42184503-A-C		Narcolepsy 1	Pathogenic (Sep 01, 2000)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCRT	protein_coding	protein_coding	ENST00000293330	2	1393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0288	0.602	125691	0	3	125694	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.758	37	52.5	0.705	0.00000239	773
Missense in Polyphen		17	25.724	0.66086		338
Synonymous	1.10	19	26.2	0.726	0.00000133	317
Loss of Function	0.149	2	2.24	0.892	9.56e-8	28

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000870	0.0000616
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000676	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: 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.
• Pathway: Signaling by GPCR;Signal Transduction;Orexin and neuropeptides FF and QRFP bind to their respective receptors;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.343

Haploinsufficiency Scores

• pHI: 0.149
• hipred: N
• hipred_score: 0.324
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hcrt
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: hcrt
• Affected structure: behavior
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: temperature homeostasis;G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;protein kinase C-activating G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;chemical synaptic transmission;negative regulation of DNA replication;regulation of signaling receptor activity;eating behavior;negative regulation of potassium ion transport;regulation of neurotransmitter secretion;positive regulation of calcium ion transport;negative regulation of transmission of nerve impulse;positive regulation of transmission of nerve impulse;excitatory postsynaptic potential;positive regulation of cold-induced thermogenesis
• Cellular component: extracellular region;rough endoplasmic reticulum;synaptic vesicle;cell junction;secretory granule;perinuclear region of cytoplasm;postsynapse
• Molecular function: neuropeptide hormone activity;type 1 hypocretin receptor binding;type 2 hypocretin receptor binding