HCRTR2

hypocretin receptor 2, the group of Hypocretin receptors

Basic information

Region (hg38): 6:55106460-55282617

Links

ENSG00000137252 ∙ NCBI:3062 ∙ OMIM:602393 ∙ HGNC:4849 ∙ Uniprot:O43614 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HCRTR2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCRTR2 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	3	5
missense			23	3	1	27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	5	4

Variants in HCRTR2

This is a list of pathogenic ClinVar variants found in the HCRTR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-55174615-C-T		HCRTR2-related disorder	Likely benign (Aug 09, 2022)
6-55174617-C-T		HCRTR2-related disorder	Likely benign (Jun 20, 2019)
6-55174628-A-G		not specified	Uncertain significance (Apr 17, 2023)
6-55174745-A-G		not specified	Uncertain significance (Jun 07, 2023)
6-55174750-T-C		not specified	Uncertain significance (Jan 26, 2023)
6-55174766-G-T		not specified	Uncertain significance (Feb 02, 2024)
6-55174792-C-T		not specified	Uncertain significance (Jun 09, 2022)
6-55174800-G-A		HCRTR2-related disorder	Likely benign (Jun 04, 2019)
6-55248710-G-T		not specified	Uncertain significance (Dec 27, 2023)
6-55248729-T-C		not specified	Uncertain significance (Mar 14, 2023)
6-55255177-C-T		HCRTR2-related disorder	Benign (May 01, 2019)
6-55255242-G-A		not specified	Uncertain significance (Aug 30, 2022)
6-55255280-A-G		not specified	Uncertain significance (Dec 07, 2021)
6-55255310-T-A		HCRTR2-related disorder	Likely benign (Dec 21, 2022)
6-55255335-C-G		not specified	Uncertain significance (Mar 06, 2023)
6-55255370-C-T		not specified	Uncertain significance (Aug 04, 2023)
6-55263736-T-G		not specified	Uncertain significance (Aug 31, 2022)
6-55263796-A-G		not specified	Uncertain significance (Jun 27, 2023)
6-55263803-G-T		not specified	Uncertain significance (Aug 16, 2021)
6-55277395-T-A		not specified	Uncertain significance (Jan 17, 2023)
6-55277444-G-A		not specified	Uncertain significance (Dec 02, 2022)
6-55277463-G-A		HCRTR2-related disorder	Benign (Dec 31, 2019)
6-55277539-A-G		HCRTR2-related disorder	Benign (Oct 16, 2019)
6-55277581-A-G		not specified	Uncertain significance (Dec 19, 2023)
6-55282275-G-C		not specified	Uncertain significance (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCRTR2	protein_coding	protein_coding	ENST00000370862	7	108369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00504	0.994	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.984	210	254	0.826	0.0000140	2887
Missense in Polyphen		36	74.88	0.48077		851
Synonymous	-1.74	115	93.6	1.23	0.00000514	883
Loss of Function	2.86	8	22.7	0.353	0.00000126	235

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000883	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000982	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides (PubMed:9491897, PubMed:26950369). Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding (PubMed:9491897, PubMed:26950369). {ECO:0000269|PubMed:26950369, ECO:0000269|PubMed:9491897}.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Peptide GPCRs;GPCRs, Class A Rhodopsin-like;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: 0.119

Intolerance Scores

• loftool: 0.592
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.63

Haploinsufficiency Scores

• pHI: 0.167
• hipred: Y
• hipred_score: 0.663

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0391

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hcrtr2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype

Zebrafish Information Network

• Gene name: hcrtr2
• Affected structure: circadian sleep/wake cycle, sleep
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;chemical synaptic transmission;feeding behavior;regulation of circadian sleep/wake cycle, wakefulness;circadian sleep/wake cycle process;regulation of cytosolic calcium ion concentration
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: G protein-coupled receptor activity;neuropeptide receptor activity;orexin receptor activity;peptide hormone binding