HCRTR1

hypocretin receptor 1, the group of Hypocretin receptors

Basic information

Region (hg38): 1:31617685-31632518

Links

ENSG00000121764 ∙ NCBI:3061 ∙ OMIM:602392 ∙ HGNC:4848 ∙ Uniprot:O43613 ∙ 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 HCRTR1 gene.

• Inborn genetic diseases (30 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCRTR1 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			24	1	1	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			5	1		6
Total	0	0	29	2	3

Variants in HCRTR1

This is a list of pathogenic ClinVar variants found in the HCRTR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-31619203-C-T		not specified	Uncertain significance (May 09, 2022)
1-31619225-G-A		not specified	Likely benign (Jun 07, 2023)
1-31619239-G-T		not specified	Uncertain significance (Dec 14, 2023)
1-31619274-G-A		not specified	Uncertain significance (Sep 29, 2023)
1-31619386-C-T		not specified	Uncertain significance (Oct 04, 2022)
1-31619542-C-T			Benign (Jan 30, 2018)
1-31619543-G-A		not specified	Uncertain significance (May 08, 2023)
1-31619550-G-A		not specified	Uncertain significance (Oct 26, 2022)
1-31619562-T-C		not specified	Uncertain significance (Oct 27, 2023)
1-31619569-A-G			Benign (May 30, 2018)
1-31619592-A-G		not specified	Uncertain significance (Jul 19, 2023)
1-31619651-G-A		not specified	Uncertain significance (Dec 19, 2022)
1-31619675-G-A		not specified	Uncertain significance (Aug 08, 2023)
1-31620882-A-G		not specified	Uncertain significance (Jun 09, 2022)
1-31620942-C-T		not specified	Uncertain significance (Feb 16, 2023)
1-31621002-G-A		not specified	Uncertain significance (May 31, 2023)
1-31621048-G-A		not specified	Uncertain significance (Nov 09, 2023)
1-31621503-A-G		not specified	Uncertain significance (Oct 26, 2022)
1-31621527-C-G		not specified	Uncertain significance (May 11, 2022)
1-31623526-C-A		not specified	Uncertain significance (Jan 08, 2024)
1-31623550-C-T		not specified	Uncertain significance (Sep 14, 2022)
1-31623551-G-A		not specified	Uncertain significance (Apr 08, 2022)
1-31623607-G-A		not specified	Uncertain significance (Jul 08, 2022)
1-31623620-G-A			Benign (May 08, 2018)
1-31623682-C-A		not specified	Uncertain significance (Jun 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCRTR1	protein_coding	protein_coding	ENST00000403528	7	14833

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000174	0.974	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	215	276	0.780	0.0000176	2724
Missense in Polyphen		48	61.714	0.77778		650
Synonymous	0.376	105	110	0.954	0.00000639	916
Loss of Function	1.99	9	18.2	0.496	8.62e-7	195

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000467	0.000467
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000285	0.000281
Middle Eastern	0.00	0.00
South Asian	0.000719	0.000719
Other	0.000660	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide (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: 0.150

Intolerance Scores

• loftool: 0.633
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.74

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.626
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.251

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hcrtr1
• 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)

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;chemical synaptic transmission;feeding behavior;regulation of cytosolic calcium ion concentration;positive regulation of ERK1 and ERK2 cascade
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: G protein-coupled receptor activity;orexin receptor activity;peptide hormone binding