HCRTR1

protein-coding

hypocretin receptor 1, the group of Hypocretin receptors

Gene summary

The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein selectively binds the hypothalamic neuropeptide orexin A. A related gene (HCRTR2) encodes a G-protein coupled receptor that binds orexin A and orexin B. [provided by RefSeq, Jan 2009]

MANE transcript

NM_001525.3

Inheritance

—

ClinVar variants

U:57B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr1:31,617,686-31,632,518

External References & Databases

Ensembl (ENSG00000121764)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HCRTR1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001525.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			55 clinvar	2 clinvar	1 clinvar	58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	57	2	3	62

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001525.3	RefSeq	NP_001516.2	7	MANE Select
ENST00000403528.7	Ensembl	ENSP00000384387.2	7	MANE Select
ENST00000373705.1	Ensembl	ENSP00000362809.1	7	Standard
ENST00000373706.10	Ensembl	ENSP00000362810.5	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
Peptide GPCRs
GPCRs, Class A Rhodopsin-like
Signaling by GPCR
Signal Transduction

Biological Process

G protein-coupled receptor signaling pathway
neuropeptide signaling pathway
chemical synaptic transmission
feeding behavior
regulation of cytosolic calcium ion concentration

Molecular Function

G protein-coupled receptor activity
orexin receptor activity
peptide hormone binding

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403528
Coding exons: 7
Length: 14833
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125748
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.30	215	276	0.780	0.0000176	2724
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00072	0.00072	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.633
RVIS EVS: 0.15
RVIS percentile EVS: 64.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.251

Gene Damage Prediction

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