HCRTR2

protein-coding

hypocretin receptor 2, 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 binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]

MANE transcript

NM_001384272.1

Inheritance

—

ClinVar variants

U:46B:9

Top phenotype

HCRTR2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr6:55,106,460-55,282,617

External References & Databases

Ensembl (ENSG00000137252)

Transcript & Mutation Effects

hg38 • Region Span ~176.2 kb

Loading mutation effect viewer...

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 HCRTR2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 46

HCRTR2-related disorderTotal: 7

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001384272.1. 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				2 clinvar	3 clinvar	5
missense			46 clinvar	4 clinvar		50
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	6	3	55

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001384272.1	RefSeq	NP_001371201.1	7	MANE Select
ENST00000370862.4	Ensembl	ENSP00000359899.3	7	MANE Select
NM_001526.5	RefSeq	NP_001517.2	7	Standard
ENST00000615358.4	Ensembl	ENSP00000477548.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
hcrtr2	Danio rerio	Structure: circadian sleep/wake cycle, sleep Quality: disrupted abnormal

Gene / Model

Organism

Observed Phenotype

hcrtr2

Danio rerio

Structure: circadian sleep/wake cycle, sleep

Quality: disrupted

abnormal

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
phospholipase C-activating G protein-coupled receptor signaling pathway
neuropeptide signaling pathway
chemical synaptic transmission
feeding behavior

Molecular Function

G protein-coupled receptor activity
neuropeptide 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: ENST00000370862
Coding exons: 7
Length: 108369
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.984	210	254	0.826	0.0000140	2887
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.592
RVIS EVS: 0.71
RVIS percentile EVS: 85.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0391

Gene Damage Prediction

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