OPRK1

protein-coding

opioid receptor kappa 1, the group of Opioid receptors

Gene summary

This gene encodes an opioid receptor, which is a member of the 7 transmembrane-spanning G protein-coupled receptor family. It functions as a receptor for endogenous ligands, as well as a receptor for various synthetic opioids. Ligand binding results in inhibition of adenylate cyclase activity and neurotransmitter release. This opioid receptor plays a role in the perception of pain and mediating the hypolocomotor, analgesic and aversive actions of synthetic opioids. Variations in this gene have also been associated with alcohol dependence and opiate addiction. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

MANE transcript

NM_000912.5

Inheritance

—

ClinVar variants

U:44B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr8:53,225,724-53,251,637

External References & Databases

Ensembl (ENSG00000082556)

Transcript & Mutation Effects

hg38 • Region Span ~25.9 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 OPRK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000912.5. 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	2 clinvar	4
missense			44 clinvar	2 clinvar	2 clinvar	48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	44	4	4	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000912.5	RefSeq	NP_000903.2	3	MANE Select
ENST00000265572.8	Ensembl	ENSP00000265572.3	3	MANE Select
NM_001282904.2	RefSeq	NP_001269833.1	2	Standard
NM_001318497.2	RefSeq	NP_001305426.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
Nalbuphine Action Pathway
Peptide GPCRs
Chemical Compounds to monitor Proteins
MECP2 and Associated Rett Syndrome

Biological Process

immune response
G protein-coupled receptor signaling pathway
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
phospholipase C-activating G protein-coupled receptor signaling pathway
neuropeptide signaling pathway

Molecular Function

G protein-coupled receptor activity
opioid receptor activity
protein binding
receptor serine/threonine kinase binding
dynorphin receptor activity

Cellular Component

nucleus
cytosol
plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265572
Coding exons: 3
Length: 25974
Individuals with no LoFs: 125653
Homozygous LoFs: 0
Heterozygous LoFs: 95
Defined: 125748
p: 0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.464	216	236	0.915	0.0000133	2506
Missense (PolyPhen)		99	122.32	0.80936		1327
Synonymous	-0.680	102	93.6	1.09	0.00000517	771
Loss of Function	0.836	8	11.0	0.728	5.57e-7	122

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00063	0.00062	rare
South Asian	0.00016	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions. {ECO:0000269|PubMed:12004055, ECO:0000269|PubMed:22437504, ECO:0000269|PubMed:7624359, ECO:0000269|PubMed:8060324}.;

Recessive Scores

pRec: 0.244

Intolerance Scores

LoFtool: 0.560
RVIS EVS: -0.29
RVIS percentile EVS: 33.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

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