NQO2

protein-coding

N-ribosyldihydronicotinamide:quinone reductase 2

Gene summary

This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

Previous symbols:

NMOR2

MANE transcript

NM_000904.6

Inheritance

—

ClinVar variants

U:40B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr6:2,987,987-3,019,755

External References & Databases

Ensembl (ENSG00000124588)

Transcript & Mutation Effects

hg38 • Region Span ~31.8 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 NQO2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000904.6. 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
missense			37 clinvar	2 clinvar		39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	40	2	0	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 198 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000904.6	RefSeq	NP_000895.2	6	MANE Select
ENST00000380455.11	Ensembl	ENSP00000369822.4	6	MANE Select
NM_001290221.2	RefSeq	NP_001277150.1	6	Standard
NM_001290222.2	RefSeq	NP_001277151.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling
Phase I - Functionalization of compounds
Biological oxidations
Metabolism

Biological Process

xenobiotic metabolic process
electron transport chain
oxidation-reduction process

Molecular Function

dihydronicotinamide riboside quinone reductase activity
NAD(P)H dehydrogenase (quinone) activity
protein binding
zinc ion binding
electron transfer activity

Cellular Component

nucleoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338130
Coding exons: 6
Length: 31776
Individuals with no LoFs: 125703
Homozygous LoFs: 1
Heterozygous LoFs: 44
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.475	118	133	0.884	0.00000741	1508
Missense (PolyPhen)		52	55.572	0.93572		669
Synonymous	-0.580	62	56.5	1.10	0.00000380	441
Loss of Function	0.384	10	11.4	0.877	5.49e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. {ECO:0000269|PubMed:18254726}.;

Recessive Scores

pRec: 0.229

Intolerance Scores

LoFtool: 0.817
RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.890

Gene Damage Prediction

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