NQO1

protein-coding

NAD(P)H quinone dehydrogenase 1

Gene summary

This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Previous symbols:

NMOR1
DIA4

MANE transcript

NM_000903.3

Inheritance

—

ClinVar variants

P:2U:134B:134

Top phenotype

Primary ciliary dyskinesia

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr16:69,706,996-69,726,668

External References & Databases

Ensembl (ENSG00000181019)

Transcript & Mutation Effects

hg38 • Region Span ~19.7 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 NQO1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 265

not providedTotal: 4

Primary ciliary dyskinesiaTotal: 2

NQO1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000903.3. 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				129 clinvar		129
missense		1 clinvar	131 clinvar	5 clinvar		137
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	2	134	134	0	270

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000903.3	RefSeq	NP_000894.1	6	MANE Select
ENST00000320623.10	Ensembl	ENSP00000319788.5	6	MANE Select
NM_001025433.2	RefSeq	NP_001020604.1	5	Standard
NM_001025434.2	RefSeq	NP_001020605.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human)
Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
Hepatocellular carcinoma - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)
Doxorubicin Pathway, Pharmacokinetics

Biological Process

regulation of cellular amino acid metabolic process
xenobiotic metabolic process
nitric oxide biosynthetic process
synaptic transmission, cholinergic
aging

Molecular Function

RNA binding
NAD(P)H dehydrogenase (quinone) activity
cytochrome-b5 reductase activity, acting on NAD(P)H
superoxide dismutase activity
protein binding

Cellular Component

cytoplasm
cytosol
dendrite
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320623
Coding exons: 6
Length: 19956
Individuals with no LoFs: 124869
Homozygous LoFs: 12
Heterozygous LoFs: 866
Defined: 125747
p: 0.00350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	106	150	0.705	0.00000768	1803
Missense (PolyPhen)		35	58.312	0.60022		687
Synonymous	-0.0322	58	57.7	1.01	0.00000338	516
Loss of Function	0.113	14	14.5	0.968	7.88e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0.037	0.037	notable
Latino/Admixed American	0.0042	0.0042	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00074	0.00074	rare
European (Non-Finnish)	0.00081	0.00081	rare
South Asian	0.00026	0.00026	rare
Other	0.0031	0.0031	notable

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.755

Intolerance Scores

LoFtool: 0.989
RVIS EVS: 0.55
RVIS percentile EVS: 81.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.989

Gene Damage Prediction

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