NQO2

Chr 6ADSomatic

N-ribosyldihydronicotinamide:quinone dehydrogenase 2

Also known as: DHQV, DIA6, NMOR2, QR2

NCBI Gene: 4835 ENSG00000124588 UniProt: P16083 OMIM: 160998

The NQO2 protein is a cytosolic flavoprotein that catalyzes two-electron reduction of quinones and functions in detoxification pathways and vitamin K-dependent processes including prothrombin synthesis. Mutations are associated with breast cancer susceptibility with autosomal dominant inheritance. The gene is not highly constrained against loss-of-function variants (pLI near 0, LOEUF 1.48).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{?Breast cancer susceptibility}MIM #114480

ADSomatic

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.48

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.48LOEUF

pLI 0.000

Z-score 0.38

OE 0.88 (0.54–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.47Z-score

OE missense 0.88 (0.76–1.03)

118 obs / 133.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.54–1.48)

0≤0.351.4

Missense OE?0.88 (0.76–1.03)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 10 / 11.4Missense obs/exp: 118 / 133.4Syn Z: -0.58

Background carrier burden — how many people carry a rare variant somewhere in NQO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

299 rare PASS variants

Rare truncating (LoF)

1 in 1,000

45 rare PASS variants

Rare synonymous (reference)

1 in 320

129 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NQO2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 300	1 in 950
South Asian	~43k	1 in 220	1 in 3,600
Remaining (unassigned)	~30k	1 in 170	1 in 790
European (Finnish)	~27k	1 in 680	none seen
Admixed American	~22k	1 in 180	1 in 2,000
African / African American	~21k	1 in 94	1 in 1,600
East Asian	~20k	1 in 100	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 480	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓