NCF2

Chr 1AR

neutrophil cytosolic factor 2

Also known as: NCF-2, NOXA2, P67-PHOX, P67PHOX

NCBI Gene: 4688 ENSG00000116701 UniProt: P19878 OMIM: 608515

This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Chronic granulomatous disease 2, autosomal recessiveMIM #233710

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Chronic granulomatous disease 2, autosomal recessive; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — NCF2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.71

OE 0.49 (0.33–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.04Z-score

OE missense 0.82 (0.74–0.92)

225 obs / 273.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.33–0.74)

0≤0.351.4

Missense OE?0.82 (0.74–0.92)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 16 / 32.7Missense obs/exp: 225 / 273.4Syn Z: -0.09

Background carrier burden — how many people carry a rare variant somewhere in NCF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

553 rare PASS variants

Rare truncating (LoF)

1 in 1,600

116 rare PASS variants

Rare synonymous (reference)

1 in 210

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NCF2. 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 140	1 in 1,700
South Asian	~43k	1 in 82	1 in 1,600
Remaining (unassigned)	~30k	1 in 99	1 in 1,300
European (Finnish)	~27k	1 in 270	1 in 3,000
Admixed American	~22k	1 in 80	1 in 470
African / African American	~21k	1 in 97	1 in 1,100
East Asian	~20k	1 in 110	1 in 900
Ashkenazi Jewish	~13k	1 in 390	none seen
Middle Eastern	~2,884	1 in 83	none seen

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 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓