NCF2

Chr 1

neutrophil cytosolic factor 2

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

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]

GeneReviewsResearchGenerating clinical summary…
LOFmechanismLOEUF 0.74
Clinical SummaryNCF2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 184 VUS of 685 total submissions
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GeneReview available — NCF2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.74LOEUF
pLI 0.000
Z-score 2.71
OE 0.49 (0.330.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.04Z-score
OE missense 0.82 (0.740.92)
225 obs / 273.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.49 (0.330.74)
00.351.4
Missense OE?0.82 (0.740.92)
00.61.4
Synonymous OE?1.01
01.21.6
LoF obs/exp: 16 / 32.7Missense obs/exp: 225 / 273.4Syn Z: -0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNCF2-related chronic granulomatous disease cytochrome b positive type IILOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.6540th %ile
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

685 submitted variants in ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic33
VUS184
Likely Benign329
Benign42
Conflicting22
49
Pathogenic
33
Likely Pathogenic
184
VUS
329
Likely Benign
42
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
35
3
11
0
49
Likely Pathogenic
28
4
1
0
33
VUS
7
158
16
3
184
Likely Benign
1
10
175
143
329
Benign
0
2
38
2
42
Conflicting
22
Total71177241148659

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap NCF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NCF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →