NCF1

Chr 7AR

neutrophil cytosolic factor 1

Also known as: CGD1, NCF-1, NCF-47K, NCF1A, NOXO2, SH3PXD1A, p47-phox, p47phox

NCBI Gene: 653361ENSG00000158517UniProt: P14598

The protein encoded by this gene is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is a multicomponent enzyme that is activated to produce superoxide anion. Mutations in this gene have been associated with chronic granulomatous disease. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Chronic granulomatous disease 1, autosomal recessiveMIM #233700
AR
149
ClinVar variants
81
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— NCF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
81 Pathogenic / Likely Pathogenic· 43 VUS of 149 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.13LOEUF
pLI 0.000
Z-score 1.21
OE 0.65 (0.39–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.01Z-score
OE missense 0.77 (0.66–0.90)
113 obs / 147.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.39–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.66–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 9 / 13.9Missense obs/exp: 113 / 147.6Syn Z: 0.91

ClinVar Variant Classifications

149 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic6
VUS43
Likely Benign14
Benign10
Conflicting1
75
Pathogenic
6
Likely Pathogenic
43
VUS
14
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
3
68
0
75
Likely Pathogenic
1
0
5
0
6
VUS
0
33
9
1
43
Likely Benign
0
2
2
10
14
Benign
0
2
7
1
10
Conflicting
—1
Total5409112149

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

View in ClinVar →

Protein Context — Lollipop Plot

NCF1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NCF1-related chronic granulomatous disease cytochrome b positive

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Chronic granulomatous disease 1, autosomal recessive

MIM #233700

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NCF1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH.
Zhang J et al.·Cell Metab
2024
Chronic Granulomatous Disease.
Roos D·Methods Mol Biol
2019Review
Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1(+) monocytes-derived macrophages.
Yuan X et al.·Ann Rheum Dis
2025Cohort
Targeting S100A8/A9-NCF1 axis in tumor microenvironment to prevent tumor metastasis by self-assembled peptide nanofibers.
Guo Y et al.·Mol Ther
2025
Neutrophil infiltration associated genes on the prognosis and tumor immune microenvironment of lung adenocarcinoma.
Liu R et al.·Front Immunol
2023
Reliable genetic diagnosis of NCF1 (p47(phox))-deficient chronic granulomatous disease using high-throughput sequencing.
Hsu AP et al.·Front Immunol
2025
Prime Editing: The Next Frontier in Precision Gene Therapy.
Aliciaslan M et al.·J Gene Med
2025Review
Integration analysis of transcriptomics revealed NETosis heterogeneity and Ncf1 as a prognostic biomarker in neutrophil asthma.
Yan Q et al.·Int Immunopharmacol
2025
NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions.
Luo H et al.·JCI Insight
2023
Human SLE variant NCF1-R90H promotes kidney damage and murine lupus through enhanced Tfh2 responses induced by defective efferocytosis of macrophages.
Geng L et al.·Ann Rheum Dis
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
p47Autosomal RecessiveChronic Granulomatous Disease

pCCLCHIM-p47 (Lentiviral Vector Transduced CD34 Plus Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)

ENROLLING BY INVITATION
NCT06253507Phase PHASE1, PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2024-06-25
Cryopreserved Autologous CD34+ cells transduced with pCCLCHIM-p47
Chronic Granulomatous DiseaseGranulomatous Disease, Chronic

A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD )

ACTIVE NOT RECRUITING
NCT06559176Phase PHASE1, PHASE2Prime Medicine, Inc.Started 2024-10-17
PM359
P47-Phox, Deficiency of

Lentiviral Gene Therapy for p47 AR-CGD

RECRUITING
NCT05207657Phase PHASE1, PHASE2Great Ormond Street Hospital for Children NHS Foundation TrustStarted 2023-03-20
Lentiviral vector transduced CD34+ cells

External Resources

Links to major genomics databases and tools