GeneBe

NCF1

protein-coding

neutrophil cytosolic factor 1

Gene summary

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]

MANE transcript

NM_000265.7

Inheritance

AR

ClinVar variants

P:16U:41B:29

Top phenotype

Granulomatous disease, chronic, autosomal recessive, 1

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr7:74,774,011-74,789,315

External References & Databases

Ensembl (ENSG00000158517)NCBI Gene (653361)OMIM (608512)HGNC:7660GenCCUniProt (P14598)AlphaFoldClinVar (NCF1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~15.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

chronic granulomatous diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018305

Submitter: Orphanet

granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009309

Submitter: Labcorp Genetics (formerly Invitae)

granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009309

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Granulomatous disease, chronic, autosomal recessive, 1AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation

Refs: 5755008; 6848934; 3011845; 3339133; 2770793; 2011585; 11060536; 10706888; 11133775; 16972229; 19329991; 22157170; 22876374; 22924696Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCF1 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 34
Inborn genetic diseasesTotal: 31
not specifiedTotal: 30
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1Total: 19
NCF1-related disordersTotal: 6
Granulomatous disease, chronic, X-linkedTotal: 2
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2Total: 1
Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000265.7. 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.

EffectPLPVUSLBBSum
synonymous
21
clinvar
 21
missense
2
clinvar
1
clinvar
39
clinvar
7
clinvar
1
clinvar
 50
nonsense
2
clinvar
2
clinvar
 4
start loss
0
frameshift
3
clinvar
5
clinvar
2
clinvar
 10
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total794128186

Highest pathogenic variant AF is 0.00038657474

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000265.7RefSeqNP_000256.411MANE Select
ENST00000289473.11EnsemblENSP00000289473.411MANE Select
ENST00000433458.5EnsemblENSP00000392870.26Standard
ENST00000442021.6EnsemblENSP00000401935.35Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ncf1Danio rerio

Structure: respiratory burst

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Fc gamma R-mediated phagocytosis - Homo sapiens (human)
  • Phagosome - Homo sapiens (human)
  • Chemokine signaling pathway - Homo sapiens (human)
  • Fluid shear stress and atherosclerosis - Homo sapiens (human)
  • Leishmaniasis - Homo sapiens (human)

Biological Process

  • protein targeting to membrane
  • superoxide metabolic process
  • apoptotic process
  • cellular defense response
  • positive regulation of phosphatidylinositol 3-kinase signaling

Molecular Function

  • protein binding
  • electron transfer activity
  • superoxide-generating NADPH oxidase activity
  • superoxide-generating NADPH oxidase activator activity
  • SH3 domain binding

Cellular Component

  • rough endoplasmic reticulum
  • Golgi apparatus
  • cytosol
  • plasma membrane
  • extrinsic component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000289473
Coding exons
11
Length
15351
Individuals with no LoFs
125412
Homozygous LoFs
0
Heterozygous LoFs
177
Defined
125589
p
0.000705
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.011131480.7650.000009122489
Missense (PolyPhen)3344.790.73676897
Synonymous0.9085564.30.8560.00000468731
Loss of Function1.21913.90.6496.79e-7239

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish0.0110.011notable
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000340.00033rare
South Asian0.0000650.000065rare
Other0.00200.0020notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). {ECO:0000269|PubMed:19801500, ECO:0000269|PubMed:2547247, ECO:0000269|PubMed:2550933}.;
Disease
DISEASE: Granulomatous disease, chronic, cytochrome-b-positive 1, autosomal recessive (CGD1) [MIM:233700]: A disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections. {ECO:0000269|PubMed:11133775, ECO:0000269|PubMed:23910690}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.384

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.764

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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