NCF1
neutrophil cytosolic factor 1
Basic information
Region (hg38): 7:74774011-74789315
Links
Phenotypes
GenCC
Source:
- granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 (Strong), mode of inheritance: AR
- chronic granulomatous disease (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Granulomatous disease, chronic, autosomal recessive, 1 | AR | Allergy/Immunology/Infectious | 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 | Allergy/Immunology/Infectious | 5755008; 6848934; 3011845; 3339133; 2770793; 2011585; 11060536; 10706888; 11133775; 16972229; 19329991; 22157170; 22876374; 22924696 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (4 variants)
- Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 (3 variants)
- Granulomatous disease, chronic, X-linked (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCF1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 12 | 16 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 3 | 1 | 4 | |||
| non coding | 6 | |||||
| Total | 4 | 2 | 13 | 5 | 7 |
Highest pathogenic variant AF is 0.000854
Variants in NCF1
This is a list of pathogenic ClinVar variants found in the NCF1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-74777264-C-A | Uncertain significance (Apr 06, 2017) | |||
| 7-74777266-GGT-G | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 • Granulomatous disease, chronic, X-linked | Pathogenic (Dec 18, 2024) | ||
| 7-74777302-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Uncertain significance (Mar 30, 2021) | ||
| 7-74777318-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Pathogenic (Mar 02, 2018) | ||
| 7-74777319-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Pathogenic (Aug 16, 2023) | ||
| 7-74777361-T-C | not specified | Benign (Jan 24, 2024) | ||
| 7-74777361-T-T | not specified | Benign (Mar 28, 2016) | ||
| 7-74777383-C-T | Benign (Mar 03, 2015) | |||
| 7-74777420-G-C | Benign (Mar 03, 2015) | |||
| 7-74777454-C-T | Benign (Mar 03, 2015) | |||
| 7-74777567-C-T | Likely benign (Feb 24, 2021) | |||
| 7-74779113-C-CA | Pathogenic (Jun 15, 2016) | |||
| 7-74779119-C-T | Inborn genetic diseases | Uncertain significance (Jul 14, 2024) | ||
| 7-74779135-C-T | Likely benign (Apr 01, 2023) | |||
| 7-74779148-C-T | Inborn genetic diseases | Uncertain significance (Feb 23, 2023) | ||
| 7-74779274-G-A | Benign (May 01, 2024) | |||
| 7-74779289-G-A | Inborn genetic diseases | Uncertain significance (Feb 12, 2024) | ||
| 7-74779296-G-A | Granulomatous disease, chronic, X-linked • Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Uncertain significance (Apr 26, 2022) | ||
| 7-74779298-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Pathogenic (Dec 01, 2006) | ||
| 7-74779311-C-CCGAG | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Likely pathogenic (Sep 22, 2024) | ||
| 7-74779319-T-G | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 | Conflicting classifications of pathogenicity (Aug 01, 2023) | ||
| 7-74779322-A-G | Benign (Dec 23, 2023) | |||
| 7-74779322-A-A | not specified | Benign (Jan 17, 2024) | ||
| 7-74779331-A-G | Inborn genetic diseases | Uncertain significance (Dec 21, 2023) | ||
| 7-74779336-C-A | Inborn genetic diseases | Uncertain significance (Jun 16, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NCF1 | protein_coding | protein_coding | ENST00000289473 | 11 | 15351 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000283 | 0.792 | 125412 | 0 | 177 | 125589 | 0.000705 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.01 | 113 | 148 | 0.765 | 0.00000912 | 2489 |
| Missense in Polyphen | 33 | 44.79 | 0.73676 | 897 | ||
| Synonymous | 0.908 | 55 | 64.3 | 0.856 | 0.00000468 | 731 |
| Loss of Function | 1.21 | 9 | 13.9 | 0.649 | 6.79e-7 | 239 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000290 | 0.000290 |
| Ashkenazi Jewish | 0.0115 | 0.0115 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000337 | 0.000335 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000655 | 0.0000653 |
| Other | 0.00196 | 0.00196 |
dbNSFP
Source:
- 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.;
- Pathway
- 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);Osteoclast differentiation - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);AGE-RAGE pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Microglia Pathogen Phagocytosis Pathway;RAGE;Signal Transduction;Detoxification of Reactive Oxygen Species;VEGFA-VEGFR2 Pathway;Cellular responses to stress;ROS, RNS production in phagocytes;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Cellular responses to external stimuli;RHO GTPases Activate NADPH Oxidases;RHO GTPase Effectors;Signaling by Rho GTPases;Cross-presentation of particulate exogenous antigens (phagosomes);Signaling by VEGF;TNFalpha;Signaling by Receptor Tyrosine Kinases;RAC1 signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.384
Haploinsufficiency Scores
- pHI
- 0.568
- hipred
- Y
- hipred_score
- 0.801
- ghis
- 0.516
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.764
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ncf1
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype;
Zebrafish Information Network
- Gene name
- ncf1
- Affected structure
- respiratory burst
- Phenotype tag
- abnormal
- Phenotype quality
- decreased process quality
Gene ontology
- Biological process
- protein targeting to membrane;superoxide metabolic process;apoptotic process;cellular defense response;positive regulation of phosphatidylinositol 3-kinase signaling;electron transport chain;cellular response to reactive oxygen species;superoxide anion generation;innate immune response;respiratory burst;positive regulation of epidermal growth factor-activated receptor activity;positive regulation of transcription, DNA-templated;positive regulation of JNK cascade;vascular endothelial growth factor receptor signaling pathway;cellular response to cadmium ion;positive regulation of p38MAPK cascade
- Cellular component
- rough endoplasmic reticulum;Golgi apparatus;cytosol;plasma membrane;extrinsic component of membrane;dendrite;phagolysosome;NADPH oxidase complex;neuronal cell body
- Molecular function
- protein binding;electron transfer activity;superoxide-generating NADPH oxidase activity;superoxide-generating NADPH oxidase activator activity;SH3 domain binding;phosphatidylinositol binding;phosphatidylinositol-3,4-bisphosphate binding