NCF4
Basic information
Region (hg38): 22:36860988-36878017
Links
Phenotypes
GenCC
Source:
- granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 (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, 3 | 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 | 19692703; 22157170; 22876374 |
ClinVar
This is a list of variants' phenotypes submitted to
- Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 (9 variants)
- Chronic granulomatous disease (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCF4 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 | 75 | 86 | ||||
missense | 139 | 148 | ||||
nonsense | 3 | |||||
start loss | 0 | |||||
frameshift | 8 | |||||
inframe indel | 3 | |||||
splice donor/acceptor (+/-2bp) | 5 | |||||
splice region | 7 | 13 | 20 | |||
non coding | 44 | 38 | 83 | |||
Total | 9 | 7 | 147 | 126 | 47 |
Highest pathogenic variant AF is 0.0000329
Variants in NCF4
This is a list of pathogenic ClinVar variants found in the NCF4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
22-36861077-C-T | Likely benign (May 20, 2019) | |||
22-36861135-G-A | Benign (Oct 24, 2018) | |||
22-36861189-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Mar 12, 2023) | ||
22-36861193-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (Jun 09, 2020) | ||
22-36861194-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (May 15, 2023) | ||
22-36861197-C-G | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (Aug 19, 2022) | ||
22-36861198-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Jan 26, 2024) | ||
22-36861199-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (Oct 17, 2022) | ||
22-36861201-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Nov 09, 2018) | ||
22-36861205-T-G | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Pathogenic (Jul 06, 2020) | ||
22-36861206-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (Aug 04, 2021) | ||
22-36861212-C-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Jul 07, 2020) | ||
22-36861213-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Nov 15, 2023) | ||
22-36861216-G-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Apr 10, 2023) | ||
22-36861223-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Aug 19, 2022) | ||
22-36862461-T-C | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Benign (Jan 02, 2024) | ||
22-36863879-C-T | Benign (Sep 26, 2018) | |||
22-36864038-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Feb 13, 2023) | ||
22-36864039-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Conflicting classifications of pathogenicity (Jan 08, 2024) | ||
22-36864039-G-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Aug 30, 2019) | ||
22-36864042-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (Jan 26, 2022) | ||
22-36864044-G-A | Chronic granulomatous disease | Likely pathogenic (Jul 19, 2021) | ||
22-36864053-A-G | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Uncertain significance (May 06, 2022) | ||
22-36864062-C-T | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 • not specified | Uncertain significance (Jun 01, 2024) | ||
22-36864063-G-A | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | Likely benign (Jan 25, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
NCF4 | protein_coding | protein_coding | ENST00000397147 | 8 | 17028 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
9.02e-8 | 0.519 | 125613 | 1 | 134 | 125748 | 0.000537 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.227 | 215 | 206 | 1.04 | 0.0000143 | 2247 |
Missense in Polyphen | 61 | 60.58 | 1.0069 | 621 | ||
Synonymous | -1.41 | 100 | 83.6 | 1.20 | 0.00000560 | 710 |
Loss of Function | 0.949 | 13 | 17.3 | 0.754 | 8.54e-7 | 193 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000276 | 0.000275 |
Ashkenazi Jewish | 0.000694 | 0.000695 |
East Asian | 0.000218 | 0.000217 |
Finnish | 0.0000462 | 0.0000462 |
European (Non-Finnish) | 0.000756 | 0.000747 |
Middle Eastern | 0.000218 | 0.000217 |
South Asian | 0.000915 | 0.000915 |
Other | 0.000815 | 0.000815 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex. {ECO:0000269|PubMed:8280052}.;
- Disease
- DISEASE: Granulomatous disease, chronic, cytochrome-b-positive 3, autosomal recessive (CGD3) [MIM:613960]: 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:19692703}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Phagosome - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Leishmaniasis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Microglia Pathogen Phagocytosis Pathway;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;Signaling by Receptor Tyrosine Kinases
(Consensus)
Intolerance Scores
- loftool
- 0.855
- rvis_EVS
- -0.78
- rvis_percentile_EVS
- 12.97
Haploinsufficiency Scores
- pHI
- 0.116
- hipred
- N
- hipred_score
- 0.144
- ghis
- 0.572
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.806
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ncf4
- Phenotype
- immune system phenotype; 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); homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- superoxide metabolic process;phagocytosis;immune response;positive regulation of catalytic activity;respiratory burst;vascular endothelial growth factor receptor signaling pathway;oxidation-reduction process
- Cellular component
- cytosol;endosome membrane;membrane;phagolysosome;NADPH oxidase complex
- Molecular function
- protein binding;superoxide-generating NADPH oxidase activator activity;phosphatidylinositol-3-phosphate binding;phosphatidylinositol binding;protein dimerization activity