NCF4

neutrophil cytosolic factor 4

Basic information

Region (hg38): 22:36860988-36878017

Links

ENSG00000100365 ∙ NCBI:4689 ∙ OMIM:601488 ∙ HGNC:7662 ∙ Uniprot:Q15080 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the NCF4 gene.

• Granulomatous_disease,_chronic,_autosomal_recessive,_cytochrome_b-positive,_type_3 (332 variants)
• not_specified (67 variants)
• not_provided (41 variants)
• NCF4-related_disorder (12 variants)
• Chronic_granulomatous_disease (6 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. These statistics are base on transcript: NM_000000631.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	68	6	77
missense	1		112	11		124
nonsense	2		1			3
start loss		1				1
frameshift	5	2				7
splice donor/acceptor (+/-2bp)	1	7	2			10
Total	9	10	118	79	6

Highest pathogenic variant AF is 0.00016110323

GnomAD

Source: gnomAD

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: dbNSFP

• 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