NCF2

neutrophil cytosolic factor 2, the group of Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 1:183554460-183590905

Links

ENSG00000116701 ∙ NCBI:4688 ∙ OMIM:608515 ∙ HGNC:7661 ∙ Uniprot:P19878 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chronic granulomatous disease (Supportive), mode of inheritance: AR
• granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (Definitive), mode of inheritance: AR
• granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Granulomatous disease, chronic, autosomal recessive, 2	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	2770793; 7795241; 10498624; 11060536; 22157170; 22876374; 23264412

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCF2 gene.

• Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (402 variants)
• not provided (87 variants)
• Chronic granulomatous disease (15 variants)
• not specified (15 variants)
• Inborn genetic diseases (14 variants)
• NCF2-related condition (2 variants)
• - (2 variants)
• Developmental and epileptic encephalopathy, 28 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCF2 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			4	73	2	79
missense		1	132	7	3	143
nonsense	13	3				16
start loss	1					1
frameshift	14	3	3			20
inframe indel	1		3			4
splice donor/acceptor (+/-2bp)	4	8	1	1		14
splice region			13	29		42
non coding			14	69	37	120
Total	33	15	157	150	42

Highest pathogenic variant AF is 0.0000197

Variants in NCF2

This is a list of pathogenic ClinVar variants found in the NCF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-183555571-AAAAC-A		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555600-T-TA		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555605-G-GTAACC		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555608-A-T		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555673-T-G		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555720-C-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Benign (Jan 13, 2018)
1-183555720-C-CTGA		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555724-GT-G		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555724-G-GT		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555843-G-GGAA			Likely benign (Nov 16, 2018)
1-183555848-ACT-A		Chronic granulomatous disease	Uncertain significance (Jun 14, 2016)
1-183555856-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Jan 13, 2018)
1-183556021-T-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Jan 12, 2018)
1-183556118-C-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Aug 31, 2021)
1-183556118-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Likely benign (Mar 21, 2023)
1-183556121-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Likely benign (Jan 21, 2024)
1-183556123-C-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Oct 05, 2023)
1-183556125-TCTCTC-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Jul 31, 2022)
1-183556131-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Aug 10, 2022)
1-183556132-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 • Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
1-183556144-A-C		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Aug 27, 2021)
1-183556145-A-C		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Aug 11, 2021)
1-183556147-C-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Likely benign (Jan 30, 2024)
1-183556149-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Jun 13, 2022)
1-183556153-T-C		Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Uncertain significance (Oct 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCF2	protein_coding	protein_coding	ENST00000367535	15	35314

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.01e-7	0.998	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	225	273	0.823	0.0000149	3457
Missense in Polyphen		73	91.443	0.79831		1141
Synonymous	-0.0865	107	106	1.01	0.00000585	973
Loss of Function	2.71	16	32.7	0.489	0.00000177	380

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000781	0.000781
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000211	0.000211
Middle Eastern	0.000217	0.000217
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

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:12207919}.
• Disease: DISEASE: Granulomatous disease, chronic, cytochrome-b-positive 2, autosomal recessive (CGD2) [MIM:233710]: 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:10498624, ECO:0000269|PubMed:10598813, ECO:0000269|PubMed:11112388, ECO:0000269|PubMed:16937026, ECO:0000269|PubMed:18625437, ECO:0000269|PubMed:19624736, ECO:0000269|PubMed:20167518, ECO:0000269|PubMed:23910690, ECO:0000269|PubMed:8286749, ECO:0000269|PubMed:9070911}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phagosome - 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);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;VEGFA-VEGFR2 Signaling Pathway;Microglia Pathogen Phagocytosis Pathway;TYROBP Causal Network;Signal Transduction;Detoxification of Reactive Oxygen Species;VEGFA-VEGFR2 Pathway;rho cell motility signaling pathway;t cell receptor signaling pathway;rac1 cell motility signaling 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;adp-ribosylation factor;Cellular responses to external stimuli;RHO GTPases Activate NADPH Oxidases;RHO GTPase Effectors;Signaling by Rho GTPases;fmlp induced chemokine gene expression in hmc-1 cells;Cross-presentation of particulate exogenous antigens (phagosomes);Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;RAC1 signaling pathway (Consensus)

Recessive Scores

• pRec: 0.324

Intolerance Scores

• loftool: 0.912
• rvis_EVS: 1.31
• rvis_percentile_EVS: 94.01

Haploinsufficiency Scores

• pHI: 0.116
• hipred: Y
• hipred_score: 0.706
• ghis: 0.439

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.590

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Ncf2
• Phenotype: cellular phenotype; homeostasis/metabolism 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); hematopoietic system phenotype; respiratory system phenotype; immune system phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: superoxide metabolic process;phagocytosis;cellular defense response;electron transport chain;superoxide anion generation;positive regulation of catalytic activity;innate immune response;respiratory burst;vascular endothelial growth factor receptor signaling pathway
• Cellular component: acrosomal vesicle;nucleolus;cytosol;phagolysosome;NADPH oxidase complex
• Molecular function: protein binding;protein C-terminus binding;electron transfer activity;superoxide-generating NADPH oxidase activity;superoxide-generating NADPH oxidase activator activity;Rac GTPase binding