NCF2 (neutrophil cytosolic factor 2)

Gene

• Entrez ID: 4688
• Gene name: Neutrophil cytosolic factor 2
• Gene symbol: NCF2
• Synonyms: NCF-2, NOXA2, P67-PHOX, P67PHOX
• Chromosome: 1
• Chromosome location: 1q25.3
• Summary: This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome.

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs115365142	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Missense variant, intron variant, coding sequence variant
rs119103274	G>A	Pathogenic	Missense variant, intron variant, coding sequence variant
rs119103275	C>T	Pathogenic	Missense variant, coding sequence variant
rs119103276	G>A,C,T	Pathogenic, benign	Stop gained, missense variant, coding sequence variant
rs137854508	G>A	Likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs137878529	T>C,G	Pathogenic	Missense variant, intron variant, coding sequence variant
rs143889676	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs147415774	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs267606912	T>A	Pathogenic	Intron variant, missense variant, coding sequence variant
rs374402066	G>A	Pathogenic	Coding sequence variant, stop gained
rs755796920	G>A,T	Pathogenic	Missense variant, intron variant, coding sequence variant, stop gained
rs766745748	G>A	Likely-pathogenic	Stop gained, intron variant, coding sequence variant
rs777621636	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs796065030	->CT	Pathogenic	Coding sequence variant, intron variant, frameshift variant
rs796065031	CTTAG>-	Pathogenic	Coding sequence variant, frameshift variant
rs796065032	C>G,T	Pathogenic	Splice donor variant
rs796065033	TTCTTGTCC>-	Pathogenic, likely-pathogenic	Coding sequence variant, inframe deletion
rs990043411	C>T	Pathogenic	Splice donor variant
rs1064794299	TG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1290169467	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1472146831	TCCTT>-	Pathogenic	Coding sequence variant, stop gained
rs1558092897	C>G	Likely-pathogenic	Splice donor variant
rs1558098982	T>-	Pathogenic	Intron variant, coding sequence variant, frameshift variant
rs1572151178	G>A	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022884	hsa-miR-124-3p	Microarray	18668037
MIRT2578685	hsa-miR-136	CLIP-seq
MIRT2578686	hsa-miR-3622a-3p	CLIP-seq
MIRT2578687	hsa-miR-3622b-3p	CLIP-seq
MIRT2578688	hsa-miR-4691-5p	CLIP-seq
MIRT2578689	hsa-miR-4764-3p	CLIP-seq
MIRT2578685	hsa-miR-136	CLIP-seq
MIRT2578686	hsa-miR-3622a-3p	CLIP-seq
MIRT2578687	hsa-miR-3622b-3p	CLIP-seq
MIRT2578688	hsa-miR-4691-5p	CLIP-seq
MIRT2578689	hsa-miR-4764-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
IRF1	Activation	10570299
IRF8	Activation	10570299
MED15	Unknown	20025940
PLAGL2	Activation	17462995;20025940
SPI1	Activation	10570299
SPI1	Unknown	20025940

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001669	Component	Acrosomal vesicle	IEA
GO:0002479	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS
GO:0005515	Function	Protein binding	IPI	7938008, 8280052, 11483497, 11733522, 12887891, 15591124, 15657040, 16297854, 16782902, 19129478, 21516116, 22203994, 25416956, 25910212, 26871637, 31515488, 32296183
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	IDA	8280052
GO:0005829	Component	Cytosol	TAS
GO:0006801	Process	Superoxide metabolic process	TAS	7938008
GO:0006909	Process	Phagocytosis	IEA
GO:0006968	Process	Cellular defense response	TAS	1692159
GO:0008022	Function	Protein C-terminus binding	IPI	9365277
GO:0009055	Function	Electron transfer activity	TAS	1692159
GO:0016020	Component	Membrane	IDA	8280052
GO:0016175	Function	Superoxide-generating NAD(P)H oxidase activity	IGI	8280052
GO:0016176	Function	Superoxide-generating NADPH oxidase activator activity	IBA	21873635
GO:0022900	Process	Electron transport chain	IEA
GO:0032010	Component	Phagolysosome	TAS
GO:0034599	Process	Cellular response to oxidative stress	TAS
GO:0042554	Process	Superoxide anion generation	IBA	21873635
GO:0042554	Process	Superoxide anion generation	TAS	7938008
GO:0043020	Component	NADPH oxidase complex	IDA	8280052
GO:0043020	Component	NADPH oxidase complex	TAS	7938008
GO:0045087	Process	Innate immune response	TAS	7938008
GO:0045454	Process	Cell redox homeostasis	TAS
GO:0045730	Process	Respiratory burst	TAS	7938008
GO:0048010	Process	Vascular endothelial growth factor receptor signaling pathway	TAS
GO:0050790	Process	Regulation of catalytic activity	IEA

Other IDs

• MIM: 608515
• HGNC: 7661
• e!Ensembl: ENSG00000116701

Protein

• UniProt ID: P19878
• Protein name: Neutrophil cytosol factor 2 (NCF-2) (67 kDa neutrophil oxidase factor) (NADPH oxidase activator 2) (Neutrophil NADPH oxidase factor 2) (p67-phox)
• Protein function: Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:12207919, PubMed:38355798). In the activated complex, electrons are first transferr
• PDB: 1E96, 1HH8, 1K4U, 1OEY, 1WM5, 2DMO, 8WEJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13181	TPR_8	37 → 69	Tetratricopeptide repeat	Repeat
  PF00018	SH3_1	246 → 291	SH3 domain	Domain
  PF00564	PB1	351 → 429	PB1 domain	Domain
  PF00018	SH3_1	463 → 508	SH3 domain	Domain

• Sequence:

  MSLVEAISLWNEGVLAADKKDWKGALDAFSAVQDPHSRICFNIGCMYTILKNMTEAEKAF
  TRSINRDKHLAVAYFQRGMLYYQTEKYDLAIKDLKEALIQLRGNQLIDYKILGLQFKLFA
  CEVLYNIAFMYAKKEEWKKAEEQLALATSMKSEPRHSKIDKAMECVWKQKLYEPVVIPVG
  KLFRPNERQVAQLAKKDYLGKATVVASVVDQDSFSGFAPLQPQAAEPPPRPKTPEIFRAL
  EGEAHRVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLEPVELR
  IHPQQQPQEESSPQSDIPAPPSSKAPGRPQLSPGQKQKEEPKEVKLSVPMPYTLKVHYKY
  TVVMKTQPGLPYSQVRDMVSKKLELRLEHTKLSYRPRDSNELVPLSEDSMKDAWGQVKNY
  CLTLWCENTVGDQGFPDEPKESEKADANNQTTEPQLKKGSQVEALFSYEATQPEDLEFQE
  GDIILVLSKVNEEWLEGECKGKVGIFPKVFVEDCATTDLESTRREV

• Sequence length: 526

Pathways

KEGG:

Phagosome
Osteoclast differentiation
Neutrophil extracellular trap formation
Leukocyte transendothelial migration
Prion disease
Leishmaniasis
Chemical carcinogenesis - reactive oxygen species
Diabetic cardiomyopathy
Lipid and atherosclerosis
Fluid shear stress and atherosclerosis

Reactome:

ROS and RNS production in phagocytes
Cross-presentation of particulate exogenous antigens (phagosomes)
Detoxification of Reactive Oxygen Species
VEGFA-VEGFR2 Pathway
RHO GTPases Activate NADPH Oxidases

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Chronic obstructive pulmonary disease	Chronic Obstructive Airway Disease	rs2227956, rs1008438, rs1043618, rs562047, rs1061581, rs2763979, rs6457452, rs13147758, rs1828591, rs13118928
Granulomatous disease	Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Positive, Type II, Chronic granulomatous disease	rs796065030, rs374402066, rs796065031, rs796065032, rs119103276, rs796065033, rs119103274, rs4029402, rs1563003964, rs119103270, rs1307080411, rs119103271, rs119103272, rs119103273, rs104894513, rs104894514, rs104894515, rs1567609091, rs104894511, rs28941476, rs1907271302, rs119103269, rs137854585, rs137854588, rs137854590, rs137854591, rs137854596, rs2146821097, rs137854592, rs1602175016, rs137854593, rs137854594, rs387906485, rs2146810847, rs1569478551, rs387906486, rs151344498, rs151344497, rs876657377, rs387906808, rs193922445, rs193922446, rs193922448, rs193922449, rs179363892, rs179363894, rs151344484, rs151344470, rs151344473, rs151344454, rs151344481, rs151344491, rs151344482, rs151344462, rs151344466, rs151344467, rs137854508, rs193922450, rs869025585, rs886039335, rs886039337, rs886041194, rs886041192, rs990043411, rs1057517730, rs1064794299, rs1453468510, rs28445840, rs145360423, rs1131691828, rs1556473078, rs1556464554, rs1556470775, rs1556464116, rs1556473119, rs1556469197, rs1556471620, rs1558098982, rs1290169467, rs1558092897, rs777621636, rs1569479943, rs1569480333, rs1567608830, rs1567608853, rs1439134665, rs1569480031, rs1569479953, rs766745748, rs782800778, rs1584370623, rs779809359, rs1472146831, rs1572151178, rs1352931329, rs1597374562, rs1602183698, rs200129367, rs1602186299, rs771926427, rs1602173465, rs1200078508, rs1602184316, rs1602183244, rs535897564, rs151344455, rs180899069, rs1929244686, rs1929497736, rs1929531349, rs1352107832, rs1929527785, rs1929245964, rs1939893821, rs763678131	8286749, 20167518, 23910690, 18625437, 10498624, 10598813, 19624736, 9070911, 25937994, 11112388, 16937026
Osteomyelitis	Osteomyelitis	rs11125529, rs10936599, rs7675998, rs398652, rs755017
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963, rs2240340, rs1557787212	12833524, 26546613, 30573655

Unknown
Disease name	Disease term	dbSNP ID	References
Celiac disease	Celiac Disease	rs2305764, rs35218876	26546613
Eczema	Eczema
Gingivitis	Gingivitis
Granulomatosis	Granulomatosis
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes
Inflammatory abnormality of the eye	Inflammatory abnormality of the eye
Lupus erythematosus	Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic		27399966, 28714469, 30573655, 26606652, 26502338, 19838195
Lymphadenitis	Lymphadenitis
Malabsorption syndrome	Malabsorption Syndrome
Mediastinal lymphadenopathy	Mediastinal lymphadenopathy
Myositis	Myositis		30573655
Otitis media	Otitis Media	rs601338, rs1047781, rs1800028
Scleroderma	Systemic Scleroderma		30573655
Sinusitis	Sinusitis