NCF4 (neutrophil cytosolic factor 4)

Gene

• Entrez ID: 4689
• Gene name: Neutrophil cytosolic factor 4
• Gene symbol: NCF4
• Synonyms: CGD3, NCF, P40PHOX, SH3PXD4
• Chromosome: 22
• Chromosome location: 22q12.3
• Summary: The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It i

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs201021542	C>T	Pathogenic	Coding sequence variant, stop gained, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017337	hsa-miR-335-5p	Microarray	18185580
MIRT1176354	hsa-miR-3160-3p	CLIP-seq
MIRT1176355	hsa-miR-3921	CLIP-seq
MIRT1176356	hsa-miR-4251	CLIP-seq
MIRT1176357	hsa-miR-4279	CLIP-seq
MIRT1176358	hsa-miR-4329	CLIP-seq
MIRT1176359	hsa-miR-4653-5p	CLIP-seq
MIRT1176360	hsa-miR-493	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002479	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS
GO:0005515	Function	Protein binding	IPI	8280052, 9365277, 11483497, 12887891, 15657040, 16297854, 16782902
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	IDA	8280052
GO:0005829	Component	Cytosol	TAS
GO:0006801	Process	Superoxide metabolic process	IBA	21873635
GO:0006909	Process	Phagocytosis	IEA
GO:0010008	Component	Endosome membrane	IDA	11684018
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:0016176	Function	Superoxide-generating NADPH oxidase activator activity	IMP	8280052
GO:0032010	Component	Phagolysosome	TAS
GO:0032266	Function	Phosphatidylinositol-3-phosphate binding	IDA	11684018
GO:0034599	Process	Cellular response to oxidative stress	TAS
GO:0043020	Component	NADPH oxidase complex	IBA	21873635
GO:0043020	Component	NADPH oxidase complex	IDA	8280052
GO:0045454	Process	Cell redox homeostasis	TAS
GO:0045730	Process	Respiratory burst	IEA
GO:0048010	Process	Vascular endothelial growth factor receptor signaling pathway	TAS
GO:0050790	Process	Regulation of catalytic activity	IEA
GO:0060090	Function	Molecular adaptor activity	IBA	21873635

Other IDs

• MIM: 601488
• HGNC: 7662
• e!Ensembl: ENSG00000100365

Protein

• UniProt ID: Q15080
• Protein name: Neutrophil cytosol factor 4 (NCF-4) (Neutrophil NADPH oxidase factor 4) (SH3 and PX domain-containing protein 4) (p40-phox) (p40phox)
• 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(-)) (Probable). In the activated complex, electrons are first transferred from NADPH to flavin
• PDB: 1H6H, 1OEY, 1W6X, 1W70, 1Z9Q, 2DYB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00787	PX	45 → 136	PX domain	Domain
  PF00018	SH3_1	176 → 221	SH3 domain	Domain
  PF00564	PB1	237 → 329	PB1 domain	Domain

• Sequence:

  MAVAQQLRAESDFEQLPDDVAISANIADIEEKRGFTSHFVFVIEVKTKGGSKYLIYRRYR
  QFHALQSKLEERFGPDSKSSALACTLPTLPAKVYVGVKQEIAEMRIPALNAYMKSLLSLP
  VWVLMDEDVRIFFYQSPYDSEQVPQALRRLRPRTRKVKSVSPQGNSVDRMAAPRAEALFD
  FTGNSKLELNFKAGDVIFLLSRINKDWLEGTVRGATGIFPLSFVKILKDFPEEDDPTNWL
  RCYYYEDTISTIKDIAVEEDLSSTPLLKDLLELTRREFQREDIALNYRDAEGDLVRLLSD
  EDVALMVRQARGLPSQKRLFPWKLHITQKDNYRVYNTMP

• Sequence length: 339

Pathways

KEGG:

Phagosome
Osteoclast differentiation
Neutrophil extracellular trap formation
Leukocyte transendothelial migration
Prion disease
Leishmaniasis
Diabetic cardiomyopathy
Lipid 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	Chronic granulomatous disease, GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, CYTOCHROME b-POSITIVE, TYPE III	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	19692703, 17435756, 19692703, 29969437

Unknown
Disease name	Disease term	dbSNP ID	References
Aphthous ulcer	Recurrent aphthous ulcer
Colitis	Colitis
Crohn disease	Crohn Disease, Regional enteritis, NON RARE IN EUROPE: Crohn disease	rs2066847, rs2066844, rs886052047, rs5743265, rs111608429, rs104895438	28067908, 17435756, 17435756
Crohn`s disease of large bowel	Crohn`s disease of large bowel		17435756
Crohn`s disease of the ileum	Crohn`s disease of the ileum		17435756
Eczema	Eczema
Gingivitis	Gingivitis
Heart diseases	Heart Diseases		16330681
Ileocolitis	IIeocolitis		17435756
Inflammatory abnormality of the eye	Inflammatory abnormality of the eye
Malabsorption syndrome	Malabsorption Syndrome
Mediastinal lymphadenopathy	Mediastinal lymphadenopathy
Otitis media	Otitis Media	rs601338, rs1047781, rs1800028
Perioral eczema	Perioral eczema
Sinusitis	Sinusitis, Recurrent sinusitis