NCF2 (neutrophil cytosolic factor 2)

Gene

• Entrez ID: 4688
• Gene name: Neutrophil cytosolic factor 2
• Gene symbol: NCF2
• Synonyms (NCBI Gene): 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:0005515	Function	Protein binding	IPI	7938008, 8280052, 9365277, 11483497, 11733522, 12887891, 15591124, 15657040, 16297854, 16782902, 19129478, 21516116, 22203994, 25416956, 25910212, 26871637, 31515488, 32296183
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA	8280052
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	NAS	27048830
GO:0006801	Process	Superoxide metabolic process	TAS	7938008
GO:0006909	Process	Phagocytosis	IEA
GO:0006968	Process	Cellular defense response	TAS	1692159
GO:0009055	Function	Electron transfer activity	TAS	1692159
GO:0016020	Component	Membrane	IDA	8280052
GO:0016175	Function	Superoxide-generating NAD(P)H oxidase activity	IEA
GO:0016176	Function	Superoxide-generating NADPH oxidase activator activity	IBA
GO:0016176	Function	Superoxide-generating NADPH oxidase activator activity	IEA
GO:0016176	Function	Superoxide-generating NADPH oxidase activator activity	IMP	8280052
GO:0031267	Function	Small GTPase binding	IEA
GO:0032010	Component	Phagolysosome	TAS
GO:0042554	Process	Superoxide anion generation	IBA
GO:0042554	Process	Superoxide anion generation	IDA	38355798
GO:0042554	Process	Superoxide anion generation	IEA
GO:0042554	Process	Superoxide anion generation	IMP	8280052
GO:0042554	Process	Superoxide anion generation	TAS	7938008
GO:0043020	Component	NADPH oxidase complex	IDA	8280052, 38355798
GO:0043020	Component	NADPH oxidase complex	IEA
GO:0043020	Component	NADPH oxidase complex	NAS	24598074
GO:0043020	Component	NADPH oxidase complex	TAS	7938008
GO:0045087	Process	Innate immune response	TAS	7938008
GO:0045730	Process	Respiratory burst	IEA
GO:0045730	Process	Respiratory burst	NAS	27048830
GO:0045730	Process	Respiratory burst	TAS	7938008

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
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Chronic granulomatous disease	Likely pathogenic; Pathogenic	rs2102875639, rs2527964515, rs2527963676, rs2527910800, rs752901695, rs749606885, rs2527946248, rs137854508	RCV002223034 RCV003155833 RCV003226674 RCV003331828 RCV005240820 RCV004701817 RCV003988500 RCV004586536
Colon adenocarcinoma	Pathogenic	rs763317358	RCV005922455
Colorectal cancer	Likely pathogenic; Pathogenic	rs137854508	RCV005890408
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	Likely pathogenic; Pathogenic	rs759285400, rs774932046, rs763317358, rs2102898304, rs2102887348, rs2102934288, rs2102942512, rs2102903043, rs2102934597, rs1349405769, rs2102890652, rs796065030, rs374402066, rs796065031, rs796065032, rs119103276, rs796065033, rs119103274, rs2527930575, rs764314608, rs2528039666, rs2527964515, rs2527963676, rs2527910800, rs1672642650, rs2528040305, rs756393096, rs2527911236, rs2527964072, rs752901695, rs2527911315, rs2528021760, rs898012170, rs2527976811, rs1672328940, rs2527930725, rs2528021632, rs749606885, rs771126735, rs2527964759, rs990043411, rs1064794299, rs1558098982, rs1290169467, rs1558092897, rs777621636, rs766745748, rs1472146831, rs1572151178, rs137854508, rs1352107832, rs750782115	RCV001378719 RCV001390471 RCV001784717 RCV001978022 RCV001966085 RCV001987692 RCV001909878 RCV002043024 RCV001972801 RCV001888511 RCV001914597 RCV000002327 RCV000002329 RCV000002330 RCV000002331 RCV000002332 RCV000002333 RCV000002334 RCV002664194 RCV002648228 RCV002671990 RCV003497976 RCV003603153 RCV003497992 RCV003498252 RCV003498798 RCV003498140 RCV003499910 RCV003499911 RCV003499912 RCV003499379 RCV003499427 RCV003603318 RCV003603385 RCV003604740 RCV003604981 RCV003605052 RCV003603767 RCV003881640 RCV003989907 RCV001861411 RCV001865445 RCV000690026 RCV000695278 RCV000694265 RCV000702612 RCV002535792 RCV000814529 RCV000816923 RCV000059369 RCV001065930 RCV002558732
NCF2-related disorder	Likely pathogenic	rs1672324636	RCV003403065

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
-	no classification for the single variant	rs267606912, rs137878529	-
Acute myeloid leukemia	Benign	rs789191, rs36113295, rs2274065	RCV005917130 RCV005891279 RCV005891542
Cervical cancer	Benign	rs36113295	RCV005891281
Cholangiocarcinoma	Benign	rs2274065	RCV005891546
Clear cell carcinoma of kidney	Benign	rs36113295	RCV005891282
Developmental and epileptic encephalopathy, 28	Benign; Likely benign	rs35012521	RCV001258235
Familial pancreatic carcinoma	Benign	rs36113295	RCV005891284
Gastric cancer	Benign	rs36113295	RCV005891285
Lung cancer	Benign	rs36113295	RCV005891289
Lymphoma	Benign	rs36113295	RCV005891286
Malignant lymphoma, large B-cell, diffuse	Benign	rs789191	RCV005917132
Malignant tumor of esophagus	Benign	rs789191, rs36113295, rs2274065	RCV005917131 RCV005891280 RCV005891543
Ovarian serous cystadenocarcinoma	Benign	rs36113295	RCV005891287
Sarcoma	Benign	rs789191	RCV005917133
Thymoma	Benign	rs36113295, rs2274065	RCV005891288 RCV005891545
Uterine carcinosarcoma	Benign	rs789191, rs2274065	RCV005917134 RCV005891544
Uterine corpus endometrial carcinoma	Benign	rs36113295	RCV005891290
Uveal melanoma	Benign	rs36113295	RCV005891283

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Associate	27540973
Anal Gland Neoplasms	Associate	29454792
Aneurysm Ruptured	Associate	33174039
Arthritis Rheumatoid	Associate	17897462, 33145364
Atherosclerosis	Associate	34122426, 34925641
Atrial Fibrillation	Associate	35790963, 36863715
Autoimmune Diseases	Associate	34708124, 34971477
Carcinogenesis	Associate	21119665
Carcinoma Hepatocellular	Associate	36680322, 38287833
Carcinoma Non Small Cell Lung	Associate	33651148
Carcinoma Renal Cell	Associate	21944129, 34528699, 34708124
Colitis Ulcerative	Stimulate	39647286
Colonic Neoplasms	Associate	27540973
Congenital heart block	Associate	28626076
Coronary Artery Disease	Associate	31245869
Coronary Restenosis	Associate	35144391
Crohn Disease	Associate	29454792
Death	Stimulate	21944129
Diabetic Nephropathies	Associate	37038746
Dystonic Disorders	Associate	19279361
Friedreich Ataxia	Associate	27078885
Gaucher Disease	Inhibit	28011901
Gaucher Disease	Associate	28011901
Genetic Diseases Inborn	Associate	10498624, 7903171
Glioma	Associate	19423540
Granulomatous Disease Chronic	Associate	10233905, 10498624, 10627478, 10706888, 11262407, 1332032, 19953534, 22514628, 22924696, 23264412, 23306776, 29073922, 30506560, 33717137, 33746979, 34971477, 7795241, 7803798, 7903171, 8280052, 8286749, 8639802, 8781442, 8879195, 9057660, 9129047
Granulomatous Disease Chronic	Inhibit	33717137, 7803798, 8182143, 8286749
Granulomatous Disease Chronic Autosomal Recessive Cytochrome B Positive Type II	Inhibit	10498624
Granulomatous Disease Chronic Autosomal Recessive Cytochrome B Positive Type II	Associate	10498624, 19953534
Heart Failure	Stimulate	18387435
Hyperlipidemias	Stimulate	31245869
Hypertension	Associate	29463833
Immunologic Deficiency Syndromes	Stimulate	23306776
Inflammation	Associate	21944129, 28011901, 37038746
Inflammation	Stimulate	28626076
Inflammatory Bowel Diseases	Associate	21900546, 39273699
Intracranial Aneurysm	Associate	33174039
Lung Diseases	Associate	22514628
Lupus Erythematosus Systemic	Associate	22046141, 22203994, 23740754, 24163247, 25795782, 26606652, 29070082, 34971477, 38442270
Metabolic Diseases	Associate	22904171
Metabolic Syndrome	Associate	31796056
MINOCA	Associate	31245869
Multiple Myeloma	Stimulate	37775746
Myocardial Infarction	Associate	34490057
Myopathy Central Core	Associate	36035208
Neoplasm Metastasis	Associate	34708124
Neoplasms	Associate	21119665, 34708124
Neoplasms	Inhibit	34971930
Neoplasms Squamous Cell	Associate	21119665
Non alcoholic Fatty Liver Disease	Associate	35790963
Obesity	Stimulate	27056885
Obesity	Associate	27765769, 37063877
Periodontitis	Associate	37063877
Polycystic Ovary Syndrome	Associate	22904171, 27056885
Psoriasis	Associate	34122426
Seizures	Associate	38166692
Sjogren's Syndrome	Associate	29070082
Squamous Cell Carcinoma of Head and Neck	Inhibit	34971930
ST Elevation Myocardial Infarction	Stimulate	31245869
Urinary Bladder Neoplasms	Associate	34589136
Uterine Cervical Dysplasia	Associate	21119665