NOX4

NADPH oxidase 4

Basic information

Region (hg38): 11:89324352-89498187

Links

ENSG00000086991 ∙ NCBI:50507 ∙ OMIM:605261 ∙ HGNC:7891 ∙ Uniprot:Q9NPH5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOX4 gene.

• Inborn genetic diseases (22 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOX4 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				2	1	3
missense			22	1	1	24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	22	3	3

Variants in NOX4

This is a list of pathogenic ClinVar variants found in the NOX4 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-89337490-T-C		not specified	Uncertain significance (Apr 07, 2022)
11-89340101-G-A			Benign (Jul 31, 2018)
11-89340125-C-T		not specified	Uncertain significance (Mar 24, 2023)
11-89340134-A-G		not specified	Uncertain significance (Oct 25, 2023)
11-89340134-A-T		not specified	Uncertain significance (Feb 11, 2022)
11-89342199-G-A			Benign (Apr 06, 2018)
11-89354977-G-T		not specified	Uncertain significance (Feb 14, 2023)
11-89400055-C-T		not specified	Uncertain significance (Jun 01, 2023)
11-89400225-C-A		not specified	Uncertain significance (Nov 12, 2021)
11-89400283-T-C		not specified	Uncertain significance (Jun 30, 2023)
11-89400316-G-A		not specified	Uncertain significance (Apr 11, 2023)
11-89400337-C-T		not specified	Uncertain significance (Jul 26, 2022)
11-89400338-G-C			Benign (Aug 02, 2017)
11-89400364-A-C		not specified	Uncertain significance (May 04, 2022)
11-89400368-C-A		not specified	Uncertain significance (Jun 29, 2023)
11-89400368-C-G		not specified	Uncertain significance (Dec 11, 2023)
11-89402500-G-A			Likely benign (Apr 06, 2018)
11-89402530-C-A		not specified	Uncertain significance (Mar 14, 2023)
11-89421913-C-A		not specified	Uncertain significance (Feb 14, 2023)
11-89432820-A-G		not specified	Uncertain significance (Feb 07, 2023)
11-89432829-A-G		not specified	Uncertain significance (Aug 10, 2021)
11-89432830-C-A		not specified	Uncertain significance (Jul 25, 2023)
11-89444230-C-T		not specified	Uncertain significance (Sep 06, 2022)
11-89449478-A-C		not specified	Uncertain significance (Dec 12, 2023)
11-89449498-C-A			Likely benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOX4	protein_coding	protein_coding	ENST00000263317	18	265256

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.76e-20	0.0224	125663	0	85	125748	0.000338

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.898	340	296	1.15	0.0000144	3759
Missense in Polyphen		94	97.019	0.96889		1252
Synonymous	-3.37	151	107	1.41	0.00000516	1067
Loss of Function	0.857	33	38.8	0.851	0.00000213	446

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000973	0.000929
Ashkenazi Jewish	0.00	0.00
East Asian	0.000402	0.000381
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000199	0.000193
Middle Eastern	0.000402	0.000381
South Asian	0.00113	0.00111
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.
• Pathway: AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Thyroid hormone synthesis;Angiogenesis overview;Spinal Cord Injury;Oxidative Stress;Detoxification of Reactive Oxygen Species;Cellular responses to stress;Cellular responses to external stimuli;Signaling events mediated by PTP1B (Consensus)

Recessive Scores

• pRec: 0.330

Intolerance Scores

• loftool: 0.0754
• rvis_EVS: 0.11
• rvis_percentile_EVS: 62.1

Haploinsufficiency Scores

• pHI: 0.200
• hipred: Y
• hipred_score: 0.593
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.190

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nox4
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; respiratory 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); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cell morphogenesis;response to hypoxia;heart process;superoxide metabolic process;defense response;inflammatory response;cell aging;negative regulation of cell population proliferation;gene expression;positive regulation of smooth muscle cell migration;electron transport chain;cellular response to oxidative stress;superoxide anion generation;positive regulation of apoptotic process;positive regulation of MAP kinase activity;bone resorption;homocysteine metabolic process;positive regulation of stress fiber assembly;positive regulation of protein kinase B signaling;cardiac muscle cell differentiation;oxidation-reduction process;positive regulation of protein tyrosine kinase activity;positive regulation of ERK1 and ERK2 cascade;cellular response to cAMP;cellular response to glucose stimulus;cellular response to gamma radiation;cellular response to transforming growth factor beta stimulus;reactive oxygen species metabolic process;reactive oxygen species biosynthetic process;positive regulation of reactive oxygen species metabolic process;positive regulation of DNA biosynthetic process
• Cellular component: stress fiber;nucleus;nucleolus;mitochondrion;endoplasmic reticulum membrane;plasma membrane;focal adhesion;integral component of membrane;apical plasma membrane;NADPH oxidase complex;perinuclear region of cytoplasm;perinuclear endoplasmic reticulum
• Molecular function: nucleotide binding;protein binding;electron transfer activity;NAD(P)H oxidase activity;superoxide-generating NADPH oxidase activity;oxygen sensor activity;heme binding;flavin adenine dinucleotide binding;modified amino acid binding;protein tyrosine kinase binding