NOXO1

protein-coding

NADPH oxidase organizer 1

Gene summary

This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

MANE transcript

NM_172167.3

Inheritance

—

ClinVar variants

U:91B:10

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 1.06

Max pathogenic AF

—

Genomic locus

chr16:1,978,917-1,984,192

External References & Databases

Ensembl (ENSG00000196408)

Transcript & Mutation Effects

hg38 • Region Span ~5.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NOXO1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172167.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			89 clinvar	8 clinvar		97
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	91	10	0	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172167.3	RefSeq	NP_751907.1	8	MANE Select
ENST00000356120.9	Ensembl	ENSP00000348435.4	8	MANE Select
NM_001267721.2	RefSeq	NP_001254650.1	8	Standard
NM_144603.4	RefSeq	NP_653204.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TNF alpha Signaling Pathway
Signal Transduction
RHO GTPases Activate NADPH Oxidases
RHO GTPase Effectors
Signaling by Rho GTPases

Biological Process

superoxide metabolic process
regulation of hydrogen peroxide metabolic process
extracellular matrix disassembly
positive regulation of catalytic activity
regulation of respiratory burst

Molecular Function

protein binding
phospholipid binding
superoxide-generating NADPH oxidase activator activity
enzyme binding
phosphatidylinositol binding

Cellular Component

plasma membrane
NADPH oxidase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397280
Coding exons: 8
Length: 5276
Individuals with no LoFs: 123047
Homozygous LoFs: 20
Heterozygous LoFs: 2550
Defined: 125617
p: 0.0103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.811	252	218	1.15	0.0000127	2257
Missense (PolyPhen)		84	67.332	1.2476		765
Synonymous	-1.31	115	98.4	1.17	0.00000568	842
Loss of Function	-0.213	15	14.1	1.06	6.90e-7	149

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0033	0.0028	notable
Latino/Admixed American	0.0082	0.0076	notable
Ashkenazi Jewish	0.020	0.019	notable
East Asian	0.0047	0.0047	notable
Finnish	0.0083	0.0072	notable
European (Non-Finnish)	0.017	0.015	notable
South Asian	0.0023	0.0021	notable
Other	0.016	0.015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Constitutively potentiates the superoxide-generating activity of NOX1 and NOX3 and is required for the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. Isoform 3 is more potent than isoform 1 in activating NOX3. Together with NOXA1, may also substitute to NCF1/p47phox and NCF2/p67phox in supporting the phagocyte NOX2/gp91phox superoxide-generating activity. {ECO:0000269|PubMed:12657628, ECO:0000269|PubMed:14617635, ECO:0000269|PubMed:15326186, ECO:0000269|PubMed:15824103, ECO:0000269|PubMed:15949904, ECO:0000269|PubMed:16329988, ECO:0000269|PubMed:17126813, ECO:0000269|PubMed:19755710}.;

Recessive Scores

pRec: 0.139

Intolerance Scores

LoFtool: 0.961
RVIS EVS: 0.24
RVIS percentile EVS: 69.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.402

Gene Damage Prediction

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