NOX3

protein-coding

NADPH oxidase 3

Gene summary

This gene encodes a member of the NOX family of NADPH oxidases. These enzymes have the capacity to generate superoxide and other reactive oxygen species (ROS) and transport electrons across the plasma membrane. The ROS generated by family members have been implicated in numerous biological functions including host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. The protein encoded by this gene is expressed predominantly in the inner ear and is involved in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity.[provided by RefSeq, May 2009]

MANE transcript

NM_015718.3

Inheritance

—

ClinVar variants

U:90B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr6:155,395,368-155,455,839

External References & Databases

Ensembl (ENSG00000074771)

Transcript & Mutation Effects

hg38 • Region Span ~60.5 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 NOX3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015718.3. 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			90 clinvar	4 clinvar		94
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	90	4	1	95

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015718.3	RefSeq	NP_056533.1	13	MANE Select
ENST00000159060.3	Ensembl	ENSP00000159060.2	13	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thyroid hormone synthesis
Signal Transduction
RHO GTPases Activate NADPH Oxidases
RHO GTPase Effectors
Signaling by Rho GTPases

Biological Process

temperature homeostasis
defense response
detection of gravity
superoxide anion generation
otolith development

Molecular Function

superoxide-generating NADPH oxidase activity

Cellular Component

cytoplasm
plasma membrane
NADPH oxidase complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000159060
Coding exons: 13
Length: 60534
Individuals with no LoFs: 125471
Homozygous LoFs: 1
Heterozygous LoFs: 276
Defined: 125748
p: 0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.225	336	325	1.04	0.0000182	3702
Missense (PolyPhen)		134	131.29	1.0207		1505
Synonymous	-1.05	140	125	1.12	0.00000760	1079
Loss of Function	1.32	26	34.4	0.757	0.00000178	372

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0023	0.0023	notable
Latino/Admixed American	0.00072	0.00069	rare
Ashkenazi Jewish	0.0070	0.0070	notable
East Asian	0.0038	0.0038	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00048	0.00047	rare
South Asian	0.00060	0.00059	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: NADPH oxidase which constitutively produces superoxide upon formation of a complex with CYBA/p22phox. Plays a role in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. {ECO:0000269|PubMed:15824103}.;

Recessive Scores

pRec: 0.288

Intolerance Scores

LoFtool: 0.182
RVIS EVS: -0.49
RVIS percentile EVS: 22.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.143

Gene Damage Prediction

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