NOX1

protein-coding

NADPH oxidase 1

Gene summary

This gene encodes a member of the NADPH oxidase family of enzymes responsible for the catalytic one-electron transfer of oxygen to generate superoxide or hydrogen peroxide. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

MANE transcript

NM_007052.5

Inheritance

ClinVar variants

U:106B:19

Top phenotype

NOX1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chrX:100,843,324-100,874,359

External References & Databases

Ensembl (ENSG00000007952)

Transcript & Mutation Effects

hg38 • Region Span ~31.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inflammatory bowel diseaseLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0005265

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NOX1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 68

not providedTotal: 17

NOX1-related disorderTotal: 8

Very early onset inflammatory bowel diseaseTotal: 1

NeuroferritinopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007052.5. 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			6 clinvar	2 clinvar	1 clinvar	9
missense			86 clinvar	13 clinvar	2 clinvar	101
nonsense			5 clinvar	1 clinvar		6
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	106	16	3	125

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007052.5	RefSeq	NP_008983.2	13	MANE Select
ENST00000372966.8	Ensembl	ENSP00000362057.3	13	MANE Select
NM_001271815.2	RefSeq	NP_001258744.1	12	Standard
NM_013955.3	RefSeq	NP_039249.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)
Osteoclast differentiation - Homo sapiens (human)
TNF alpha Signaling Pathway
Vitamin D Receptor Pathway

Biological Process

angiogenesis
regulation of systemic arterial blood pressure by renin-angiotensin
NADP metabolic process
defense response
inflammatory response

Molecular Function

voltage-gated ion channel activity
protein binding
superoxide-generating NADPH oxidase activity
metal ion binding
Rac GTPase binding

Cellular Component

early endosome
plasma membrane
cell junction
NADPH oxidase complex
invadopodium membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372966
Coding exons: 13
Length: 31022
Individuals with no LoFs: 125658
Homozygous LoFs: 46
Heterozygous LoFs: 40
Defined: 125744
p: 0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0507	210	208	1.01	0.0000157	3709
Missense (PolyPhen)		74	80.507	0.91917		1613
Synonymous	0.993	62	72.8	0.852	0.00000514	1051
Loss of Function	1.34	14	20.6	0.680	0.00000159	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0.00026	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00019	rare
South Asian	0.0023	0.0014	notable
Other	0.0011	0.00082	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain.;

Recessive Scores

pRec: 0.282

Intolerance Scores

LoFtool: 0.134
RVIS EVS: 0.42
RVIS percentile EVS: 77.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.163

Gene Damage Prediction

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