NOXA1

protein-coding

NADPH oxidase activator 1

Gene summary

This gene encodes a protein which activates NADPH oxidases, enzymes which catalyze a reaction generating reactive oxygen species. The encoded protein contains four N-terminal tetratricopeptide domains and a C-terminal Src homology 3 domain. Interaction between the encoded protein and proteins in the oxidase regulatory complex occur via the tetratricopeptide domains. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Previous symbols:

SDCCAG31

MANE transcript

NM_001256067.2

Inheritance

—

ClinVar variants

U:100B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr9:137,423,350-137,434,406

External References & Databases

Ensembl (ENSG00000188747)

Transcript & Mutation Effects

hg38 • Region Span ~11.1 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 NOXA1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001256067.2. 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			4 clinvar	1 clinvar		5
missense			89 clinvar	6 clinvar		95
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	100	7	0	107

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 91 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001256067.2	RefSeq	NP_001242996.1	14	MANE Select
ENST00000683555.1	Ensembl	ENSP00000507846.1	14	MANE Select
NM_001256068.2	RefSeq	NP_001242997.1	12	Standard
NM_006647.2	RefSeq	NP_006638.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
RHO GTPases Activate NADPH Oxidases
RHO GTPase Effectors
Signaling by Rho GTPases
RAC1 signaling pathway

Biological Process

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

Molecular Function

protein binding
superoxide-generating NADPH oxidase activator activity
SH3 domain binding
enzyme binding
Rac GTPase binding

Cellular Component

cytosol
NADPH oxidase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341349
Coding exons: 14
Length: 11057
Individuals with no LoFs: 125495
Homozygous LoFs: 0
Heterozygous LoFs: 137
Defined: 125632
p: 0.000545

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.578	233	259	0.899	0.0000156	2992
Missense (PolyPhen)		72	90.155	0.79862		1142
Synonymous	-0.0293	121	121	1.00	0.00000814	1017
Loss of Function	1.44	17	24.7	0.688	0.00000125	271

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00034	0.00031	rare
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00024	0.00022	rare
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.00063	0.00062	rare
South Asian	0.00080	0.00075	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as an activator of NOX1, a superoxide- producing NADPH oxidase. Functions in the production of reactive oxygen species (ROS) which participate in a variety of biological processes including host defense, hormone biosynthesis, oxygen sensing and signal transduction. May also activate CYBB/gp91phox and NOX3. {ECO:0000269|PubMed:12657628, ECO:0000269|PubMed:12716910, ECO:0000269|PubMed:14617635, ECO:0000269|PubMed:14978110, ECO:0000269|PubMed:15181005, ECO:0000269|PubMed:15824103, ECO:0000269|PubMed:17602954, ECO:0000269|PubMed:19755710}.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.368
RVIS EVS: 0.76
RVIS percentile EVS: 86.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.818

Gene Damage Prediction

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