NOXA1

Chr 9

NADPH oxidase activator 1

Also known as: NY-CO-31, SDCCAG31, p51NOX

NCBI Gene: 10811ENSG00000188747UniProt: Q86UR1

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]

210
ClinVar variants
104
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— NOXA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
104 Pathogenic / Likely Pathogenic· 95 VUS of 210 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.000
Z-score 1.44
OE 0.69 (0.47–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.58Z-score
OE missense 0.90 (0.81–1.00)
233 obs / 259.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.47–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 17 / 24.7Missense obs/exp: 233 / 259.2Syn Z: -0.03

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic10
VUS95
Likely Benign8
Conflicting3
94
Pathogenic
10
Likely Pathogenic
95
VUS
8
Likely Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
94
0
94
Likely Pathogenic
0
0
10
0
10
VUS
0
88
7
0
95
Likely Benign
0
6
1
1
8
Benign
0
0
0
0
0
Conflicting
—3
Total0941121210

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NOXA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NOX1 NADPH oxidase regulation by the NOXA1 SH3 domain.
Valente AJ et al.·Free Radic Biol Med
2007
c-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells.
Gianni D et al.·Mol Biol Cell
2010Functional
Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia.
Zhang J et al.·Virol Sin
2025
Nox activator 1: a potential target for modulation of vascular reactive oxygen species in atherosclerotic arteries.
Niu XL et al.·Circulation
2010
Investigating gene signatures associated with immunity in colon adenocarcinoma to predict the immunotherapy effectiveness using NFM and WGCNA algorithms.
Liang W et al.·Aging (Albany NY)
2024
Death receptors 4 and 5 activate Nox1 NADPH oxidase through riboflavin kinase to induce reactive oxygen species-mediated apoptotic cell death.
Park KJ et al.·J Biol Chem
2012
Cigarette smoke condensate induces MMP-12 gene expression in airway-like epithelia.
Lavigne MC et al.·Biochem Biophys Res Commun
2005
MC1R expression in HaCaT keratinocytes inhibits UVA-induced ROS production via NADPH oxidase- and cAMP-dependent mechanisms.
Henri P et al.·J Cell Physiol
2012Functional
Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species.
Piccoli C et al.·Biochem Biophys Res Commun
2007
Overexpression of human NOX1 complex induces genome instability in mammalian cells.
Chiera F et al.·Free Radic Biol Med
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Sleep ApneaSleep-Disordered Breathing

The Meaning of Dopaminergic Pathway in Sleep Breathing Disorders.

ENROLLING BY INVITATION
NCT05890911Wroclaw Medical UniversityStarted 2023-06-01
PolysomnographyBlood dopamine level measurementGenetical test

External Resources

Links to major genomics databases and tools