NOXA1

Chr 9

NADPH oxidase activator 1

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

This gene encodes a protein that activates NADPH oxidases NOX1, NOX3, and CYBB/gp91phox, which produce reactive oxygen species involved in host defense, hormone biosynthesis, and cellular signaling. Mutations cause ataxia-telangiectasia-like disorder, an autosomal recessive condition characterized by progressive cerebellar ataxia, telangiectasias, and immunodeficiency. The gene shows minimal constraint against loss-of-function variants in the population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.03
Clinical SummaryNOXA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.44
OE 0.69 (0.471.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.58Z-score
OE missense 0.90 (0.811.00)
233 obs / 259.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.471.03)
00.351.4
Missense OE0.90 (0.811.00)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 17 / 24.7Missense obs/exp: 233 / 259.2Syn Z: -0.03
DN
0.6357th %ile
GOF
0.75top 25%
LOF
0.3261th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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