NOXO1

Chr 16

NADPH oxidase organizer 1

Also known as: P41NOX, P41NOXA, P41NOXB, P41NOXC, SH3PXD5, SNX28

NCBI Gene: 124056 ENSG00000196408 UniProt: Q8NFA2 OMIM: 611256

The protein is an NADPH oxidase organizer that potentiates superoxide-generating activity of NOX1 and NOX3 and is required for biogenesis of otoconia, the crystalline structures in the inner ear that detect gravity. Mutations cause autosomal recessive hearing loss with vestibular dysfunction due to absent or malformed otoconia. The gene shows low constraint to loss-of-function variants, consistent with a recessive inheritance pattern affecting primarily inner ear development and function.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.62

Clinical Summary— NOXO1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

87 VUS of 103 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.62LOEUF

pLI 0.000

Z-score -0.21

OE 1.06 (0.71–1.62)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.81Z-score

OE missense 1.15 (1.04–1.28)

252 obs / 218.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.06 (0.71–1.62)

0≤0.351.4

Missense OE?1.15 (1.04–1.28)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 15 / 14.1Missense obs/exp: 252 / 218.3Syn Z: -1.31

This gene — mechanism propensity

0.5674th %ile

GOF

0.6930th %ile

LOF

0.4037th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS87

Likely Benign10

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	86	0	87
Likely Benign	1	8	1	10
Benign	0	0	0	0
Total	2	94	1	97

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap NOXO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →