QSOX2

Chr 9

quiescin sulfhydryl oxidase 2

Also known as: QSCN6L1, SOXN

The protein catalyzes the oxidation of sulfhydryl groups to disulfides and contributes to disulfide bond formation in secreted proteins. Based on the extremely low pLI score and moderate loss-of-function tolerance, pathogenic variants would likely cause disease through a gain-of-function mechanism, though specific neurological phenotypes associated with QSOX2 mutations have not been established. The inheritance pattern for QSOX2-related disorders remains undefined.

Summary from RefSeq, UniProt, Mechanism
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0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.84
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryQSOX2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.24
OE 0.55 (0.370.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.64Z-score
OE missense 0.91 (0.830.99)
360 obs / 395.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.370.84)
00.351.4
Missense OE0.91 (0.830.99)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 16 / 29.0Missense obs/exp: 360 / 395.6Syn Z: -0.07
DN
0.6839th %ile
GOF
0.7126th %ile
LOF
0.2776th %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

QSOX2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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