ENOX1

Chr 13

ecto-NOX disulfide-thiol exchanger 1

Also known as: CNOX, PIG38, bA64J21.1, cCNOX

NCBI Gene: 55068 ENSG00000120658 UniProt: Q8TC92

This protein functions as a plasma membrane terminal oxidase that transfers electrons from cytosolic NAD(P)H to cell surface acceptors, with hydroquinone oxidase and protein disulfide-thiol interchange activities that oscillate on a 24-minute cycle to regulate cellular biological clocks. The gene is highly constrained against loss-of-function variants (pLI near 1, LOEUF 0.649), suggesting that mutations would likely cause severe developmental phenotypes. However, no definitive human disease associations have been established for ENOX1 mutations at this time.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is involved in plasma membrane electron transport pathways. The encoded protein has both a hydroquinone (NADH) oxidase activity and a protein disulfide-thiol interchange activity. The two activities cycle with a periodicity of 24 minutes, with one activity being at its peak when the other is at its lowest. [provided by RefSeq, Dec 2016]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.25

OE 0.43 (0.29–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.03Z-score

OE missense 0.71 (0.64–0.78)

270 obs / 381.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.43 (0.29–0.65)

0≤0.351.4

Missense OE?0.71 (0.64–0.78)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 16 / 37.4Missense obs/exp: 270 / 381.5Syn Z: 0.20

Background carrier burden — how many people carry a rare variant somewhere in ENOX1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

656 rare PASS variants

Rare truncating (LoF)

1 in 1,900

94 rare PASS variants

Rare synonymous (reference)

1 in 150

288 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ENOX1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 2,100
South Asian	~43k	1 in 170	1 in 1,100
Remaining (unassigned)	~30k	1 in 92	1 in 3,800
European (Finnish)	~27k	1 in 480	1 in 2,000
Admixed American	~22k	1 in 94	≈ 1 in 5,600
African / African American	~21k	1 in 99	1 in 3,800
East Asian	~20k	1 in 160	1 in 470
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 83	≈ 1 in 950

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 13 of 14 coding exons well covered in gnomAD exomes; exon 15 marginal. Genomes: all 14.? see exons ↓