NAXE

Chr 1AR

NAD(P)HX epimerase

Also known as: AIBP, APOA1BP, PEBEL, YJEFN1

The NAXE protein catalyzes the epimerization of damaged forms of NAD(P)H and accelerates cholesterol efflux from endothelial cells to high-density lipoprotein. Biallelic mutations cause autosomal recessive progressive encephalopathy with early onset, characterized by brain edema and leukoencephalopathy. The gene shows low constraint to loss-of-function variation (pLI <0.001), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.311 OMIM phenotype
Clinical SummaryNAXE
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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
1.31LOEUF
pLI 0.000
Z-score 0.75
OE 0.78 (0.481.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.61Z-score
OE missense 0.87 (0.761.00)
150 obs / 172.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.481.31)
00.351.4
Missense OE0.87 (0.761.00)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 10 / 12.9Missense obs/exp: 150 / 172.4Syn Z: 0.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNAXE-related lethal neurometabolic disorder of early childhoodLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7035th %ile
GOF
0.5661th %ile
LOF
0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NAXE · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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