NAXE

Chr 1AR

NAD(P)HX epimerase

Also known as: AIBP, APOA1BP, PEBEL, YJEFN1

NCBI Gene: 128240 ENSG00000163382 UniProt: Q8NCW5 OMIM: 608862

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The product of this gene interacts with apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoproteins (HDLs). It is secreted into some bodily fluids, and its synthesis and secretion are stimulated in vitro by incubating cells with apoA-I. The human genome contains related pseudogenes. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathyMIM #617186

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.31

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.000

Z-score 0.75

OE 0.78 (0.48–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.61Z-score

OE missense 0.87 (0.76–1.00)

150 obs / 172.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.48–1.31)

0≤0.351.4

Missense OE?0.87 (0.76–1.00)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 10 / 12.9Missense obs/exp: 150 / 172.4Syn Z: 0.12

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

523 rare PASS variants

Rare truncating (LoF)

1 in 830

106 rare PASS variants

Rare synonymous (reference)

1 in 450

153 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NAXE. 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 99	1 in 960
South Asian	~43k	1 in 92	1 in 970
Remaining (unassigned)	~30k	1 in 56	1 in 300
European (Finnish)	~27k	1 in 270	1 in 2,400
Admixed American	~22k	1 in 94	1 in 480
African / African American	~21k	1 in 85	1 in 1,500
East Asian	~20k	1 in 100	1 in 630
Ashkenazi Jewish	~13k	1 in 480	1 in 570
Middle Eastern	~2,884	1 in 63	≈ 1 in 720

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓