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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NAXE
NAD(P)HX epimerase
Chromosome 1 Β· 1q22
NCBI Gene: 128240Ensembl: ENSG00000163382.14HGNC: HGNC:18453UniProt: Q8NCW5
58PubMed Papers
21Diseases
0Drugs
22Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsprouting angiogenesisregulation of cholesterol effluxnegative regulation of angiogenesisencephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathymitochondrial diseaseDecreased total leukocyte countgenetic disorder
✦AI Summary

NAXE (NAD(P)HX epimerase) catalyzes the epimerization of damaged NAD(P)H forms (NAD(P)HX) generated through enzymatic or heat-dependent hydration, enabling subsequent repair by NAD(P)HX-hydrate dehydratase 1. This function is essential for maintaining cellular redox homeostasis, as NAXE deficiency leads to accumulation of toxic NAD(P)HX metabolites and depletion of functional NAD(P)H 2. Beyond metabolite repair, NAXE promotes cholesterol efflux from endothelial cells to HDL, regulating angiogenesis [UniProt reference]. Pathogenic NAXE mutations cause progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1), a severe early-onset neurometabolic disorder characterized by rapidly progressive neurological deterioration, seizures, and often fatal decompensation following infection or fever 34. Disease mechanisms involve acute NAD+ depletion, mitochondrial dysfunction, and impaired antioxidant defense, with altered lipidomics evident during crisis 2. In hepatocellular carcinoma, NAXE downregulation promotes tumor progression through ROS accumulation and HIF-1Ξ± activation, identifying NAXE as a tumor suppressor 5. Niacin supplementation shows promise in ameliorating metabolomic abnormalities and clinical symptoms in NAXE deficiency patients 2.

Sources cited
1
NAXE catalyzes epimerization of NAD(P)HX for cofactor repair
PMID: 35866541
2
NAXE deficiency causes NAD(P)HX accumulation, NAD+ depletion, and mitochondrial dysfunction; niacin provides metabolic correction
PMID: 35637064
3
NAXE mutations cause PEBEL1 with progressive encephalopathy in infants
PMID: 35819538
4
NAXE mutations present with variable onset and neurological manifestations including metabolic stroke
PMID: 39937421
5
NAXE downregulation in hepatocellular carcinoma promotes tumor progression via ROS/HIF-1Ξ± signaling
PMID: 33932069
6
NAXE knockout causes accumulation of S- and R-forms of NAD(P)HX inhibiting metabolic pathways
PMID: 40752251
Disease Associationsβ“˜21
encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathyOpen Targets
0.77Strong
mitochondrial diseaseOpen Targets
0.37Weak
Decreased total leukocyte countOpen Targets
0.23Weak
genetic disorderOpen Targets
0.18Weak
atrial fibrillationOpen Targets
0.14Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
neutropeniaOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.06Suggestive
dominant beta-thalassemiaOpen Targets
0.06Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin H diseaseOpen Targets
0.05Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.05Suggestive
Beta-thalassemia - X-linked thrombocytopeniaOpen Targets
0.05Suggestive
beta-thalassemia-X-linked thrombocytopenia syndromeOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.05Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.05Suggestive
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy 1UniProt
Pathogenic Variants22
NM_144772.3(NAXE):c.664+2T>ALikely pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy|Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2024
NM_144772.3(NAXE):c.128C>A (p.Ser43Ter)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 43
NM_144772.3(NAXE):c.184C>T (p.Gln62Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 62
NM_144772.3(NAXE):c.7_23dup (p.Leu10fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 10
NM_144772.3(NAXE):c.435del (p.Arg145fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 145
NM_144772.3(NAXE):c.385C>T (p.Arg129Ter)Likely pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†2024β†’ Residue 129
NM_144772.3(NAXE):c.502dup (p.Glu168fs)Likely pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†2024β†’ Residue 168
NM_144772.3(NAXE):c.73C>T (p.Gln25Ter)Likely pathogenic
NAXE-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 25
NM_144772.3(NAXE):c.540T>G (p.Tyr180Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 180
NM_144772.3(NAXE):c.668G>A (p.Trp223Ter)Likely pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†2022β†’ Residue 223
NM_144772.3(NAXE):c.536dup (p.Tyr180fs)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†2022β†’ Residue 180
NM_144772.3(NAXE):c.611T>C (p.Leu204Pro)Likely pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†2021β†’ Residue 204
NM_144772.3(NAXE):c.229del (p.Gln77fs)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†2021β†’ Residue 77
NM_144772.3(NAXE):c.468_478delinsATCCCTTTCCTTGGGG (p.Gln157fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 157
NM_144772.3(NAXE):c.565G>A (p.Gly189Ser)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜…β˜†β˜†β˜†β†’ Residue 189
NM_144772.3(NAXE):c.262G>T (p.Gly88Trp)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
β˜†β˜†β˜†β˜†2021β†’ Residue 88
NM_144772.3(NAXE):c.281C>A (p.Ala94Asp)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
β˜†β˜†β˜†β˜†2016β†’ Residue 94
NM_144772.3(NAXE):c.743del (p.Ala248fs)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
β˜†β˜†β˜†β˜†2016β†’ Residue 248
NM_144772.3(NAXE):c.516+1G>APathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
β˜†β˜†β˜†β˜†2016
NM_144772.3(NAXE):c.196C>T (p.Gln66Ter)Pathogenic
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
β˜†β˜†β˜†β˜†2016β†’ Residue 66
View on ClinVar β†—
Related Genes
APOA1Protein interaction98%APOA2Protein interaction98%LRP2Protein interaction98%PNPOProtein interaction93%DCP2Protein interaction77%NAXDProtein interaction74%
Tissue Expression6 tissues
Heart
100%
Liver
74%
Brain
52%
Lung
41%
Ovary
41%
Bone Marrow
26%
Gene Interaction Network
Click a node to explore
NAXEAPOA1APOA2LRP2PNPODCP2NAXD
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8NCW5
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.08LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.77 [0.56–1.08]
RankingsWhere NAXE stands among ~20K protein-coding genes
  • #7,896of 20,598
    Most Researched58
  • #2,105of 5,498
    Most Pathogenic Variants22
  • #10,945of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedNAXE
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
AIBP, NAXE, and Angiogenesis: What's in a Name?
PMID: 28546345
Circ Res Β· 2017
1.00
2
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
PMID: 27290639
J Transl Med Β· 2016
0.90
3
Identification of a novel homozygous mutation in NAXE gene associated with early-onset progressive encephalopathy by whole-exome sequencing: in silico protein structure characterization, molecular docking, and dynamic simulation.
PMID: 35819538
Neurogenetics Β· 2022
0.80
4
Generation and characterisation of four human NAD(P)HX epimerase (NAXE) knockout iPSC lines.
PMID: 40752251
Stem Cell Res Β· 2025
0.70
5
Clinical and biochemical distinctions for a metabolite repair disorder caused by NAXD or NAXE deficiency.
PMID: 35866541
J Inherit Metab Dis Β· 2022
0.60