Ask about this productRelated genes to: CARKD antibody
- Gene:
- NAXD NIH gene
- Name:
- NAD(P)HX dehydratase
- Previous symbol:
- CARKD
- Synonyms:
- LP3298, FLJ10769
- Chromosome:
- 13q34
- Locus Type:
- gene with protein product
- Date approved:
- 2008-08-14
- Date modifiied:
- 2016-03-09
Related products to: CARKD antibody
Related articles to: CARKD antibody
- Vitamins are essential metabolites that must be obtained from external sources. In modern times, they have become widely available, leading to their ad hoc consumption. We developed a nutritional genomics framework to systematically identify monogenic diseases responsive to micronutrient modulation. Genome-wide CRISPR screens under varying vitamin B2 and B3 levels revealed dozens of candidate disease genes amenable to rescue by individual vitamins. In the vitamin B3 screen, NAD(P)HX dehydratase (NAXD) was the top hit; this enzyme repairs an aberrant, hydrated form of NADH (6-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide [NADHX]), and its loss causes severe neurodevelopmental disease. In our Naxd knockout (KO) mouse, we observed NADHX accumulation, NAD depletion, and impaired serine biosynthesis in neonatal KO brains. Spatial metabolomics, single-nuclei RNA sequencing (snRNA-seq), and histology pinpointed cortical and brain endothelial cell vulnerability. Low-vitamin B3 diets accelerated pathology, whereas vitamin B3 supplementation extended lifespan by more than 40-fold. These findings establish a nutritional genomics framework and demonstrate the therapeutic potential of precision vitamin interventions. - Source: PubMed
Publication date: 2026/02/25
Garg AnkurBlume Skyler YHuynh HelenBarrios Alec MKarabulut Onurkan OZhao QianMidha Ayush DTurner Adam WResnick B VittorioChen XuewenAgrawal AyushiKim JaeYeonChen LiujiRan QitaoRyan Alison MLarson Reece CNegahban MinaNelson Sophia C KYang Andrew CTraglia MichelaThomas ReubenSun RamonParedes MercedesCorces M RyanLin HeningJain Isha H - The vital cofactors NADH and NADPH are prone to hydration, forming hydroxylated redox-inactive derivatives (NADHX and NADPHX) in cells. These damaged metabolites are repaired by two highly conserved enzymes, an NAD(P)HX dehydratase (NAXD) and an NAD(P)HX epimerase (NAXE). Mutations in NAXE or NAXD cause early onset progressive encephalopathy (PEBEL1 or PEBEL2), typically induced by fever or other triggers, and leading to premature death. To advance our comprehension of the disease mechanism and investigate potential therapeutic strategies, we generated zebrafish lines deficient in naxe or naxd using CRISPR/Cas9 technology. While both models accumulated NADHX, only naxd larvae developed a severe phenotype, showing reduced locomotion and early death, which was partially rescued by nicotinic acid supplementation. Both mutant lines displayed signs of dysregulated immune function based on gene expression analyses and increased neutral red staining in the head region, indicating an increased number or activation of microglial cells. Our findings suggest that immune system perturbations play a role in PEBEL disease development, aligning with its inflammatory trigger-induced nature in humans. The naxd model's responsiveness to nicotinic acid underscores its utility for preclinical drug screening. Overall, these models will be instrumental in furthering our understanding of PEBEL disease mechanisms and enhancing translational research efforts. - Source: PubMed
Patraskaki MyrtoSeyedkatouli NajmesadatSchlicker LisaWarmoes Marc OCordero-Maldonado Maria LorenaHeins-Marroquin UrsulaLinster Carole L - This study aims to explore the clinical characteristics of patients with NAD(P)HX metabolic deficiency and their prognosis after nicotinamide treatment. - Source: PubMed
Publication date: 2026/01/23
Xu ChaolongJin HongLi JiuweiLiu ZhimeiZhang WeihuaZhou JiDuan RuoyuLiu YangSong MinhanZhang ZixuanLi TongyueShen DanminZou YingWang JunlingLi HuaJiang HuafangFang Fang - Neurometabolic diseases are a group of genetic disorders caused by defects in metabolic networks. To characterize the clinical, radiological, and molecular phenotype of three patients with variants in the NAXD gene, together with a review of the literature. A retrospective review of medical records was conducted. Three patients with chronic, progressive, recurrent encephalopathy triggered by fever were identified, with two clinically relevant variants in compound heterozygosity in the NAXD (NM_001242882.2) gene. Individuals 1 and 2: c.794_798dup and c.922C>T. Individual 3: c.269G>T and c.922C>T. We report three patients with neurometabolic disease characterized by recurrent progressive encephalopathy, developmental regression, and movement disorders, associated with systemic involvement and inflammatory-appearing central nervous system lesions due to NAXD enzymatic deficiency. The condition follows a febrile episode, often resulting in early mortality. Other cases showed recurrent episodes triggered by febrile events, characterized by encephalopathy, abnormal movements, ataxia, and seizures. The most frequent systemic manifestations included hematological, mucocutaneous, and cardiac involvement. These three patients broaden the clinical and molecular spectrum of NAXD-associated encephalopathy. Given its potential therapeutic implications, this condition should be considered in the differential diagnosis of neuroinflammatory diseases with poor outcomes, especially in cases with multisystem manifestations. - Source: PubMed
Publication date: 2025/11/30
Garcia Rocio VictoriaAráoz Hilda VerónicaPérez María MercedesBuompadre CelesteMontoya Silvina GomezRugilo CarlosLoria Julian SanchezKim JiHyeAschettino GiovannaAlonso CristinaMonges SoledadLoos Mariana - To summarize the long-term efficacy of nicotinamide in treating pediatric early-onset progressive encephalopathy with brain edema and (or) leukoencephalopathy-2 (PEBEL2) caused by NAXD gene variation This was a case report conducted from February 2019 to January 2025. The long-term efficacy of nicotinamide was observed by following up a child with PEBEL2 who received the treatment in the Department of Neurology, Beijing Children's Hospital Affiliated to Capital Medical University. The clinical data included changes in skin lesions, neurological symptoms. The modified Rankin scale (mRS) was used to evaluate the recovery of neurological function. A boy was diagnosed with PEBEL2 caused by NAXD gene variation via genetic testing at Beijing Children's Hospital Affiliated to Capital Medical University in February 2019, when he was 4 years and 6 months of age. Immediately after diagnosis, nicotinamide treatment was initiated at an initial dose of 100 mg/d, which was increased by 100 mg per week and gradually increased to 500 mg/d; meanwhile, other therapeutic drugs were gradually discontinued. After 1 year and 8 months of treatment, the child's skin lesions had completely resolved; at the 2-year follow-up, dystonia in both upper limbs and swallowing dysfunction was alleviated significantly; by 2.5-year follow-up, his cognitive function also showed improvement. When the child was treated with 500 mg/d for 3 years, a rash appeared around the mouth. After the dose was reduced to 250 mg/d, the rash resolved, and the dose of 250 mg/d was maintained until the last follow-up. At the last follow-up in January 2025, the child was 10 years and 5 months of age. His mRS score decreased from 5 (before treatment) to 4. During the 6-year of continuous nicotinamide treatment, the child's condition remained stable without progression. Drug-related skin rashes occurred, but no severe drug-related adverse reactions were observed. PEBEL2 is a treatable mitochondrial disease. Nicotinamide treatment can effectively improve skin lesions and neurological symptoms in PEBEL2 patients, and the long-term administration demonstrates a favorable safety profile. - Source: PubMed
Publication date: 2025/10/14
Xu C LFang FZhou JWang HZhang W HGong SJiang H FLiu Z MLi J W