ALKBH8

Last update 08 May 2025

Basic Info

Synonyms

ABH8, alkB homolog 8, tRNA methyltransferase, ALKBH8

+ [7]

Introduction

Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323, PubMed:31079898). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys) (PubMed:20308323). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182).

100 Clinical Results associated with ALKBH8

100 Translational Medicine associated with ALKBH8

0 Patents (Medical) associated with ALKBH8

Literatures (Medical) associated with ALKBH8

01 Jan 2025·Ophthalmology

Genome-Wide and Rare Variant Association Studies of Amblyopia in the All of Us Research Program

Article

Author: Oke, Isdin ; Jain, Ashish ; Aboobakar, Inas F ; Jin, Kimberly ; Tesdahl, Corey D ; Whitman, Mary C ; Lee, Kyoung A Viola

PURPOSEAmblyopia is characterized by decreased visual acuity due to abnormal visual experience during development. It affects approximately 3% of the population and is associated with abnormal development of the visual cortex. Despite treatment, many patients have residual visual acuity deficits. This study aimed to explore the genetic contributions to amblyopia.DESIGNCase-control.PARTICIPANTSThe All of Us Research Program includes genotypic and phenotypic data from a diverse population of adults (age ≥ 18 years) across the United States. A total of 764 subjects with amblyopia (based on International Classification of Diseases and Systematized Nomenclature of Medicine codes) and 122 305 controls with no record of amblyopia and with whole genome sequencing data were compared. Only participants of European genetic ancestry were included because of small numbers of affected participants in other ancestral groups.METHODSGenome-wide association study (GWAS) of common variants (minor allele frequency > 1%) and rare variant association study (RVAS) at the gene level for amblyopia of participants in the All of Us Research Program.MAIN OUTCOME MEASURESIndividual single nucleotide polymorphisms (SNPs) significantly associated with amblyopia and genes with significant burden of rare variants in amblyopia.RESULTSThe GWAS revealed 4 loci that approached statistical significance defined as P < 5e-8: rs56105618, rs1349660, rs7958343, and rs138693522. Each of the variants is an expression quantitative trait locus (eQTL) for a gene expressed in the brain or related to neural development. This RVAS revealed 15 genes with a statistically significant (P < 5e-05) different burden of variants: DCP1B, OR12D2, PCDHA4, ALKBH8, NMUR2, OR52P1P, NEU1, CACNB2, PSMA7, LRR1, ZNF831, FSIP2, ZNF654, CES5A, and MPV17, several of which have known roles in neurodevelopment.CONCLUSIONSThe identification of genes linked to amblyopia with roles in neurodevelopment suggests that the neurodevelopmental changes in amblyopia are not only secondary to abnormal visual experience but also may result from the interaction of primary neurodevelopmental deficits with abnormal experience. This potentially explains why some children develop amblyopia and others do not with the same ocular risk factors, may explain differences in treatment outcomes, and suggests new avenues for amblyopia treatment.FINANCIAL DISCLOSURE(S)Proprietary or commercial disclosure may be found after the references.

12 Nov 2024·Proceedings of the National Academy of Sciences

tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory

Article

Author: Ogata, Carlson H. ; Hogan, Caley A. ; Lentini, Jenna M. ; Dumouchel, Jennifer L. ; O’Connor-Giles, Kate M. ; Fu, Dragony ; Storkebaum, Erik ; Madhwani, Kimberly R. ; Mallik, Moushami ; Sayied, Shanzeh

Post-transcriptional modification of RNA regulates gene expression at multiple levels. ALKBH8 is a tRNA-modifying enzyme that methylates wobble uridines in a subset of tRNAs to modulate translation. Through methylation of tRNA-selenocysteine, ALKBH8 promotes selenoprotein synthesis and regulates redox homeostasis. Pathogenic variants in ALKBH8 have been linked to intellectual disability disorders in the human population, but the role of ALKBH8 in the nervous system is unknown. Through in vivo studies in Drosophila , we show that ALKBH8 controls oxidative stress in the brain to restrain synaptic growth and support learning and memory. ALKBH8 null animals lack wobble uridine methylation and exhibit reduced protein synthesis in the nervous system, including a specific decrease in selenoprotein levels. Either loss of ALKBH8 or independent disruption of selenoprotein synthesis results in ectopic synapse formation. Genetic expression of antioxidant enzymes fully suppresses synaptic overgrowth in ALKBH8 null animals, confirming oxidative stress as the underlying cause of dysregulation. ALKBH8 null animals also exhibit associative memory impairments that are reversed by pharmacological antioxidant treatment. Together, these findings demonstrate the critical role of tRNA wobble uridine modification in redox homeostasis in the developing nervous system and reveal antioxidants as a potential therapy for ALKBH8-associated intellectual disability.

01 Sep 2024·iScience

RNA-modifying enzyme Alkbh8 is involved in mouse embryonic development

Article

Author: Honda, Kohei ; Zhao, Yutong ; Ikuma, Kaori ; Hase, Hiroaki ; Nakai, Manami ; Tsujikawa, Kazutake ; Kitae, Kaori ; Okawa, Katsuya

RNAs undergo more than 300 modifications after transcription. Aberrations in RNA modifications can lead to diseases; their involvement in fetal development has been suggested. This study explored the RNA modifications related to fetal development in mice. We quantified changes in RNA modifications present in mouse embryos at each stage: Metaphase II (MII) oocyte; pronucleus; 2-cell; morula; blastocyst; embryonic days (E)10.5, 13.5, 16.5, and 19.5; and newborn (post-natal day [P]0) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Our results confirm that many RNAs undergo dynamic modifications. In particular, 5-methoxycarbonylmethyluridine (mcm5U) modification was distinctive and increased during the fetal period. In Alkbh8-knockout (KO) mice, the tRNA protein translation efficiency was reduced. Proteome analysis revealed that the factors downregulated in Alkbh8-KO mice were associated with red blood cell and protoporphyrin metabolism. Our results suggest that ALKBH8 facilitates changes in tRNA balance in conjunction with mcm5U, which are essential for normal red blood cell differentiation and embryogenesis in mice.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

ALKBH8

Basic Info

Related

Analysis