PLPBP

Last update 08 May 2025

Basic Info

Synonyms

PLP homeostasis protein, PLPBP, Proline synthase co-transcribed bacterial homolog protein

+ [4]

Introduction

Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6.

100 Clinical Results associated with PLPBP

100 Translational Medicine associated with PLPBP

0 Patents (Medical) associated with PLPBP

Literatures (Medical) associated with PLPBP

01 Feb 2025·Translational Cancer Research

The causal effects of 2,821 protein level ratios on non-small cell lung cancer: a two-sample Mendelian randomization study

Article

Author: Zou, Xinyun ; Shen, Jinlan ; Li, Xiaokai ; Zhang, Ling ; Diao, Yong

BackgroundNon-small cell lung cancer (NSCLC) has a complex etiology, making early diagnosis difficult and leading to high mortality rates, thus necessitating personalized treatment strategies. While protein level ratios have shown potential as biomarkers or therapeutic targets, their causal relationship with NSCLC remains unclear. This study aimed to investigate these causal links using Mendelian randomization (MR), providing insights into potential biomarkers and therapeutic avenues.MethodsWe executed an intricate two-sample MR study to explore the stochastic causal links between 2,821 protein level ratios and NSCLC. The genome-wide association study (GWAS) statistics for NSCLC and protein level ratios were sourced from the Finnish Database (version 10) and the UK Biobank, respectively. For the instrumental variables (IVs) related to protein level ratios, we selected IVs with a P value <1.0×10^-5. Throughout this analysis, we applied five established MR techniques.ResultsOur study identified causal relationships between 142 protein level ratios and NSCLC. Notably, the AKR1B1/SUGT1 protein level ratio and the PLPBP/STIP1 protein level ratio demonstrated the most significant negative correlations with NSCLC risk. On the other hand, the ARHGEF12/IRAK4 protein level ratio and the BANK1/LBR protein level ratio exhibited the most significant positive correlations. Furthermore, sensitivity analyses did not reveal any significant heterogeneity or horizontal pleiotropy.ConclusionsStudying specific protein level ratios in patients can reveal the molecular mechanisms and pathological processes of NSCLC, which has certain clinical significance for early diagnosis of NSCLC, understanding drug resistance mechanisms and developing personalized treatment strategies. However, these findings necessitate further validation through extensive clinical research.

01 Sep 2023·Journal of Inherited Metabolic Disease

On pathways and blind alleys—The importance of biomarkers in vitamin B₆‐dependent epilepsies

Review

Author: Plecko, Barbara

AbstractOver the past two decades, the field of vitamin B6‐dependent epilepsies has evolved by the recognition of a growing number of gene defects (ALDH7A1,PNPO, ALPL, ALDH4A1, PLPBP as well as defects of the glycosylphosphatidylinositol anchor proteins) that all lead to reduced availability of pyridoxal 5′‐phosphate, an important cofactor in neurotransmitter and amino acid metabolism. In addition, positive pyridoxine response has been observed in other monogenic defects such as MOCS2 deficiency or KCNQ2 and there may be more defects to be discovered. Most entities lead to neonatal onset pharmaco‐resistant myoclonic seizures or even status epilepticus and pose an emergency to the treating physician. Research has unraveled specific biomarkers for several of these entities (PNPO deficiency, ALDH7A1 deficiency, ALDH4A1 deficiency, ALPL deficiency causing congenital hypophosphatasia and glycosylphosphatidylinositol anchoring defects with hyperphosphatasia), that can be detected in plasma or urine, while there is no biomarker to test for PLPHP deficiency. Secondary elevation of glycine or lactate was recognized as diagnostic pitfall. An algorithm for a standardized trial with vitamin B6 should be in place in every newborn unit in order not to miss these well‐treatable inborn errors of metabolism. The Komrower lecture of 2022 provided me with the opportunity to tell the story about the conundrums of research into vitamin B6‐dependent epilepsies that kept some surprises and many novel insights into pathomechanisms of vitamin metabolism. Every single step had benefits for the patients and families that we care for and advocates for a close collaboration of clinician scientists with basic research.

01 Sep 2023·The Journal of biological chemistry

Maintenance of cellular vitamin B₆ levels and mitochondrial oxidative function depend on pyridoxal 5'-phosphate homeostasis protein.

Article

Author: Bosma, Marjolein ; Zwartkruis, Fried J T ; van Karnebeek, Clara D M ; van Roermund, Carlo W T ; Wanders, Ronald J A ; Jans, Judith J ; Verhoeven-Duif, Nanda M ; IJlst, Lodewijk ; Houten, Sander M ; Waterham, Hans R ; Gerrits, Johan ; Ciapaite, Jolita

Recently, biallelic variants in PLPBP coding for pyridoxal 5'-phosphate homeostasis protein (PLPHP) were identified as a novel cause of early-onset vitamin B₆-dependent epilepsy. The molecular function and precise role of PLPHP in vitamin B₆ metabolism are not well understood. To address these questions, we used PLPHP-deficient patient skin fibroblasts and HEK293 cells and YBL036C (PLPHP ortholog)-deficient yeast. We showed that independent of extracellular B₆ vitamer type (pyridoxine, pyridoxamine, or pyridoxal), intracellular pyridoxal 5'-phosphate (PLP) was lower in PLPHP-deficient fibroblasts and HEK293 cells than controls. Culturing cells with pyridoxine or pyridoxamine led to the concentration-dependent accumulation of pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate (PMP), respectively, suggesting insufficient pyridox(am)ine 5'-phosphate oxidase activity. Experiments utilizing ¹³C₄-pyridoxine confirmed lower pyridox(am)ine 5'-phosphate oxidase activity and revealed increased fractional turnovers of PLP and pyridoxal, indicating increased PLP hydrolysis to pyridoxal in PLPHP-deficient cells. This effect could be partly counteracted by inactivation of pyridoxal phosphatase. PLPHP deficiency had a distinct effect on mitochondrial PLP and PMP, suggesting impaired activity of mitochondrial transaminases. Moreover, in YBL036C-deficient yeast, PLP was depleted and PMP accumulated only with carbon sources requiring mitochondrial metabolism. Lactate and pyruvate accumulation along with the decrease of tricarboxylic acid cycle intermediates downstream of α-ketoglutarate suggested impaired mitochondrial oxidative metabolism in PLPHP-deficient HEK293 cells. We hypothesize that impaired activity of mitochondrial transaminases may contribute to this depletion. Taken together, our study provides new insights into the pathomechanisms of PLPBP deficiency and reinforces the link between PLPHP function, vitamin B₆ metabolism, and mitochondrial oxidative metabolism.

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

PLPBP

Basic Info

Related

Analysis