NIPA2 Membrane Protein Introduction

Introduction of NIPA2

The magnesium transporter NIPA2 is a highly selective magnesium transporter encoded by the NIPA2 gene located in the GGE-associated region 15q11.2. NIPA2 is expressed in the cell membrane and early endosomes. It belongs to the NIPA protein family. NIPA family members (including NIPA1, NIPA2, NIPA3, and NIPA4) are integral membrane proteins responsible for the transport of magnesium ions. Its function is to transfer extracellular Mg2+ to the cytoplasm. Phylogenetic analysis indicated that NIPA2 is highly conserved in vertebrate species and mainly expressed in the brain. The NIPA2 gene includes 10 exons, ranging from exon 6 to exon 10, which encodes a polypeptide having 9 transmembrane domains. Neural network excitability NIPA2 is a highly selective Mg2+ transporter that may play an important role in blocking NMDARs by regulating Mg2+ concentration and therefore plays an important role in excitability.

Basic Information of NIPA2
Protein Name Magnesium transporter NIPA2
Gene Name NIPA2
Aliases Non-imprinted in Prader-Willi/Angelman syndrome region protein 2
Organism Homo sapiens (Human)
UniProt ID Q8N8Q9
Transmembrane Times 9
Length (aa) 360

Function of NIPA2 Membrane Protein

Functional studies indicate that NIPA2 mutation disrupts the transport of the protein to the outer membrane of the cell, resulting in the accumulation of protein in the cytoplasm. The NIPA2 mutation results in inaccurate localization of the NIPA2 protein in neurons and a decrease in intracellular Mg2+. The I178F mutation may inhibit the transport of NIPA2 protein to the cell membrane, but it does not affect the function of the cell membrane. Mutations N244S and N334_E335insD reduce cell membrane concentration and Mg2+ transport. Mg2+ is involved in the gating and activation of channels and receptors, such as the N-methyl-D-aspartate receptor (NMDAR), which is widely distributed in excitatory neurons in the thalamus and cortex where it plays a role in synaptic plasticity. Therefore, a decrease in intracellular Mg2+ concentration caused by a mutation in NIPA2 may result in the occurrence of epilepsy.

The location of the mutation found in NIPA2, a selective Mg2+ transporter. Fig.1 The location of the mutation found in NIPA2, a selective Mg2+ transporter. (Jiang, 2012)

Application of NIPA2 Membrane Protein in Literature

  1. Xie H., et al. Functional Study of NIPA2 Mutations Identified from the Patients with Childhood Absence Epilepsy. Plos One. 2014, 9(10): e109749. PubMed ID: 25347071

    This article finds that selective magnesium transporter NIPA2 may play a role in the pathogenesis of childhood absence epilepsy.

  2. Jiang Y., et al. NIPA2 located in 15q11.2 is mutated in patients with childhood absence epilepsy. Human Genetics. 2012, 131(7): 1217-24. PubMed ID: 22367439

    This article firstly shows that NIPA2 encoding a selective magnesium transporter is a susceptibility gene for childhood absence epilepsy and that a single deficiency of NIPA2 may be a potential mechanism for the neurological phenotype of the 15q11.2 microdeletion.

  3. Goytain A., et al. Functional characterization of NIPA2, a selective Mg2+ transporter. American Journal of Physiology Cell Physiology. 2008, 295(4): C944-53. PubMed ID: 18667602

    This article concludes that NIPA2 plays a role in magnesium metabolism and regulation of renal magnesium ions.

  4. Jiang Y., et al. NIPA2 mutations are correlative with childhood absence epilepsy in the Han Chinese population. Human Genetics. 2014, 133(5): 675-6. PubMed ID: 24500577

    This article suggests that the NIPA2 variant is associated with the childhood absence epilepsy in the Han population.

  5. Hildebrand M.S., et al. Does variation in NIPA2, contribute to genetic generalized epilepsy? Human Genetics. 2014, 133(5): 673-4. PubMed ID: 24408008

    This article shows that at least in the Caucasian population, the NIPA2 gene variant is not associated with hereditary generalized epilepsy.

NIPA2 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-NIPA2 antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.


  1. Jiang Y, et al. (2012). NIPA2 located in 15q11.2 is mutated in patients with childhood absence epilepsy. Human Genetics. 131(7):1217-24.

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