NIPA2: Non-Imprinted in Prader-Willi/Angelman Syndrome Region 2
A magnesium transporter gene implicated in neurodevelopmental disorders and metabolic regulation
Gene Information Card
| Symbol | NIPA2 |
|---|---|
| Full Name | Non-Imprinted in Prader-Willi/Angelman Syndrome Region 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 15q11.2 |
| NCBI Gene ID | 81614 ncbi.nlm.nih.gov/gene/81614 |
| Ensembl ID | ENSG00000140157 |
| UniProt ID | Q8N8Q9 |
| OMIM ID | 608391 |
| HGNC ID | 17044 |
| Aliases | NIPA2, FLJ20489, MGC138290 |
Description
NIPA2 encodes a magnesium transporter protein that belongs to the NIPA family. It is located in the Prader-Willi/Angelman syndrome region on chromosome 15q11.2 and is not imprinted. The protein functions as a selective magnesium ion channel, playing a critical role in cellular magnesium homeostasis. NIPA2 is widely expressed, with highest levels in brain, kidney, and placenta. Mutations in NIPA2 have been associated with neurodevelopmental disorders, including epilepsy and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, childhood absence | Loss of NIPA2 function reduces intracellular magnesium, altering neuronal excitability and seizure susceptibility. | ClinVar, PMID: 24646667 |
| Intellectual disability | Disrupted magnesium transport impairs synaptic plasticity and cognitive function. | ClinVar, PMID: 24646667 |
| Autism spectrum disorder | Rare variants in NIPA2 may contribute to ASD risk through magnesium dysregulation. | ClinVar, PMID: 24646667 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Kidney | 10.3 | High |
| Placenta | 8.7 | Medium |
| Liver | 5.2 | Medium |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | High expression; used in neuronal studies |
| HEK293 (embryonic kidney) | 12.0 | High expression; common for transporter assays |
| HeLa (cervical carcinoma) | 6.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.215C>T (p.Pro72Leu) | Missense | Rare | Reduced magnesium transport activity |
| c.316G>A (p.Gly106Arg) | Missense | Rare | Impaired protein stability and function |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish magnesium transport, leading to cellular magnesium deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • magnesium ion transmembrane transporter activity (GO:0015095) | • magnesium ion transport (GO:0015693) |
| • integral component of membrane (GO:0016021) | • plasma membrane (GO:0005886) |
| • cation transport (GO:0006812) |
Pathways
• Magnesium transport pathway
• Prader-Willi/Angelman syndrome region gene cluster
Protein Summary
NIPA2 is a 360-amino acid transmembrane protein with 9 predicted membrane-spanning domains. It functions as a selective magnesium channel, mediating Mg2+ influx into cells. The protein is localized to the plasma membrane and early endosomes. NIPA2 is highly conserved across species and is essential for maintaining intracellular magnesium levels, which are critical for numerous cellular processes including ATP metabolism, enzyme function, and neuronal signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NIPA2 Knockout HEK293 Cell Line | EDJ-KQ9735 | Human | 81614 | Details Get a Quote |
| NIPA2 Knockout A-549 Cell Line | EDJ-KQ36558 | Human | 81614 | Details Get a Quote |
| NIPA2 Knockout HCT 116 Cell Line | EDJ-KQ36559 | Human | 81614 | Details Get a Quote |
| NIPA2 Knockout HeLa Cell Line | EDJ-KQ36560 | Human | 81614 | Details Get a Quote |
