NIPA1: Non-Imprinted in Prader-Willi/Angelman Syndrome 1
A magnesium transporter gene implicated in hereditary spastic paraplegia and neurological disorders
Gene Information Card
| Symbol | NIPA1 |
|---|---|
| Full Name | Non-Imprinted in Prader-Willi/Angelman Syndrome 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q11.2 |
| NCBI Gene ID | 123606 ncbi.nlm.nih.gov/gene/123606 |
| Ensembl ID | ENSG00000180113 |
| UniProt ID | Q7Z5J1 |
| OMIM ID | 606145 |
| HGNC ID | 17043 |
| Aliases | SPG6, NIPA, SLC57A1 |
Description
NIPA1 (Non-Imprinted in Prader-Willi/Angelman Syndrome 1) encodes a magnesium transporter that localizes to the endosomal and plasma membranes. It is highly expressed in the brain and spinal cord. Mutations in NIPA1 cause autosomal dominant hereditary spastic paraplegia type 6 (SPG6), characterized by progressive lower limb spasticity and weakness. The gene is located within the Prader-Willi/Angelman syndrome critical region but is not imprinted.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia 6 (SPG6) | Missense mutations (e.g., T45R, G106R) impair magnesium transport and disrupt endosomal trafficking, leading to axonal degeneration | ClinVar, OMIM |
| Prader-Willi syndrome | NIPA1 lies in the 15q11.2 deletion region; haploinsufficiency may contribute to phenotype, but gene is not imprinted | NCBI, OMIM |
| Angelman syndrome | Similar to Prader-Willi, deletion of 15q11.2 includes NIPA1; role in neurodevelopmental features unclear | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 24.3 | High |
| Spinal cord | 18.7 | High |
| Testis | 12.1 | Medium |
| Kidney | 9.8 | Medium |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.6 | Neuronal model |
| HEK293 (embryonic kidney) | 8.4 | Common overexpression system |
| U-87 MG (glioblastoma) | 11.2 | Glial cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.134C>G (p.Thr45Arg) | Missense | Found in SPG6 families | Impaired magnesium transport; dominant negative effect |
| c.316G>A (p.Gly106Arg) | Missense | Rare in SPG6 | Disrupted protein trafficking |
| c.316G>C (p.Gly106Arg) | Missense | Reported in SPG6 | Similar to G106R |
Mutation functional classification
Loss of Function (LOF)
Not established; NIPA1 knockout mice show mild phenotypes
Gain of Function (GOF)
Not reported
Dominant Negative (DN)
Proposed for T45R and G106R mutations; mutant protein interferes with wild-type function
View complete mutation data：
Gene Ontology (GO)
| • Magnesium ion transmembrane transporter activity | • Endosome membrane |
| • Plasma membrane | • Magnesium ion transport |
| • Neuron projection development |
Pathways
• Magnesium transport
• Endosomal recycling
Protein Summary
NIPA1 is a 9-transmembrane domain protein that functions as a selective magnesium transporter. It localizes to early endosomes and the plasma membrane, regulating intracellular magnesium homeostasis. In neurons, NIPA1 is involved in endosomal trafficking and axonal maintenance. Mutations causing SPG6 lead to protein misfolding, impaired transport activity, and accumulation in endosomes, contributing to corticospinal tract degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NIPA1 Knockout HEK293 Cell Line | EDJ-KQ8209 | Human | 123606 | Details Get a Quote |
| NIPA1 Knockout A-549 Cell Line | EDJ-KQ34107 | Human | 123606 | Details Get a Quote |
| NIPA1 Knockout HCT 116 Cell Line | EDJ-KQ34108 | Human | 123606 | Details Get a Quote |
| NIPA1 Knockout HeLa Cell Line | EDJ-KQ32792 | Human | 123606 | Details Get a Quote |
