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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NIPAL1
NIPA like domain containing 1
Chromosome 4 · 4p12
NCBI Gene: 152519Ensembl: ENSG00000163293.13HGNC: HGNC:27194UniProt: Q6NVV3
11PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membranemagnesium ion transportGolgi apparatusmagnesium ion transmembrane transporter activitygoutself-injurious ideationcholelithiasisbreast carcinoma
✦AI Summary

NIPAL1 (NIPA-like domain containing 1) functions primarily as a magnesium transporter, with the ability to transport other divalent cations including Fe(2+), Sr(2+), Ba(2+), Mn(2+), Cu(2+) and Co(2+), though with much lower efficiency than Mg(2+) 1. The protein localizes to the Golgi apparatus and shows magnesium-dependent expression patterns 1. In pancreatic β-cells, NIPAL1 plays a conditional role in insulin secretion, where knockdown decreases both basal insulin secretion and total insulin content, while overexpression increases insulin content 1. NIPAL1 has emerged as a disease-relevant gene across multiple conditions. It serves as a tumor-promoting factor in oral squamous cell carcinoma, where expression correlates with cancer cell invasion and poorer disease-free survival 2. The gene is associated with gout susceptibility, particularly the renal underexcretion subtype, though functional analysis suggests an indirect role in urate handling 3. NIPAL1 variants are linked to invasive urothelial carcinoma in dogs, accounting for nearly 30% of disease risk in Shetland sheepdogs 4, and show associations with nasopharyngeal carcinoma, bone mineral density, and spondylosis in humans 567. These findings suggest NIPAL1's magnesium transport function may influence diverse pathological processes through altered cellular magnesium homeostasis.

Sources cited
1
NIPAL1 functions as a magnesium transporter, localizes to Golgi apparatus, and regulates insulin secretion in pancreatic β-cells
PMID: 32439805
2
NIPAL1 acts as tumor-promoting factor in oral squamous cell carcinoma and correlates with poor survival
PMID: 29464350
3
NIPAL1 is associated with gout susceptibility, particularly renal underexcretion subtype
PMID: 27899376
4
NIPAL1 mutations increase risk of invasive urothelial carcinoma in Shetland sheepdogs
PMID: 38778091
5
NIPAL1 variants are associated with nasopharyngeal carcinoma susceptibility
PMID: 31289279
6
NIPAL1 shows association with bone mineral density in exome-wide screening
PMID: 36849660
7
NIPAL1 is associated with spondylosis in genome-wide association analysis
PMID: 33332786
Disease Associationsⓘ20
goutOpen Targets
0.40Moderate
self-injurious ideationOpen Targets
0.33Weak
cholelithiasisOpen Targets
0.25Weak
breast carcinomaOpen Targets
0.23Weak
pancreatic adenocarcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
type 2 diabetes mellitusOpen Targets
0.05Suggestive
placental retentionOpen Targets
0.05Suggestive
sign or symptomOpen Targets
0.04Suggestive
oral squamous cell carcinomaOpen Targets
0.04Suggestive
nasopharyngeal carcinomaOpen Targets
0.04Suggestive
esophageal squamous cell carcinomaOpen Targets
0.02Suggestive
Epstein-Barr virus infectionOpen Targets
0.02Suggestive
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.02Suggestive
dermatological toxicityOpen Targets
0.02Suggestive
response to radiationOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
malnutritionOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NIPAL3Shared pathway100%NIPAL2Shared pathway100%NIPA2Shared pathway100%NIPA1Shared pathway100%NIPAL4Shared pathway100%MAGT1Protein interaction66%
Tissue Expression6 tissues
Liver
100%
Brain
5%
Lung
4%
Heart
3%
Ovary
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
NIPAL1NIPAL3NIPAL2NIPA2NIPA1NIPAL4MAGT1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q6NVV3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.30LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.92 [0.67–1.30]
RankingsWhere NIPAL1 stands among ~20K protein-coding genes
  • #16,833of 20,598
    Most Researched11
  • #13,658of 17,882
    Most Constrained (LOEUF)1.30
Genes detectedNIPAL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NIPA-like domain containing 1 is a novel tumor-promoting factor in oral squamous cell carcinoma.
PMID: 29464350
J Cancer Res Clin Oncol · 2018
1.00
2
GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.
PMID: 27899376
Ann Rheum Dis · 2017
0.90
3
The magnesium transporter NIPAL1 is a pancreatic islet-expressed protein that conditionally impacts insulin secretion.
PMID: 32439805
J Biol Chem · 2020
0.80
4
Genome-wide analyses reveals an association between invasive urothelial carcinoma in the Shetland sheepdog and NIPAL1.
PMID: 38778091
NPJ Precis Oncol · 2024
0.70
5
Whole-Exome Sequencing of Nasopharyngeal Carcinoma Families Reveals Novel Variants Potentially Involved in Nasopharyngeal Carcinoma.
PMID: 31289279
Sci Rep · 2019
0.60