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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC41A1
solute carrier family 41 member 1
Chromosome 1 · 1q32.1
NCBI Gene: 254428Ensembl: ENSG00000133065.12HGNC: HGNC:19429UniProt: B2RMP2
34PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
magnesium ion transmembrane transportprotein-containing complexmagnesium ion transmembrane transporter activitytransmembrane transporter activityAbnormality of the skeletal systemnephronophthisisnephronophthisis-like nephropathy 2atrial fibrillation
✦AI Summary

SLC41A1 encodes a Na+/Mg2+ exchanger that functions as the predominant Mg2+ efflux system at the plasma membrane 1. Transport activity is driven by the inwardly directed Na+ electrochemical gradient, making it dependent on extracellular Na+ concentration 1. The exchanger is ubiquitously expressed and regulated through phosphorylation by protein kinase A 1. SLC41A1 is essential for systemic magnesium homeostasis; zebrafish slc41a1 knockdown results in renal Mg2+ wasting and decreased whole-organism Mg2+ content 2. At the cellular level, SLC41A1 facilitates circadian Mg2+ fluxes that regulate clock-controlled gene expression and metabolism 3. Dysregulation of SLC41A1 has clinical significance: null mutations cause nephronophthisis-like nephropathy 2 4, and SLC41A1 variants are associated with Parkinson's disease susceptibility 5, with specific polymorphisms showing reduced PD risk in Iranian populations 6. Recent evidence demonstrates that inflammatory stimuli (e.g., LPS) can upregulate SLC41A1 through STAT5A, leading to pathological Mg2+ depletion, mitochondrial dysfunction, and cell death in dental stem cells 7. Additionally, SLC41A1 overexpression correlates with hepatocellular carcinoma progression and immune dysregulation 8.

Sources cited
1
SLC41A1 encodes the Na+/Mg2+ exchanger; transport depends on extracellular Na+ and is regulated by protein kinase A phosphorylation
PMID: 22031603
2
SLC41A1 is essential for renal magnesium reabsorption and whole-organism Mg2+ homeostasis in vivo
PMID: 30417250
3
SLC41A1 generates circadian Mg2+ fluxes that regulate clock-controlled gene expression and metabolism
PMID: 27074515
4
Null mutations in SLC41A1 cause nephronophthisis-like nephropathy; protein links to Parkinson's disease and preeclampsia
PMID: 24745990
5
SLC41A1 variants are identified in Parkinson's disease and nephronophthisis-related ciliopathies
PMID: 36707183
6
SLC41A1 rs11240569 polymorphism associates with reduced Parkinson's disease risk
PMID: 27612022
7
LPS-induced STAT5A activation upregulates SLC41A1, causing Mg2+ depletion, mitochondrial damage, and pyroptosis in dental stem cells
PMID: 40831212
8
SLC41A1 overexpression in hepatocellular carcinoma correlates with tumor progression and immune cell infiltration
PMID: 39628683
Disease Associationsⓘ21
Abnormality of the skeletal systemOpen Targets
0.50Moderate
nephronophthisisOpen Targets
0.46Moderate
nephronophthisis-like nephropathy 2Open Targets
0.36Weak
atrial fibrillationOpen Targets
0.35Weak
sleep apneaOpen Targets
0.26Weak
type 2 diabetes mellitusOpen Targets
0.20Weak
Parkinson diseaseOpen Targets
0.18Weak
nephrolithiasisOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
prostate carcinomaOpen Targets
0.07Suggestive
obesityOpen Targets
0.05Suggestive
FRAXF syndromeOpen Targets
0.05Suggestive
smoking initiationOpen Targets
0.05Suggestive
mosaic variegated aneuploidy syndrome 4Open Targets
0.05Suggestive
hearing lossOpen Targets
0.04Suggestive
attention deficit hyperactivity disorderOpen Targets
0.04Suggestive
substance abuseOpen Targets
0.04Suggestive
overnutritionOpen Targets
0.04Suggestive
Nephronophthisis-like nephropathy 2UniProt
Pathogenic Variants1
NM_173854.6(SLC41A1):c.698G>T (p.Gly233Val)Pathogenic
Nephronophthisis-like nephropathy 2
☆☆☆☆2021→ Residue 233
View on ClinVar ↗
Related Genes
RAB29Protein interaction92%NUCKS1Protein interaction92%SLC45A3Protein interaction92%PM20D1Protein interaction92%CNNM2Protein interaction80%TRPM7Protein interaction80%
Tissue Expression6 tissues
Heart
100%
Brain
14%
Ovary
12%
Lung
9%
Bone Marrow
8%
Liver
3%
Gene Interaction Network
Click a node to explore
SLC41A1RAB29NUCKS1SLC45A3PM20D1CNNM2TRPM7
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IVJ1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.37Tolerant
Observed/Expected LoF0.40 [0.28–0.59]
RankingsWhere SLC41A1 stands among ~20K protein-coding genes
  • #11,243of 20,598
    Most Researched34
  • #5,230of 5,498
    Most Pathogenic Variants1
  • #3,968of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedSLC41A1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Magnesium and Drugs.
PMID: 31035385
Int J Mol Sci · 2019
1.00
2
Human gene SLC41A1 encodes for the Na+/Mg²+ exchanger.
PMID: 22031603
Am J Physiol Cell Physiol · 2012
0.90
3
SLC41 transporters--molecular identification and functional role.
PMID: 24745990
Curr Top Membr · 2014
0.80
4
LPS-Induced Mitochondrial Damage via SLC41A1-Mediated Magnesium Ion Efflux Leads to the Pyroptosis of Dental Stem Cells.
PMID: 40831212
Adv Sci (Weinh) · 2025
0.70
5
Functional characteristics and therapeutic potential of SLC41 transporters.
PMID: 36707183
J Pharmacol Sci · 2023
0.60