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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC41A3
solute carrier family 41 member 3
Chromosome 3 · 3q21.2-q21.3
NCBI Gene: 54946Ensembl: ENSG00000114544.18HGNC: HGNC:31046UniProt: Q96GZ6
26PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmitochondrial magnesium ion transmembrane transportplasma membranemitochondrial inner membraneduodenal ulcerschizophreniacentral nervous system infectionhepatocellular carcinoma
✦AI Summary

SLC41A3 is a Na+/Mg2+ exchanger that serves as a predominant Mg2+ efflux system at the mitochondrial inner membrane 1. The protein belongs to the solute carrier family 41, which shares distant homology with bacterial Mg2+ transporter MgtE 2. In the kidney, SLC41A3 functions as a basolateral Mg2+ extrusion mechanism in the distal convoluted tubule, working alongside CNNM2 to facilitate Na+-dependent Mg2+ export 31. Studies using SLC41A3-knockout mice provide in vivo evidence supporting its role in Mg2+ extrusion 4. The transporter is highly expressed in the distal convoluted tubule and has been validated as a bona fide Mg2+ transporter with sufficient experimental evidence 5. Disease relevance includes associations with sarcopenia, where a deleterious frameshift deletion in SLC41A3 was identified as a risk factor, potentially affecting myogenin expression and muscle maintenance 6. Additionally, SLC41A3 shows altered expression in liver hepatocellular carcinoma, where higher expression correlates with advanced pathological stages and poorer prognosis 7. The protein's dual role in mitochondrial and plasma membrane Mg2+ homeostasis makes it clinically significant for understanding hypomagnesemia and related metabolic disorders.

Sources cited
1
SLC41A3 acts as a Na+/Mg2+ exchanger and basolateral Mg2+ extrusion mechanism in the distal convoluted tubule
PMID: 36633869
2
SLC41A3 belongs to solute carrier family 41 with distant homology to bacterial MgtE transporter
PMID: 36707183
3
SLC41A3 facilitates basolateral Mg2+ extrusion alongside CNNM2 in kidney
PMID: 38871680
4
SLC41A3-knockout mice studies suggest role as Mg2+ extrusion mechanism
PMID: 26446763
5
SLC41A3 is highly expressed in DCT and validated as Mg2+ transporter with sufficient experimental evidence
PMID: 29412701
6
Deleterious frameshift deletion in SLC41A3 identified as sarcopenia risk factor affecting myogenin expression
PMID: 40552851
7
Higher SLC41A3 expression associated with advanced liver hepatocellular carcinoma stages and poorer prognosis
PMID: 34819993
Disease Associationsⓘ20
duodenal ulcerOpen Targets
0.33Weak
schizophreniaOpen Targets
0.27Weak
central nervous system infectionOpen Targets
0.25Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
Autosomal dominant primary hypomagnesemia with hypocalciuriaOpen Targets
0.08Suggestive
familial primary hypomagnesemia with normocalciuria and normocalcemiaOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
intestinal hypomagnesemia 1Open Targets
0.07Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.07Suggestive
seborrheic keratosisOpen Targets
0.06Suggestive
Genetic renal or urinary tract malformationOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
Benign familial choreaOpen Targets
0.05Suggestive
congenital hydronephrosisOpen Targets
0.05Suggestive
familial vesicoureteral refluxOpen Targets
0.05Suggestive
COVID-19Open Targets
0.05Suggestive
familial isolated hypoparathyroidism due to agenesis of parathyroid glandOpen Targets
0.04Suggestive
hypersulfaturiaOpen Targets
0.04Suggestive
dystonia 22, adult-onsetOpen Targets
0.04Suggestive
Spinocerebellar ataxia type 40Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRPM6Protein interaction79%SLC30A6Shared pathway33%SLC9B1Shared pathway33%UNC79Shared pathway33%UNC80Shared pathway33%SLC60A2Shared pathway33%
Tissue Expression6 tissues
Ovary
100%
Heart
58%
Brain
53%
Lung
37%
Bone Marrow
26%
Liver
26%
Gene Interaction Network
Click a node to explore
SLC41A3TRPM6SLC30A6SLC9B1UNC79UNC80SLC60A2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96GZ6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.21LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.94 [0.74–1.21]
RankingsWhere SLC41A3 stands among ~20K protein-coding genes
  • #12,880of 20,598
    Most Researched26
  • #12,723of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedSLC41A3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Magnesium biology.
PMID: 38871680
Nephrol Dial Transplant · 2024
1.00
2
Magnesium reabsorption in the kidney.
PMID: 36633869
Am J Physiol Renal Physiol · 2023
0.90
3
Functional characteristics and therapeutic potential of SLC41 transporters.
PMID: 36707183
J Pharmacol Sci · 2023
0.80
4
SLC41 transporters--molecular identification and functional role.
PMID: 24745990
Curr Top Membr · 2014
0.70
5
Identification of a Risk Allele at SLC41A3 and a Protective Allele HLA-DPB1*02:01 Associated with Sarcopenia in Japanese.
PMID: 40552851
Gerontology · 2025
0.60