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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC25A28
solute carrier family 25 member 28
Chromosome 10 · 10q24.2
NCBI Gene: 81894Ensembl: ENSG00000155287.12HGNC: HGNC:23472UniProt: A0A8V8TR30
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrionferrous iron transmembrane transporter activityiron import into the mitochondrionmitochondrial membranediverticular diseaseFuchs endothelial corneal dystrophyearly-onset non-syndromic cataractazoospermia
✦AI Summary

SLC25A28, also known as mitoferrin-2 (MFRN2), is a mitochondrial iron transporter that mediates iron uptake into mitochondria and plays crucial roles in cellular iron homeostasis 12. The protein is essential for mitochondrial respiration and iron-sulfur cluster protein function, as its deficiency profoundly impairs these processes and leads to DNA damage and cell death 1. SLC25A28 exhibits synthetic lethal interactions with its paralog SLC25A37 (MFRN1), making it an attractive therapeutic target in cancers where SLC25A37 is homozygously deleted 13. The gene demonstrates significant disease relevance in cancer biology, where it promotes ferroptosis - an iron-dependent form of cell death - through mechanisms involving iron accumulation and mitochondrial dysfunction 245. In hepatic stellate cells, SLC25A28 forms complexes with p53 to enhance iron accumulation and electron transport chain hyperfunction, contributing to ferroptotic cell death 2. Clinically, SLC25A28 represents a promising therapeutic target, as knockout mice display minimal toxicity except for cataracts in some animals, suggesting that inhibition strategies may have acceptable safety profiles 3. The protein's role in iron homeostasis and ferroptosis makes it relevant for treating various cancers, liver fibrosis, and other iron-related disorders.

Sources cited
1
SLC25A28 is a mitochondrial iron transporter with synthetic lethal interactions with SLC25A37
PMID: 38886830
2
SLC25A28 forms complexes with p53 and regulates ferroptosis in hepatic stellate cells
PMID: 32863216
3
SLC25A28 knockout mice show minimal toxicity, making it an attractive therapeutic target
PMID: 40968372
4
SLC25A28 promotes ferroptosis in clear cell renal cell carcinoma
PMID: 39922352
5
SLC25A28 regulates electron transport chain disruption and ferroptosis in colorectal cancer
PMID: 41456814
Disease Associationsⓘ20
diverticular diseaseOpen Targets
0.17Weak
Fuchs endothelial corneal dystrophyOpen Targets
0.09Suggestive
early-onset non-syndromic cataractOpen Targets
0.08Suggestive
azoospermiaOpen Targets
0.08Suggestive
Lisch epithelial corneal dystrophyOpen Targets
0.07Suggestive
X-linked endothelial corneal dystrophyOpen Targets
0.07Suggestive
X-linked corneal dermoidOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
posterior polymorphous corneal dystrophyOpen Targets
0.07Suggestive
autosomal dominant keratitisOpen Targets
0.06Suggestive
congenital hereditary endothelial dystrophy of corneaOpen Targets
0.06Suggestive
lattice corneal dystrophy type IOpen Targets
0.06Suggestive
Central cloudy dystrophy of FrancoisOpen Targets
0.06Suggestive
central cloudy dystrophy of FrançoisOpen Targets
0.06Suggestive
Schnyder corneal dystrophyOpen Targets
0.06Suggestive
colorectal cancerOpen Targets
0.06Suggestive
granular corneal dystrophy type IOpen Targets
0.06Suggestive
corneal dystrophy, punctiform and polychromatic pre-descemetOpen Targets
0.06Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.06Suggestive
isolated ectopia lentisOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NARS2Protein interaction90%ABCB8Protein interaction83%MTCH1Protein interaction77%ABCB7Protein interaction74%FECHProtein interaction74%FXNProtein interaction74%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
75%
Lung
75%
Ovary
68%
Heart
45%
Brain
34%
Gene Interaction Network
Click a node to explore
SLC25A28NARS2ABCB8MTCH1ABCB7FECHFXN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96A46
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.58Moderately Constrained
pLIⓘ
0.85Intermediate
Observed/Expected LoF0.34 [0.21–0.58]
RankingsWhere SLC25A28 stands among ~20K protein-coding genes
  • #13,066of 20,598
    Most Researched25
  • #3,821of 17,882
    Most Constrained (LOEUF)0.58 · top quartile
Genes detectedSLC25A28
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PINK1-deficiency facilitates mitochondrial iron accumulation and colon tumorigenesis.
PMID: 39512202
Autophagy · 2025
1.00
2
A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.
PMID: 40968372
Genome Biol · 2025
0.90
3
Mitoferrin2 is a synthetic lethal target for chromosome 8p deleted cancers.
PMID: 38886830
Genome Med · 2024
0.80
4
MEMO1 binds iron and modulates iron homeostasis in cancer cells.
PMID: 38640016
Elife · 2024
0.70
5
Long non-coding RNA ZFAS1 promotes ferroptosis by regulating the miR-185-5p/SLC25A28 axis in clear cell renal cell carcinoma.
PMID: 39922352
Int J Biol Macromol · 2025
0.60