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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SFXN2
sideroflexin 2
Chromosome 10 · 10q24.32
NCBI Gene: 118980Ensembl: ENSG00000156398.13HGNC: HGNC:16086UniProt: A0A0C4DGR6
50PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrial transmembrane transportprotein bindingmitochondrial outer membranemitochondrionatrial fibrillationUterine leiomyomatinea unguiumdermatophytosis
✦AI Summary

SFXN2 (sideroflexin 2) is a mitochondrial transmembrane protein that functions as an amino acid transporter mediating serine import into mitochondria 1. Its primary role involves regulating mitochondrial iron homeostasis by controlling heme biosynthesis 2. SFXN2 knockout cells exhibit elevated mitochondrial iron accumulation with decreased heme content and heme-dependent enzyme activities, ultimately impairing mitochondrial respiration 2. The protein also suppresses mitochondrial autophagy and mitophagy while promoting iron-mediated energy production to support cell proliferation 3. In disease contexts, SFXN2 dysregulation has emerging clinical significance. In multiple myeloma, elevated SFXN2 expression correlates with poor outcomes and promotes proliferation through mitochondrial bioenergetics and iron metabolism regulation 3, while kaempferol-induced SFXN2 downregulation triggers apoptosis through iron dysregulation and mitophagy 4. In breast cancer, high SFXN2 expression associates with favorable prognosis, contrasting with other family members 5. Cross-ancestry genome-wide association studies identified SFXN2 as a schizophrenia risk gene missed in European-only datasets 6. SFXN2 also appears relevant to chr10 kidney disease progression as part of predictive gene panels 7. These findings establish SFXN2 as a critical regulator of mitochondrial metabolism with diverse roles in cancer and neuropsychiatric disease.

Sources cited
1
SFXN2 mediates serine transport into mitochondria
PMID: 30442778
2
SFXN2 regulates mitochondrial iron homeostasis and heme biosynthesis; knockout increases mitochondrial iron and decreases heme content
PMID: 30570704
3
Elevated SFXN2 suppresses mitophagy and promotes iron-mediated energy production to enhance multiple myeloma cell proliferation
PMID: 36163342
4
Kaempferol-induced SFXN2 downregulation disrupts iron metabolism and induces mitophagy and apoptosis in multiple myeloma
PMID: 40812598
5
High SFXN2 expression associates with good prognosis in breast cancer patients
PMID: 37020524
6
SFXN2 identified as schizophrenia risk gene in cross-ancestry brain eQTL analysis, missed in European-only datasets
PMID: 39362218
7
SFXN2 included in gene sets for chronic kidney disease progression prediction
PMID: 40894929
8
SFXN2 implicated in mitochondrial iron regulation and heme biosynthesis as part of SFXN family functions
PMID: 40542427
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.41Moderate
Uterine leiomyomaOpen Targets
0.31Weak
tinea unguiumOpen Targets
0.22Weak
dermatophytosisOpen Targets
0.20Weak
MenorrhagiaOpen Targets
0.17Weak
diabetic eye diseaseOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
Miyoshi myopathyOpen Targets
0.07Suggestive
hearing lossOpen Targets
0.06Suggestive
diabetic retinopathyOpen Targets
0.06Suggestive
hypertensionOpen Targets
0.04Suggestive
schizophreniaOpen Targets
0.04Suggestive
coronary artery diseaseOpen Targets
0.03Suggestive
clear cell renal carcinomaOpen Targets
0.03Suggestive
prostate cancerOpen Targets
0.03Suggestive
strokeOpen Targets
0.02Suggestive
Parkinson diseaseOpen Targets
0.02Suggestive
diabetes mellitusOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SFXN4Shared pathway100%LASP1Shared pathway67%SFXN3Shared pathway60%SFXN5Shared pathway53%PLP2Shared pathway40%TPTEShared pathway40%
Tissue Expression6 tissues
Liver
100%
Ovary
72%
Bone Marrow
44%
Lung
19%
Heart
12%
Brain
11%
Gene Interaction Network
Click a node to explore
SFXN2SFXN4LASP1SFXN3SFXN5PLP2TPTE
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96NB2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.82 [0.62–1.10]
RankingsWhere SFXN2 stands among ~20K protein-coding genes
  • #8,876of 20,598
    Most Researched50
  • #11,246of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedSFXN2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Cross-ancestry analysis of brain QTLs enhances interpretation of schizophrenia genome-wide association studies.
PMID: 39362218
Am J Hum Genet · 2024
1.00
2
Comprehensive analysis of the role of SFXN family in breast cancer.
PMID: 37020524
Open Med (Wars) · 2023
0.90
3
Kaempferol induces mitophagy and disrupts iron metabolism via SFXN2 leading to apoptosis in multiple myeloma cells.
PMID: 40812598
Free Radic Biol Med · 2025
0.80
4
Elevated SFXN2 limits mitochondrial autophagy and increases iron-mediated energy production to promote multiple myeloma cell proliferation.
PMID: 36163342
Cell Death Dis · 2022
0.70
5
Update of the sideroflexin (SLC56) gene family.
PMID: 40542427
Hum Genomics · 2025
0.60