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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FTH1
ferritin heavy chain 1
Chromosome 11 · 11q12.3
NCBI Gene: 2495Ensembl: ENSG00000167996.17HGNC: HGNC:3976UniProt: P02794
256PubMed Papers
22Diseases
0Drugs
4Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ferroxidase activityprotein bindingferrous iron bindingidentical protein bindingneurodegeneration with brain iron accumulation 9Retinal dystrophyautosomal recessive bestrophinopathyhemochromatosis type 5
✦AI Summary

FTH1 (ferritin heavy chain 1) is the primary iron storage protein that maintains cellular iron homeostasis by sequestering iron in a soluble, non-toxic form and preventing iron-mediated oxidative damage. FTH1 functions as a critical regulator of ferroptosis, an iron-dependent form of programmed cell death characterized by lipid peroxidation 12. The protein undergoes ferritinophagy, a selective autophagy process mediated by the cargo receptor NCOA4, which degrades FTH1 to release stored iron 34. Under pathological conditions, excessive FTH1 degradation leads to iron accumulation and ferroptosis induction 5. FTH1 expression is regulated by transcription factors including STAT3, which binds to FTH1 promoter elements to enhance its expression as part of ferroptosis resistance mechanisms 6. Clinically, FTH1 dysregulation contributes to multiple diseases including Parkinson's disease, where reduced FTH1 promotes neuronal ferroptosis 3, gastric cancer chemoresistance through ferroptosis evasion 6, and chr11 kidney disease-associated vascular calcification 4. The protein also plays protective roles in inflammatory conditions like psoriasis and ulcerative colitis by preventing ferroptosis-mediated tissue damage 78. These findings establish FTH1 as a crucial therapeutic target for ferroptosis-related disorders.

Sources cited
1
FTH1 prevents ferroptosis by blocking autophagic degradation and ferrous ion release in doxorubicin-induced cardiotoxicity
PMID: 38984448
2
Silibinin protects against acute kidney injury by binding FTH1 and disrupting NCOA4-FTH1 interaction to inhibit ferritinophagy
PMID: 39326069
3
STAT3 regulates FTH1 expression by binding to its promoter as part of ferroptosis negative regulation in gastric cancer
PMID: 35483272
4
Melatonin inhibits ferroptosis through SIRT6/NCOA4/FTH1 pathway to protect against age-related cataracts
PMID: 36463827
5
FTH1 expression is decreased in psoriatic lesions, correlating with increased ferroptosis susceptibility
PMID: 34707088
6
FTH1 levels are decreased in DSS-induced ulcerative colitis associated with ferroptosis
PMID: 32540488
7
FTH1 inhibits ferroptosis through ferritinophagy regulation involving NCOA4 in Parkinson's disease model
PMID: 32959272
8
NCOA4/FTH1-mediated ferritinophagy promotes ferroptosis in chronic kidney disease vascular calcification
PMID: 39613734
Disease Associationsⓘ22
neurodegeneration with brain iron accumulation 9Open Targets
0.54Moderate
Retinal dystrophyOpen Targets
0.53Moderate
autosomal recessive bestrophinopathyOpen Targets
0.53Moderate
hemochromatosis type 5Open Targets
0.52Moderate
vitelliform macular dystrophy 2Open Targets
0.52Moderate
FTH1-related iron overloadOpen Targets
0.49Moderate
Stargardt diseaseOpen Targets
0.45Moderate
autosomal dominant vitreoretinochoroidopathyOpen Targets
0.44Moderate
retinitis pigmentosaOpen Targets
0.41Moderate
retinitis pigmentosa 50Open Targets
0.37Weak
CHARGE syndromeOpen Targets
0.34Weak
severe early-childhood-onset retinal dystrophyOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
Tangier diseaseOpen Targets
0.16Weak
BEST1-related dominant retinopathyOpen Targets
0.16Weak
cone-rod dystrophy 6Open Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
spondylolisthesisOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
Hemochromatosis 5UniProt
Neurodegeneration with brain iron accumulation 9UniProt
Pathogenic Variants4
NM_002032.3(FTH1):c.512_513del (p.Leu170_Phe171insTer)Pathogenic
Neurodegeneration with brain iron accumulation 9|not provided
★★☆☆2025→ Residue 170
NM_002032.3(FTH1):c.497T>A (p.Leu166Ter)Pathogenic
Neurodegeneration with brain iron accumulation 9
★☆☆☆2025→ Residue 166
NM_002032.3(FTH1):c.487_490dup (p.Ser164Ter)Pathogenic
Neurodegeneration with brain iron accumulation 9
☆☆☆☆2024→ Residue 164
NM_002032.3(FTH1):c.-164A>TPathogenic
Hemochromatosis type 5
☆☆☆☆2001
View on ClinVar ↗
Related Genes
TFRCProtein interaction96%SLC11A2Protein interaction92%ALBProtein interaction91%SCARA5Protein interaction85%SLC40A1Protein interaction83%SF1Protein interaction83%
Tissue Expression6 tissues
Brain
100%
Lung
67%
Ovary
27%
Liver
26%
Bone Marrow
18%
Heart
10%
Gene Interaction Network
Click a node to explore
FTH1TFRCSLC11A2ALBSCARA5SLC40A1SF1
PROTEIN STRUCTURE
Preparing viewer…
PDB6B8F · 1.06 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.40Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.15 [0.07–0.40]
RankingsWhere FTH1 stands among ~20K protein-coding genes
  • #1,499of 20,598
    Most Researched256 · top 10%
  • #3,690of 5,498
    Most Pathogenic Variants4
  • #1,965of 17,882
    Most Constrained (LOEUF)0.40 · top quartile
Genes detectedFTH1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Protosappanin A Protects DOX-Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis-Dependent Ferroptosis.
PMID: 38984448
Adv Sci (Weinh) · 2024
1.00
2
Silibinin attenuates ferroptosis in acute kidney injury by targeting FTH1.
PMID: 39326069
Redox Biol · 2024
0.90
3
Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer.
PMID: 35483272
Redox Biol · 2022
0.80
4
Melatonin inhibits ferroptosis and delays age-related cataract by regulating SIRT6/p-Nrf2/GPX4 and SIRT6/NCOA4/FTH1 pathways.
PMID: 36463827
Biomed Pharmacother · 2023
0.70
5
Extracellular SQSTM1 exacerbates acute pancreatitis by activating autophagy-dependent ferroptosis.
PMID: 36426912
Autophagy · 2023
0.64