FTH1

Chr 11AD

ferritin heavy chain 1

ENSG00000167996UniProt: P02794

Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation (PubMed:9003196). Also plays a role in delivery of iron to cells (By similarity). Mediates iron uptake in capsule cells of the developing kidney (By similarity). Delivery to lysosomes is mediated by the cargo receptor NCOA4 for autophagic degradation and release of iron (PubMed:24695223, PubMed:26436293)

Primary Disease Associations & Inheritance

?Hemochromatosis, type 5MIM #615517
AD
Neurodegeneration with brain iron accumulation 9MIM #620669
AD
UniProtHemochromatosis 5
93
ClinVar variants
17
Pathogenic / LP
0.14
pLI score
0
Active trials
Clinical Summary— FTH1
🧬
Gene-Disease Validity (ClinGen)
hemochromatosis type 5 · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 46 VUS of 93 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.140
Z-score 2.05
OE 0.30 (0.14–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.86Z-score
OE missense 0.75 (0.62–0.91)
72 obs / 95.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.14–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.62–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 3 / 10.0Missense obs/exp: 72 / 95.8Syn Z: -0.88

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic7
VUS46
Likely Benign14
Benign14
Conflicting2
10
Pathogenic
7
Likely Pathogenic
46
VUS
14
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
9
0
10
Likely Pathogenic
0
3
4
0
7
VUS
1
28
16
1
46
Likely Benign
0
3
3
8
14
Benign
0
0
11
3
14
Conflicting
—2
Total234431293

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FTH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Hemochromatosis, type 5

MIM #615517

Molecular basis of disorder known

Autosomal dominant

Neurodegeneration with brain iron accumulation 9

MIM #620669

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Protosappanin A Protects DOX-Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis-Dependent Ferroptosis.
Cui J et al.·Adv Sci (Weinh)
2024
ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence.
Qi Z et al.·Autophagy
2024
Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer.
Ouyang S et al.·Redox Biol
2022
Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.
Gupta U et al.·Autophagy
2023Functional
PRMT1 driven PTX3 regulates ferritinophagy in glioma.
Lathoria K et al.·Autophagy
2023
Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate.
Fu D et al.·Nat Commun
2024
The tryptophan metabolite 3-hydroxyanthranilic acid alleviates hyperoxia-induced bronchopulmonary dysplasia via inhibiting ferroptosis.
Ruan Q et al.·Redox Biol
2025
Platycodin D ameliorates polycystic ovary syndrome-induced ovarian damage by upregulating CD44 to attenuate ferroptosis.
Ji R et al.·Free Radic Biol Med
2024
Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain.
You Y et al.·J Extracell Vesicles
2022
Mycobacterium tuberculosis hijacks host TRIM21- and NCOA4-dependent ferritinophagy to enhance intracellular growth.
Dai Y et al.·J Clin Invest
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
STING1 exacerbates iodinated contrast-induced acute kidney injury by promoting ferroptosis through chaperone-mediated autophagic degradation of FTH1.
Wu T et al.·Autophagy
2026
Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer.
Song S et al.·Redox Biol
2026
Kitasamycin overcomes ferroptosis and immunotherapy resistance by targeting the HUWE1-NCOA4-FTH1 axis.
Li D et al.·Autophagy
2026
Epithelial Cell-Specific Prognostic Signature (FTH1, RIT1, WASL, NDRG2, KIFC3) Stratifies Cervical Cancer Patients and Correlates With Immune Infiltration.
Wang X et al.·Hum Mutat
2026🔓 Open AccessCohort
Morin induces ferroptosis in endometrial cancer cells by down-regulating FTH1.
Hua N et al.·J Mol Histol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools