FTL

Chr 19ADAR

ferritin light chain

Also known as: FTL1, LFTD, NBIA3

NCBI Gene: 2512ENSG00000087086UniProt: P02792

This gene encodes the light subunit of the ferritin protein. Ferritin is the major intracellular iron storage protein in prokaryotes and eukaryotes. It is composed of 24 subunits of the heavy and light ferritin chains. Variation in ferritin subunit composition may affect the rates of iron uptake and release in different tissues. A major function of ferritin is the storage of iron in a soluble and nontoxic state. Defects in this light chain ferritin gene are associated with several neurodegenerative diseases and hyperferritinemia-cataract syndrome. This gene has multiple pseudogenes. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Hyperferritinemia-cataract syndromeMIM #600886
AD
L-ferritin deficiency, dominant and recessiveMIM #615604
ADAR
Neurodegeneration with brain iron accumulation 3MIM #606159
AD
UniProtHyperferritinemia with or without cataract
243
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FTL
🧬
Gene-Disease Validity (ClinGen)
hereditary hyperferritinemia with congenital cataracts · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 144 VUS of 243 total submissions

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.
1.95LOEUF
pLI 0.000
Z-score -1.51
OE 1.62 (0.96–1.95)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.44Z-score
OE missense 1.13 (0.96–1.33)
106 obs / 94.0 exp
Tolerant

Tolerant to missense variation

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.1.62 (0.96–1.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.13 (0.96–1.33)
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.0.99
0≤1.21.6
LoF obs/exp: 11 / 6.8Missense obs/exp: 106 / 94.0Syn Z: 0.06

ClinVar Variant Classifications

243 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic14
VUS144
Likely Benign44
Benign6
Conflicting8
27
Pathogenic
14
Likely Pathogenic
144
VUS
44
Likely Benign
6
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
20
0
27
Likely Pathogenic
3
1
10
0
14
VUS
5
71
63
5
144
Likely Benign
0
1
23
20
44
Benign
0
0
4
2
6
Conflicting
—8
Total147412027243

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

View in ClinVar →

Protein Context — Lollipop Plot

FTL · protein map & ClinVar variants

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

Gene2Phenotype Curations

FTL-related hereditary hyperferritinemia-cataract syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperferritinemia-cataract syndrome

MIM #600886

Molecular basis of disorder known

Autosomal dominant

L-ferritin deficiency, dominant and recessive

MIM #615604

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Neurodegeneration with brain iron accumulation 3

MIM #606159

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — FTL
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PRMT1 driven PTX3 regulates ferritinophagy in glioma.
Lathoria K et al.·Autophagy
2023
Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis.
Zhou T et al.·J Exp Clin Cancer Res
2023
Transcriptome Landscape of Cancer-Associated Fibroblasts in Human PDAC.
Tao M et al.·Adv Sci (Weinh)
2025
Matrix stiffness-dependent PD-L2 deficiency improves SMYD3/xCT-mediated ferroptosis and the efficacy of anti-PD-1 in HCC.
Wang S et al.·J Adv Res
2025
[Hyperferritinaemia-cataract syndrome].
Benneche A et al.·Tidsskr Nor Laegeforen
2020Case report
Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations.
Yan H et al.·Redox Biol
2023Cohort
Multi-omics Analysis Reveals the Propagation Mechanism of Ferroptosis in Acute Kidney Injury.
Hong Y et al.·Inflammation
2025Functional
Nobiletin alleviates cisplatin-induced ototoxicity via activating autophagy and inhibiting NRF2/GPX4-mediated ferroptosis.
Song W et al.·Sci Rep
2024
Genetic Landscape of Dystonia in Asian Indians.
Saini A et al.·Mov Disord Clin Pract
2025
On the complexity of clinical and molecular bases of neurodegeneration with brain iron accumulation.
Tello C et al.·Clin Genet
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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