FTL

Chr 19ADAR

ferritin light chain

Also known as: FTL1, LFTD, NBIA3

The light subunit of ferritin stores iron in a soluble and nontoxic state within cells, with subunit composition affecting iron uptake and release rates across tissues. Mutations cause hyperferritinemia-cataract syndrome, L-ferritin deficiency, and neurodegeneration with brain iron accumulation type 3 through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves dominant-negative effects where mutant protein disrupts normal ferritin function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 1.953 OMIM phenotypes
Clinical SummaryFTL
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -1.51
OE 1.62 (0.961.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.44Z-score
OE missense 1.13 (0.961.33)
106 obs / 94.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.62 (0.961.95)
00.351.4
Missense OE1.13 (0.961.33)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 11 / 6.8Missense obs/exp: 106 / 94.0Syn Z: 0.06
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFTL-related hereditary hyperferritinemia-cataract syndromeLOFAD
DN
0.7132th %ile
GOF
0.6246th %ile
LOF
0.2970th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
LOF1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNActing in a dominant negative manner, mutations are responsible for an impairment of the iron storage efficiency of ferritin molecule.PMID:25772441
LOFWe conclude that haploinsufficiency of FTL may be associated with hypoferritinemia without neurological dysfunction.PMID:33548513

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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