FTL

ferritin light chain, the group of Ferritin subunits

Basic information

Region (hg38): 19:48965308-48966879

Links

ENSG00000087086 ∙ NCBI:2512 ∙ OMIM:134790 ∙ HGNC:3999 ∙ Uniprot:P02792 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary hyperferritinemia with congenital cataracts (Definitive), mode of inheritance: AD
• hereditary hyperferritinemia with congenital cataracts (Strong), mode of inheritance: AD
• L-ferritin deficiency (Strong), mode of inheritance: AD
• neuroferritinopathy (Strong), mode of inheritance: AD
• neuroferritinopathy (Moderate), mode of inheritance: AD
• hereditary hyperferritinemia with congenital cataracts (Moderate), mode of inheritance: AD
• hereditary hyperferritinemia with congenital cataracts (Supportive), mode of inheritance: AD
• neuroferritinopathy (Supportive), mode of inheritance: AD
• genetic hyperferritinemia without iron overload (Supportive), mode of inheritance: AD
• L-ferritin deficiency (Supportive), mode of inheritance: AD
• hereditary hyperferritinemia with congenital cataracts (Strong), mode of inheritance: AD
• L-ferritin deficiency (Limited), mode of inheritance: Unknown
• neuroferritinopathy (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
L-ferritin deficiency; Neurodegeneration with brain iron accumulation 3; Hyperferritinemia with or without cataract	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Hematologic; Neurologic; Ophthalmologic	7493028; 8558554; 7669675; 11438811; 11703332; 12200611; 12199804; 12746423; 15173247; 15280904; 15099026; 17142829; 18413574; 18854324; 20301320; 22020773; 22278127 ; 22515742; 23940258

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FTL gene.

• Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy (52 variants)
• Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts (36 variants)
• Hereditary hyperferritinemia with congenital cataracts (30 variants)
• not provided (30 variants)
• Neuroferritinopathy (26 variants)
• not specified (9 variants)
• Inborn genetic diseases (8 variants)
• L-ferritin deficiency;Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy (2 variants)
• FTL-related condition (2 variants)
• sporadic abdominal aortic aneurysm (2 variants)
• L-ferritin deficiency (2 variants)
• Glycogen storage disease due to muscle and heart glycogen synthase deficiency (1 variants)
• - (1 variants)
• L-ferritin deficiency, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FTL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	14	2	19
missense		1	41	2		44
nonsense	1	1	2			4
start loss						0
frameshift	2	2	2			6
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			5	1		6
non coding	6	6	29	5	3	49
Total	9	10	78	21	5

Highest pathogenic variant AF is 0.0000197

Variants in FTL

This is a list of pathogenic ClinVar variants found in the FTL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-48965312-G-C		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Aug 16, 2022)
19-48965315-C-G		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Dec 18, 2022)
19-48965317-GCGGTCCCGCGGGTCTGTCTCTTGCTTCAA-G		Hereditary hyperferritinemia with congenital cataracts	Pathogenic (Feb 19, 2013)
19-48965318-C-T		Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy	Uncertain significance (Jan 08, 2024)
19-48965319-G-C			Uncertain significance (Apr 26, 2022)
19-48965319-G-T		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Oct 02, 2021)
19-48965322-C-A		Neuroferritinopathy • Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Apr 27, 2017)
19-48965322-C-T		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Jan 16, 2024)
19-48965324-C-G		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Nov 03, 2022)
19-48965324-C-T			Uncertain significance (Jul 01, 2023)
19-48965326-C-T		not specified	Uncertain significance (Nov 21, 2023)
19-48965327-G-A		Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy	Uncertain significance (Jun 15, 2023)
19-48965329-G-A		Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy	Uncertain significance (Sep 05, 2023)
19-48965329-GTCTGTC-G		Hereditary hyperferritinemia with congenital cataracts	Pathogenic (Feb 19, 2013)
19-48965330-T-G		-	no classification for the single variant (-)
19-48965331-C-T		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Jul 26, 2023)
19-48965335-C-G		Neuroferritinopathy • Hereditary hyperferritinemia with congenital cataracts • Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy	Uncertain significance (Aug 29, 2023)
19-48965338-T-C		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Uncertain significance (Nov 16, 2023)
19-48965340-G-A		Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Pathogenic (Dec 02, 2023)
19-48965340-G-C		Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Pathogenic/Likely pathogenic (Jun 05, 2023)
19-48965340-G-T		Hereditary hyperferritinemia with congenital cataracts • Hereditary hyperferritinemia with congenital cataracts;Neuroferritinopathy • FTL-related disorder	Pathogenic (Dec 15, 2023)
19-48965341-C-T		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts • Hereditary hyperferritinemia with congenital cataracts	Pathogenic (Jan 16, 2024)
19-48965342-T-C		Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Likely pathogenic (May 21, 2021)
19-48965344-C-A		Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy;Hereditary hyperferritinemia with congenital cataracts	Pathogenic (Oct 11, 2020)
19-48965344-C-T		Hereditary hyperferritinemia with congenital cataracts	Pathogenic (Feb 19, 2013)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FTL	protein_coding	protein_coding	ENST00000331825	4	1578

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.66e-9	0.0178	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.441	106	94.0	1.13	0.00000513	1158
Missense in Polyphen		11	12.858	0.85548		231
Synonymous	0.0635	40	40.5	0.987	0.00000233	337
Loss of Function	-1.51	11	6.77	1.62	2.94e-7	85

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000605	0.000604
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity). {ECO:0000250, ECO:0000269|PubMed:19923220, ECO:0000269|PubMed:20159981}.
• Disease: DISEASE: Hyperferritinemia with or without cataract (HRFTC) [MIM:600886]: An autosomal dominant disease characterized by elevated level of ferritin in serum and tissues, and early-onset bilateral cataract. Cataracts may be subclinical in some patients. {ECO:0000269|PubMed:19176363}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neurodegeneration with brain iron accumulation 3 (NBIA3) [MIM:606159]: A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild non-progressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels. {ECO:0000269|PubMed:16116125}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: L-ferritin deficiency (LFTD) [MIM:615604]: A condition characterized by low levels of ferritin in serum and tissues in the absence of other hematological symptoms. Seizures and mild neuropsychologic impairment may manifest in individuals with complete ferritin deficiency. {ECO:0000269|PubMed:23940258}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Necroptosis - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;Neutrophil degranulation;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Innate Immune System;Immune System;Transport of small molecules;Iron uptake and transport;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors (Consensus)

Recessive Scores

• pRec: 0.648

Intolerance Scores

• loftool: 0.791
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.0829
• hipred: Y
• hipred_score: 0.541
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ftl1
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: iron ion transport;cellular iron ion homeostasis;intracellular sequestering of iron ion;neutrophil degranulation;iron ion homeostasis;oxidation-reduction process
• Cellular component: extracellular region;cytoplasm;cytosol;intracellular ferritin complex;membrane;azurophil granule lumen;autolysosome;extracellular exosome
• Molecular function: ferroxidase activity;iron ion binding;protein binding;ferrous iron binding;ferric iron binding;identical protein binding