FTH1

ferritin heavy chain 1, the group of Ferritin subunits

Basic information

Region (hg38): 11:61959718-61967634

Previous symbols: [ "FTHL6" ]

Links

ENSG00000167996 ∙ NCBI:2495 ∙ OMIM:134770 ∙ HGNC:3976 ∙ Uniprot:P02794 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemochromatosis type 5 (Moderate), mode of inheritance: AD
• hemochromatosis type 5 (Supportive), mode of inheritance: AD
• hemochromatosis type 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemochromatosis, type 5	AD	Hematologic	Preventive measures to ameliorate iron overload may be beneficial	Hematologic; Neurologic	11389486; 37660254

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FTH1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FTH1 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			1	5	5	11
missense			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding			7	4	4	15
Total	0	0	22	10	9

Variants in FTH1

This is a list of pathogenic ClinVar variants found in the FTH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-61959791-A-G			Likely benign (May 20, 2021)
11-61959869-CT-C			not provided (-)
11-61959873-TTC-T			Likely benign (Jul 07, 2023)
11-61959878-T-C			Likely benign (Aug 22, 2022)
11-61959884-G-C			Likely benign (Sep 27, 2022)
11-61959892-G-A		Autosomal recessive bestrophinopathy	Pathogenic (Jan 01, 2008)
11-61959892-G-T		Autosomal recessive bestrophinopathy	Uncertain significance (Apr 23, 2020)
11-61959896-C-A			Uncertain significance (Dec 13, 2019)
11-61959897-C-G		Vitelliform macular dystrophy 2 • Retinitis pigmentosa • Autosomal dominant vitreoretinochoroidopathy	Conflicting classifications of pathogenicity (Nov 27, 2023)
11-61959899-T-C		Autosomal recessive bestrophinopathy • Retinal dystrophy	Likely pathogenic (Jan 01, 2022)
11-61959906-T-C			Likely benign (Feb 10, 2023)
11-61959909-GGATGA-G		BEST1-related disorder	Pathogenic (Jan 24, 2024)
11-61959911-A-T		Vitelliform macular dystrophy 2 • Retinal dystrophy	Uncertain significance (Apr 08, 2021)
11-61959912-T-A		Vitelliform macular dystrophy 2	Uncertain significance (Dec 05, 2019)
11-61959913-G-T			Pathogenic (Nov 13, 2023)
11-61959917-T-C		Vitelliform macular dystrophy 2 • BEST1-related disorder	Conflicting classifications of pathogenicity (Jul 14, 2022)
11-61959929-T-C			Uncertain significance (Sep 27, 2022)
11-61959934-C-T		Autosomal dominant vitreoretinochoroidopathy • Vitelliform macular dystrophy 2 • Retinitis pigmentosa	Conflicting classifications of pathogenicity (Nov 01, 2022)
11-61959935-G-A		Retinal dystrophy • BEST1-related disorder	Conflicting classifications of pathogenicity (Nov 27, 2023)
11-61959935-G-C			Uncertain significance (Feb 04, 2022)
11-61959936-GA-G			Pathogenic (Aug 23, 2022)
11-61959944-C-T			Uncertain significance (Oct 24, 2020)
11-61959945-G-A			Likely benign (Nov 29, 2023)
11-61959949-A-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
11-61959950-T-G			Uncertain significance (Jan 29, 2014)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FTH1	protein_coding	protein_coding	ENST00000273550	4	7943

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.140	0.842	124788	0	7	124795	0.0000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.865	72	95.8	0.751	0.00000518	1212
Missense in Polyphen		4	11.014	0.36318		183
Synonymous	-0.879	49	41.8	1.17	0.00000240	324
Loss of Function	2.05	3	9.98	0.301	5.93e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000545	0.0000530
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. 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}.
• Pathway: Necroptosis - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Iron metabolism in placenta;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;Methionine and cysteine metabolism;Iron uptake and transport;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors;Validated targets of C-MYC transcriptional repression (Consensus)

Recessive Scores

• pRec: 0.485

Intolerance Scores

• loftool: 0.169
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.669
• ghis: 0.442

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.976

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fth1
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cellular iron ion homeostasis;intracellular sequestering of iron ion;immune response;negative regulation of cell population proliferation;neutrophil degranulation;negative regulation of fibroblast proliferation;oxidation-reduction process;negative regulation of necrotic cell death
• Cellular component: extracellular region;nucleus;cytoplasm;cytosol;intracellular ferritin complex;autolysosome;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: ferroxidase activity;iron ion binding;protein binding;ferrous iron binding;ferric iron binding;identical protein binding