TF

transferrin, the group of Transferrins

Basic information

Region (hg38): 3:133746039-133796641

Links

ENSG00000091513 ∙ NCBI:7018 ∙ OMIM:190000 ∙ HGNC:11740 ∙ Uniprot:P02787 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atransferrinemia (Strong), mode of inheritance: AR
• atransferrinemia (Supportive), mode of inheritance: AR
• atransferrinemia (Limited), mode of inheritance: AR
• atransferrinemia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atransferrinemia	AR	Hematologic	The condition, which involves microcytic anemia and iron overload, can have insidious, nonspecific, and severe manifestations that may include congestive heart failure, and treatment with plasma infusion has been described as effective	Hematologic	13906010; 4625559; 8317485; 11110675; 15466165; 18097132; 19579082

ClinVar

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

• not provided (111 variants)
• Atransferrinemia (59 variants)
• Inborn genetic diseases (20 variants)
• not specified (6 variants)
• (3 variants)
• Iron deficiency anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TF 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			4	36	9	49
missense			35	7	5	47
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	14		15
non coding			7	26	5	38
Total	0	0	47	69	19

Variants in TF

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

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

Position	Type	Phenotype	Significance	ClinVar
3-133746324-G-A		Atransferrinemia	Uncertain significance (Jan 13, 2018)
3-133746357-G-T		Atransferrinemia	Benign (Mar 06, 2018)
3-133746376-G-C		Atransferrinemia	Likely benign (Jan 12, 2018)
3-133746423-C-T		Atransferrinemia	Uncertain significance (Apr 27, 2017)
3-133746439-A-G		Atransferrinemia • not specified	Benign (Jan 13, 2018)
3-133746446-G-A			Likely benign (Jun 06, 2023)
3-133746449-C-T			Likely benign (Jan 13, 2024)
3-133746452-C-T			Likely benign (Jul 13, 2023)
3-133746464-G-T			Likely benign (Aug 03, 2023)
3-133746465-C-T			Likely benign (Jan 31, 2024)
3-133746476-C-T			Likely benign (Jul 19, 2023)
3-133746491-C-A		Atransferrinemia	Conflicting classifications of pathogenicity (Jan 28, 2024)
3-133746492-G-C			Likely benign (May 07, 2023)
3-133746498-G-A			Likely benign (Aug 02, 2023)
3-133746498-G-C			Likely benign (Oct 08, 2023)
3-133746498-G-T			Likely benign (Aug 01, 2023)
3-133748398-C-T			Likely benign (Dec 20, 2022)
3-133748401-C-T			Likely benign (Mar 21, 2023)
3-133748403-C-CT			Likely benign (Jan 13, 2023)
3-133748404-TCC-T			Likely benign (Sep 29, 2023)
3-133748406-C-T			Likely benign (Mar 26, 2023)
3-133748408-C-G			Likely benign (Nov 24, 2023)
3-133748408-C-T			Likely benign (Jan 16, 2024)
3-133748422-G-A			Likely benign (Feb 09, 2023)
3-133748428-C-A			Likely benign (Dec 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TF	protein_coding	protein_coding	ENST00000402696	17	33051

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.10e-8	0.998	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.46	304	385	0.790	0.0000220	4577
Missense in Polyphen		118	156.29	0.75502		1918
Synonymous	-1.60	179	154	1.16	0.00000971	1312
Loss of Function	2.72	18	35.4	0.508	0.00000170	459

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000420	0.000420
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
• Disease: DISEASE: Atransferrinemia (ATRAF) [MIM:209300]: A rare autosomal recessive disorder characterized by abnormal synthesis of transferrin leading to iron overload and microcytic hypochromic anemia. {ECO:0000269|PubMed:11110675, ECO:0000269|PubMed:15466165}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HIF-1 signaling pathway - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Iron metabolism in placenta;Differentiation Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Vesicle-mediated transport;Transferrin endocytosis and recycling;Membrane Trafficking;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Transport of small molecules;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Clathrin-mediated endocytosis;Hemostasis;Cargo recognition for clathrin-mediated endocytosis;Iron uptake and transport;EPHB forward signaling;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.948

Intolerance Scores

• loftool: 0.248
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.12

Haploinsufficiency Scores

• pHI: 0.624
• hipred: N
• hipred_score: 0.301
• ghis: 0.718

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.919

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trf
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region 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)

Zebrafish Information Network

• Gene name: tfa
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: retina homeostasis;platelet degranulation;cellular iron ion homeostasis;regulation of protein stability;transferrin transport;iron ion transmembrane transport;regulation of iron ion transport;post-translational protein modification;cellular protein metabolic process;positive regulation of receptor-mediated endocytosis;iron ion homeostasis;membrane organization;cellular response to iron ion;trivalent inorganic cation transport
• Cellular component: extracellular region;extracellular space;early endosome;late endosome;endoplasmic reticulum lumen;clathrin-coated pit;basal plasma membrane;cell surface;endosome membrane;apical plasma membrane;endocytic vesicle;clathrin-coated vesicle membrane;extrinsic component of external side of plasma membrane;cytoplasmic vesicle;vesicle;secretory granule lumen;basal part of cell;perinuclear region of cytoplasm;recycling endosome;extracellular exosome;blood microparticle;HFE-transferrin receptor complex
• Molecular function: protein binding;ferrous iron binding;ferric iron binding;ferric iron transmembrane transporter activity;iron chaperone activity;transferrin receptor binding