LTF
protein-codinglactotransferrin, the group of Transferrins
Gene summary
This gene is a member of the transferrin family of genes and its protein product is found in the secondary granules of neutrophils. The protein is a major iron-binding protein in milk and body secretions with an antimicrobial activity, making it an important component of the non-specific immune system. The protein demonstrates a broad spectrum of properties, including regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. Antimicrobial, antiviral, antifungal and antiparasitic activity has been found for this protein and its peptides. Activity against both DNA and RNA viruses has been found, including activity against SARS-CoV-2, and HIV. [provided by RefSeq, Jul 2021]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LTF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002343.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 5 | 3 | 11 | ||
| missense | 103 | 12 | 3 | 118 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 110 | 17 | 6 | 133 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002334.2 | 17 | MANE Select | |
| Ensembl | ENSP00000231751.4 | 17 | MANE Select | |
| RefSeq | NP_001186078.1 | 16 | Standard | |
| RefSeq | NP_001308050.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Disease
- Infectious disease
- Antimicrobial peptides
- Innate Immune System
Biological Process
- ossification
- regulation of cytokine production
- retina homeostasis
- innate immune response in mucosa
- proteolysis
Molecular Function
- lipopolysaccharide binding
- DNA binding
- serine-type endopeptidase activity
- cysteine-type endopeptidase inhibitor activity
- iron ion binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- cytoplasm
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000231751
- Coding exons
- 17
- Length
- 49589
- Individuals with no LoFs
- 125447
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 300
- Defined
- 125748
- p
- 0.00120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.226 | 432 | 419 | 1.03 | 0.0000248 | 4614 |
| Missense (PolyPhen) | 124 | 131.76 | 0.94112 | 1529 | ||
| Synonymous | -0.556 | 183 | 174 | 1.05 | 0.0000114 | 1394 |
| Loss of Function | 0.714 | 35 | 39.9 | 0.878 | 0.00000226 | 440 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0076 | 0.0075 | notable |
| Latino/Admixed American | 0.0013 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00076 | 0.00076 | rare |
| Finnish | 0.00034 | 0.00032 | rare |
| European (Non-Finnish) | 0.00091 | 0.00090 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- 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.; FUNCTION: Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection. N-terminal region shows strong antifungal activity against C.albicans. Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site.; FUNCTION: Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.; FUNCTION: Isoform DeltaLf: transcription factor with antiproliferative properties and ability to induce cell cycle arrest. Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELENOH promoters.;
Recessive Scores
- pRec
- 0.320
Intolerance Scores
- LoFtool
- 0.943
- RVIS EVS
- 0.52
- RVIS percentile EVS
- 80.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.618
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |