This gene belongs to the HLA class I heavy chain paralogues. It encodes a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in som... See more...

Aliases for HLA-F Gene

Aliases for HLA-F Gene

  • Major Histocompatibility Complex, Class I, F 2 3 5
  • HLA Class I Histocompatibility Antigen, Alpha Chain F 3 4
  • MHC Class I Antigen F 3 4
  • Leukocyte Antigen F 3 4
  • HLA F Antigen 3 4
  • HLA-5.4 3 4
  • CDA12 3 4
  • HLAF 3 4
  • HLA-CDA12 3
  • HLA-F 5

External Ids for HLA-F Gene

Previous GeneCards Identifiers for HLA-F Gene

  • GC06P029748
  • GC06P029461
  • GC06P029800
  • GC06P029801
  • GC06P029802
  • GC06P029690
  • GC06P029499
  • GC06P029853
  • GC06P030080
  • GC06P032165
  • GC06P032409
  • GC06P032547
  • GC06P033159
  • GC06P030326
  • GC06P030478
  • GC06P030678
  • GC06P030840
  • GC06P031001
  • GC06P031160
  • GC06P031332
  • GC06P031579

Summaries for HLA-F Gene

Entrez Gene Summary for HLA-F Gene

  • This gene belongs to the HLA class I heavy chain paralogues. It encodes a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in some cell types. It contains a divergent peptide-binding groove, and is thought to bind a restricted subset of peptides for immune presentation. This gene exhibits few polymorphisms. Multiple transcript variants encoding different isoforms have been found for this gene. These variants lack a coding exon found in transcripts from other HLA paralogues due to an altered splice acceptor site, resulting in a shorter cytoplasmic domain. [provided by RefSeq, Jul 2008]

GeneCards Summary for HLA-F Gene

HLA-F (Major Histocompatibility Complex, Class I, F) is a Protein Coding gene. Among its related pathways are Antigen processing-Cross presentation and Actin Nucleation by ARP-WASP Complex. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and TAP1 binding. An important paralog of this gene is HLA-A.

UniProtKB/Swiss-Prot Summary for HLA-F Gene

  • Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation. Functions in two forms, as a heterotrimeric complex with B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, presents non-canonical self-peptides carrying post-translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory receptor, a major player in maternal-fetal tolerance. Peptide-free OC acts as a ligand for KIR3DS1 and KIR3DL2 receptors (PubMed:28636952). Upon interaction with activating KIR3DS1 receptor on NK cells, triggers NK cell degranulation and anti-viral cytokine production (PubMed:27455421). Through interaction with KIR3DL2 receptor, inhibits NK and T cell effector functions (PubMed:24018270). May interact with other MHC class I OCs to cross-present exogenous viral, tumor or minor histompatibility antigens to cytotoxic CD8+ T cells, triggering effector and memory responses (PubMed:23851683). May play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, may protect motor neurons from astrocyte-induced toxicity (PubMed:26928464).

Gene Wiki entry for HLA-F Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HLA-F Gene

Genomics for HLA-F Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HLA-F Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HLA-F on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HLA-F

Top Transcription factor binding sites by QIAGEN in the HLA-F gene promoter:
  • AML1a
  • Bach2
  • GATA-2
  • HOXA5
  • Ik-3
  • ISGF-3
  • p300
  • SREBP-1b
  • SREBP-1c
  • Zic3

Genomic Locations for HLA-F Gene

Genomic Locations for HLA-F Gene
chr6:29,722,775-29,740,355
(GRCh38/hg38)
Size:
17,581 bases
Orientation:
Plus strand
chr6:29,690,552-29,706,305
(GRCh37/hg19)
Size:
15,754 bases
Orientation:
Plus strand

Genomic View for HLA-F Gene

Genes around HLA-F on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HLA-F Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HLA-F Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Proteins for HLA-F Gene

  • Protein details for HLA-F Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P30511-HLAF_HUMAN
    Recommended name:
    HLA class I histocompatibility antigen, alpha chain F
    Protein Accession:
    P30511
    Secondary Accessions:
    • Q5JQI8
    • Q5JQJ1
    • Q5SPT5
    • Q860R0
    • Q8MGQ1
    • Q8WLP5
    • Q95HC0
    • Q9TP68

    Protein attributes for HLA-F Gene

    Size:
    346 amino acids
    Molecular mass:
    39062 Da
    Quaternary structure:
    • Forms a heterotrimer with B2M and a self-peptide (PubMed:28636952). Binds a diverse number of peptides ranging from 7 to more than 30 amino acids (PubMed:28636952). Peptide-bound HLA-F-B2M interacts with LILRB1 and LILRB2 but not with KIR3DS1 or KIR3DL2; this interaction is direct (PubMed:28636952, PubMed:11169396). The OC form interacts with KIR3DS1, KIR2DS4 and KIR3DL2; this interaction is direct (PubMed:28636952, PubMed:27455421, PubMed:24018270). Interacts with TAP1-TAP2 complex and CALR; this interaction is required for appropriate folding and peptide loading (PubMed:10605026, PubMed:11169396). Interacts with the coat protein complex II and 14-3-3 proteins; these interactions likely control the anterograde ER-to-Golgi transport of HLA-F (PubMed:16709803). HLA-F-B2M complex interacts with the heavy chain of other MHC class I molecules including HLA-A and HLA-E; this interaction may regulate the intracellular trafficking and the stability of peptide-free MHC class I OCs (PubMed:20483783).
    SequenceCaution:
    • Sequence=AAC24827.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAH09260.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB63337.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAA34947.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAB46623.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HLA-F Gene

    Alternative splice isoforms for HLA-F Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HLA-F Gene

Post-translational modifications for HLA-F Gene

No data available for DME Specific Peptides for HLA-F Gene

Domains & Families for HLA-F Gene

Gene Families for HLA-F Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for HLA-F Gene

InterPro:
Blocks:
  • Immunoglobulin C-type
  • MHC class I signature
  • MHC_I, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for HLA-F Gene

GenScript: Design optimal peptide antigens:
  • Major histocompatibility complex, class I, F (A2AAS2_HUMAN)
  • Major histocompatibility complex, class I, F (A2AAS3_HUMAN)
  • Major histocompatibility complex, class I, F (A2AAS4_HUMAN)
  • Major histocompatibility complex, class I, F (A2ACE9_HUMAN)
  • Major histocompatibility complex, class I, F (A2ACF0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P30511

UniProtKB/Swiss-Prot:

HLAF_HUMAN :
  • Belongs to the MHC class I family.
Family:
  • Belongs to the MHC class I family.
genes like me logo Genes that share domains with HLA-F: view

Function for HLA-F Gene

Molecular function for HLA-F Gene

UniProtKB/Swiss-Prot Function:
Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation. Functions in two forms, as a heterotrimeric complex with B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, presents non-canonical self-peptides carrying post-translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory receptor, a major player in maternal-fetal tolerance. Peptide-free OC acts as a ligand for KIR3DS1 and KIR3DL2 receptors (PubMed:28636952). Upon interaction with activating KIR3DS1 receptor on NK cells, triggers NK cell degranulation and anti-viral cytokine production (PubMed:27455421). Through interaction with KIR3DL2 receptor, inhibits NK and T cell effector functions (PubMed:24018270). May interact with other MHC class I OCs to cross-present exogenous viral, tumor or minor histompatibility antigens to cytotoxic CD8+ T cells, triggering effector and memory responses (PubMed:23851683). May play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, may protect motor neurons from astrocyte-induced toxicity (PubMed:26928464).
UniProtKB/Swiss-Prot Induction:
Up-regulated in CD4+ T cells upon stimulation via TCR and upon HIV-1 infection.
GENATLAS Biochemistry:
HLA class Ib,44kDa,5.4kb HindIII fragment,TAP and tapasin dependent,expression at the cell surface,correlating with the binding of an MHC class I leader peptide (see MHC1)

Phenotypes From GWAS Catalog for HLA-F Gene

Gene Ontology (GO) - Molecular Function for HLA-F Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IBA 21873635
GO:0005515 protein binding IPI 10605026
GO:0030881 beta-2-microglobulin binding IDA 28636952
GO:0042605 peptide antigen binding IDA 23851683
GO:0046978 TAP1 binding IPI 10605026
genes like me logo Genes that share ontologies with HLA-F: view
genes like me logo Genes that share phenotypes with HLA-F: view

Animal Model Products

CRISPR Products

miRNA for HLA-F Gene

miRTarBase miRNAs that target HLA-F

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HLA-F

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for HLA-F Gene

Localization for HLA-F Gene

Subcellular locations from UniProtKB/Swiss-Prot for HLA-F Gene

Cell membrane. Single-pass type I membrane protein. Early endosome membrane. Lysosome membrane. Note=For cross-presentation transits from the cell surface through endosomal pathway to lysosomes, where the peptide is generated from internalized exogenous antigen. {ECO:0000269 PubMed:23851683}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HLA-F gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
endosome 5
lysosome 5
golgi apparatus 5
extracellular 4
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1

Gene Ontology (GO) - Cellular Components for HLA-F Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005615 extracellular space IBA 21873635
GO:0005764 lysosome IEA --
GO:0005765 lysosomal membrane IEA,IDA 23851683
GO:0005768 endosome IEA --
genes like me logo Genes that share ontologies with HLA-F: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HLA-F Gene

Pathways & Interactions for HLA-F Gene

genes like me logo Genes that share pathways with HLA-F: view

SIGNOR curated interactions for HLA-F Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for HLA-F Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001916 positive regulation of T cell mediated cytotoxicity IBA,IMP 23851683
GO:0002376 immune system process IEA --
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I TAS --
GO:0002476 antigen processing and presentation of endogenous peptide antigen via MHC class Ib IDA 28636952
GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib IDA 23851683
genes like me logo Genes that share ontologies with HLA-F: view

Drugs & Compounds for HLA-F Gene

No Compound Related Data Available

Transcripts for HLA-F Gene

mRNA/cDNA for HLA-F Gene

3 REFSEQ mRNAs :
24 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HLA-F

Alternative Splicing Database (ASD) splice patterns (SP) for HLA-F Gene

No ASD Table

Relevant External Links for HLA-F Gene

GeneLoc Exon Structure for
HLA-F

Expression for HLA-F Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HLA-F Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HLA-F Gene

This gene is overexpressed in Whole Blood (x9.1) and Spleen (x5.5).

Protein differential expression in normal tissues from HIPED for HLA-F Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.4), Skin (13.0), NK cells (8.9), and CD8 Tcells (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HLA-F Gene



Protein tissue co-expression partners for HLA-F Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HLA-F

SOURCE GeneReport for Unigene cluster for HLA-F Gene:

Hs.519972

mRNA Expression by UniProt/SwissProt for HLA-F Gene:

P30511-HLAF_HUMAN
Tissue specificity: Expressed in resting B cells (at protein level). Expressed in secondary lymphoid organs rich in B and T cells such as the tonsils, spleen, and thymus (at protein level) (PubMed:10605026, PubMed:11169396). Expressed in the endothelial cells of the tonsils (PubMed:11169396). Expressed on activated lymphoid cells including B cells, NK cells, CD4+ T cells and memory T cells (at protein level) (PubMed:27455421, PubMed:20865824). Expressed in motor neurons of spinal cord (PubMed:26928464).

Evidence on tissue expression from TISSUES for HLA-F Gene

  • Lung(4.6)
  • Spleen(3)
  • Intestine(2.7)
  • Blood(2.7)
  • Nervous system(2.3)
  • Liver(2.2)
  • Lymph node(2.2)
  • Heart(2.1)
genes like me logo Genes that share expression patterns with HLA-F: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HLA-F Gene

Orthologs for HLA-F Gene

This gene was present in the common ancestor of mammals.

Orthologs for HLA-F Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PATR-F 30
  • 98.16 (n)
PATR-AL 31
  • 72 (a)
ManyToMany
Dog
(Canis familiaris)
Mammalia DLA-79 30
  • 77.47 (n)
Mouse
(Mus musculus)
Mammalia Gm7030 30 17
  • 74.52 (n)
Gm11127 17
Species where no ortholog for HLA-F was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for HLA-F Gene

ENSEMBL:
Gene Tree for HLA-F (if available)
TreeFam:
Gene Tree for HLA-F (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HLA-F: view image

Paralogs for HLA-F Gene

genes like me logo Genes that share paralogs with HLA-F: view

Variants for HLA-F Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HLA-F Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
rs1736924 - p.Pro272Ser
rs17875379 - p.Ala13Val
rs17875380 - p.Pro71Gln

Additional dbSNP identifiers (rs#s) for HLA-F Gene

Structural Variations from Database of Genomic Variants (DGV) for HLA-F Gene

Variant ID Type Subtype PubMed ID
dgv992e201 CNV deletion 23290073
esv25966 CNV gain+loss 19812545
nsv1074389 CNV deletion 25765185
nsv10809 CNV gain 18304495
nsv1122126 CNV deletion 24896259
nsv1144137 CNV deletion 24896259
nsv428139 CNV gain 18775914
nsv462673 CNV loss 19166990
nsv508397 CNV deletion 20534489
nsv601230 CNV loss 21841781
nsv970101 CNV duplication 23825009

Variation tolerance for HLA-F Gene

Residual Variation Intolerance Score: 79.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.80; 83.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HLA-F Gene

Human Gene Mutation Database (HGMD)
HLA-F
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HLA-F

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HLA-F Gene

Disorders for HLA-F Gene

Additional Disease Information for HLA-F

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform

No disorders were found for HLA-F Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for HLA-F Gene

Publications for HLA-F Gene

  1. Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element. (PMID: 1688605) Geraghty DE … Koller BH (The Journal of experimental medicine 1990) 2 3 4 23
  2. Genetic associations of common deletion polymorphisms in families with Avellino corneal dystrophy. (PMID: 19622345) Park M … Kim HL (Biochemical and biophysical research communications 2009) 3 23 41
  3. SNP mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians. (PMID: 17971048) Burfoot RK … Rubio JP (Tissue antigens 2008) 3 23 41
  4. HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes. (PMID: 16570139) Pyo CW … Geraghty DE (Immunogenetics 2006) 3 4 23
  5. Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors. (PMID: 28636952) Dulberger CL … Adams EJ (Immunity 2017) 3 4

Products for HLA-F Gene

  • Signalway ELISA kits for HLA-F
  • Signalway Proteins for HLA-F

Sources for HLA-F Gene