HLA-F
protein-codingmajor histocompatibility complex, class I, F, the group of C1-set domain containing|Histocompatibility complex
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.8 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 HLA-F variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001098479.2. 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 | 2 | 2 | ||||
| missense | 3 | 3 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 6 | 2 | 0 | 8 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001091949.1 | 7 | MANE Select | |
| Ensembl | ENSP00000259951.6 | 7 | MANE Select | |
| RefSeq | NP_001091948.1 | 6 | Standard | |
| RefSeq | NP_061823.2 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antigen processing and presentation - Homo sapiens (human)
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Type I diabetes mellitus - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Allograft rejection - Homo sapiens (human)
Biological Process
- positive regulation of T cell mediated cytotoxicity
- antigen processing and presentation of peptide antigen via MHC class I
- antigen processing and presentation of endogenous peptide antigen via MHC class Ib
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
Molecular Function
- signaling receptor binding
- protein binding
- peptide antigen binding
- TAP1 binding
- TAP2 binding
Cellular Component
- Golgi membrane
- extracellular space
- endoplasmic reticulum
- plasma membrane
- external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000259951
- Coding exons
- 7
- Length
- 15754
- Individuals with no LoFs
- 125597
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 151
- Defined
- 125748
- p
- 0.000601
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 207 | 257 | 0.806 | 0.0000137 | 2847 |
| Missense (PolyPhen) | 73 | 93.332 | 0.78216 | 1014 | ||
| Synonymous | 0.369 | 101 | 106 | 0.954 | 0.00000592 | 886 |
| Loss of Function | 1.78 | 10 | 18.2 | 0.550 | 7.91e-7 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00037 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0068 | 0.0068 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000091 | 0.000088 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the presentation of foreign antigens to the immune system.;
Intolerance Scores
- LoFtool
- 0.947
- RVIS EVS
- 1.39
- RVIS percentile EVS
- 94.67
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.803
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |