HLA-E
protein-codingmajor histocompatibility complex, class I, E, the group of Histocompatibility complex|C1-set domain containing
Gene summary
HLA-E belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. [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 ~4.7 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-E variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005516.6. 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 | 0 | |||||
| missense | 2 | 1 | 3 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 5 | 1 | 0 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005507.3 | 7 | MANE Select | |
| Ensembl | ENSP00000365817.4 | 7 | MANE Select | |
| Ensembl | ENSP00000566696.1 | 7 | Standard | |
| Ensembl | ENSP00000566697.1 | 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 antibody-dependent cellular cytotoxicity
- positive regulation of T cell mediated cytotoxicity
- adaptive immune response
- antigen processing and presentation of peptide antigen via MHC class I
- antigen processing and presentation of endogenous peptide antigen via MHC class Ib
Molecular Function
- signaling receptor binding
- protein binding
- beta-2-microglobulin binding
- MHC class I protein binding
- peptide antigen binding
Cellular Component
- Golgi membrane
- extracellular space
- plasma membrane
- external side of plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376630
- Coding exons
- 7
- Length
- 4739
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125743
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.98 | 132 | 213 | 0.619 | 0.0000107 | 2306 |
| Missense (PolyPhen) | 48 | 99.076 | 0.48448 | 1067 | ||
| Synonymous | 1.58 | 76 | 95.6 | 0.795 | 0.00000555 | 731 |
| Loss of Function | 2.80 | 6 | 19.3 | 0.311 | 8.34e-7 | 207 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000066 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000056 | 0.000053 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules.;
Intolerance Scores
- LoFtool
- 0.533
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.721
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |