HLA-G
protein-codingmajor histocompatibility complex, class I, G, the group of Histocompatibility complex|C1-set domain containing
Gene summary
HLA-G 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-G is expressed on fetal derived placental cells. 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 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes 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 ~4.2 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-G variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001384290.1. 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 | 4 | 2 | 6 | |||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 4 | 2 | 7 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001371219.1 | 6 | MANE Select | |
| Ensembl | ENSP00000353472.6 | 6 | MANE Select | |
| RefSeq | NP_001350496.1 | 7 | Standard | |
| RefSeq | NP_001371209.1 | 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
- negative regulation of T cell mediated cytotoxicity
- positive regulation of T cell mediated cytotoxicity
- peripheral B cell tolerance induction
- 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
- peptide antigen binding
- CD8 receptor binding
- identical protein binding
Cellular Component
- Golgi membrane
- extracellular region
- extracellular space
- early endosome
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000428701
- Coding exons
- 6
- Length
- 4159
- Individuals with no LoFs
- 121440
- Homozygous LoFs
- 68
- Heterozygous LoFs
- 4240
- Defined
- 125748
- p
- 0.0173
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.230 | 198 | 207 | 0.955 | 0.0000112 | 2163 |
| Missense (PolyPhen) | 96 | 95.449 | 1.0058 | 1084 | ||
| Synonymous | -0.520 | 95 | 88.8 | 1.07 | 0.00000534 | 672 |
| Loss of Function | 0.105 | 17 | 17.5 | 0.973 | 7.59e-7 | 183 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.071 | 0.067 | notable |
| Latino/Admixed American | 0.015 | 0.015 | notable |
| Ashkenazi Jewish | 0.024 | 0.024 | notable |
| East Asian | 0.020 | 0.019 | notable |
| Finnish | 0.0027 | 0.0027 | notable |
| European (Non-Finnish) | 0.014 | 0.014 | notable |
| South Asian | 0.014 | 0.014 | notable |
| Other | 0.020 | 0.020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells.;
Intolerance Scores
- LoFtool
- 0.834
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.439
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |