Browse HLA-G

Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 1: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Isoform 2: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Isoform 3: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Isoform 4: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Isoform 5: Secreted ; SUBCELLULAR LOCATION: Isoform 6: Secreted ; SUBCELLULAR LOCATION: Isoform 7: Secreted
Domain PF07654 Immunoglobulin C1-set domain
PF00129 Class I Histocompatibility antigen
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.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
GO:0002478 antigen processing and presentation of exogenous peptide antigen
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
GO:0002480 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
GO:0002507 tolerance induction
GO:0002517 T cell tolerance induction
GO:0002521 leukocyte differentiation
GO:0002643 regulation of tolerance induction
GO:0002645 positive regulation of tolerance induction
GO:0002664 regulation of T cell tolerance induction
GO:0002666 positive regulation of T cell tolerance induction
GO:0002683 negative regulation of immune system process
GO:0002694 regulation of leukocyte activation
GO:0002695 negative regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002764 immune response-regulating signaling pathway
GO:0002765 immune response-inhibiting signal transduction
GO:0002767 immune response-inhibiting cell surface receptor signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006968 cellular defense response
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0019882 antigen processing and presentation
GO:0019884 antigen processing and presentation of exogenous antigen
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0032615 interleukin-12 production
GO:0032655 regulation of interleukin-12 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032945 negative regulation of mononuclear cell proliferation
GO:0034340 response to type I interferon
GO:0034341 response to interferon-gamma
GO:0042098 T cell proliferation
GO:0042110 T cell activation
GO:0042129 regulation of T cell proliferation
GO:0042130 negative regulation of T cell proliferation
GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I
GO:0045066 regulatory T cell differentiation
GO:0045580 regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0045589 regulation of regulatory T cell differentiation
GO:0045591 positive regulation of regulatory T cell differentiation
GO:0045619 regulation of lymphocyte differentiation
GO:0045621 positive regulation of lymphocyte differentiation
GO:0045785 positive regulation of cell adhesion
GO:0046651 lymphocyte proliferation
GO:0048002 antigen processing and presentation of peptide antigen
GO:0050670 regulation of lymphocyte proliferation
GO:0050672 negative regulation of lymphocyte proliferation
GO:0050777 negative regulation of immune response
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050866 negative regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050868 negative regulation of T cell activation
GO:0050870 positive regulation of T cell activation
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060337 type I interferon signaling pathway
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070664 negative regulation of leukocyte proliferation
GO:0071346 cellular response to interferon-gamma
GO:0071357 cellular response to type I interferon
GO:0071593 lymphocyte aggregation
GO:0097028 dendritic cell differentiation
GO:1902105 regulation of leukocyte differentiation
GO:1902106 negative regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903038 negative regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903706 regulation of hemopoiesis
GO:1903707 negative regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:2001198 regulation of dendritic cell differentiation
GO:2001199 negative regulation of dendritic cell differentiation
Molecular Function GO:0003823 antigen binding
Cellular Component GO:0005769 early endosome
GO:0010008 endosome membrane
GO:0012507 ER to Golgi transport vesicle membrane
GO:0030133 transport vesicle
GO:0030134 ER to Golgi transport vesicle
GO:0030135 coated vesicle
GO:0030139 endocytic vesicle
GO:0030176 integral component of endoplasmic reticulum membrane
GO:0030658 transport vesicle membrane
GO:0030659 cytoplasmic vesicle membrane
GO:0030662 coated vesicle membrane
GO:0030666 endocytic vesicle membrane
GO:0030670 phagocytic vesicle membrane
GO:0031227 intrinsic component of endoplasmic reticulum membrane
GO:0031901 early endosome membrane
GO:0042611 MHC protein complex
GO:0042612 MHC class I protein complex
GO:0044440 endosomal part
GO:0045335 phagocytic vesicle
GO:0071556 integral component of lumenal side of endoplasmic reticulum membrane
GO:0098552 side of membrane
GO:0098553 lumenal side of endoplasmic reticulum membrane
> KEGG and Reactome Pathway
 
KEGG hsa04144 Endocytosis
hsa04145 Phagosome
hsa04514 Cell adhesion molecules (CAMs)
hsa04612 Antigen processing and presentation
hsa04650 Natural killer cell mediated cytotoxicity
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983170: Antigen Presentation
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1236974: ER-Phagosome pathway
R-HSA-1236977: Endosomal/Vacuolar pathway
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-877300: Interferon gamma signaling
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HLA-G and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between HLA-G and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
22678912MelanomaInhibit immunityThese data emphasize the impact of HLA-G conformation on its efficiency at inhibiting the antitumor response and thus favoring tumor progression.
18288133Chronic Lymphocytic LeukemiaInhibit immunity (NK cell function); immunotherapy targetHLA-G1 surface expression was observed in CLL and was very low or undetectable in MM. Notably, blocking of HLA-G1 with specific antibody on CLL samples increased their susceptibility to NK-mediated killing, demonstrating that HLA-G participates in protecting CLL cells from NK-mediated killing and may thus contribute to their immune escape in vivo.
28470686Pancreatic Carcinoma; Ampulla of Vater CarcinomaInhibit immunity (T cell function)Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p?=?0.002), Gal-9 (p?=?0.003), HVEM (p?=?0.001), IDO (p?=?0.049), HLA-G (p?=?0.004) and high CD8/FoxP3 TIL ratio (p?=?0.006) were associated with improved cancer-specific survival.
29464090Ewing SarcomaInhibit immunity (T cell function)We hypothesized that the non-classical, immune-inhibitory HLA-molecule HLA-G contributes to immune escape of EwS. HLA-G expression was not associated with risk-related patient variables or response to standard chemotherapy, but with significantly increased numbers of tumor-infiltrating CD3+ T cells compared to HLA-Gneg EwS biopsies. In a mouse model, EwS xenografts after adoptive therapy with tumor antigen-specific CAR T cells strongly expressed HLA-G whereas untreated control tumors were HLA-Gneg.
16045815MelanomaInhibit immunity (T/NK cell function)The non-classical HLA class I antigen HLA-G is an immune modulator which inhibits the functions of T cells, NK cells, and the Dendritic cells (DC). As a result, HLA-G expression in malignant cells may provide them with a mechanism to escape the immune surveillance. Our data strongly suggest that HLA-G is silenced as a result of CpG hypermethylation within a 5' regulatory region encompassing 220 bp upstream of the start codon.
24362551Chronic Lymphocytic LeukemiaInhibit immunityIn line with its role in immunomodulation, the percentage of regulatory T lymphocytes is higher in del/del patients than in patients with the other genotypes and correlates with the amounts of surface or soluble HLA-G. Furthermore, addition of sHLA-G-rich plasma from patients with chronic lymphocytic leukemia induces natural killer cell apoptosis and impairs natural killer cell lysis, with effects proportional to the amount of soluble HLA-G added. Lastly, the presence of an HLA-G 14 base pair polymorphism is of prognostic value, with del/del patients showing reduced overall survival, as compared to those with other genotypes. These results suggest that: (i) the HLA-G 14 base pair polymorphism influences the levels of surface and soluble HLA-G expression, and (ii) the over-expression of HLA-G molecules contributes to creating tolerogenic conditions.
17616704NeuroblastomaInhibit immunityHuman neuroblastoma cells trigger an immunosuppressive program in monocytes by stimulating soluble HLA-G release. Neuroblastoma patient sera selected according to high sHLA-G concentrations inhibited natural killer (NK) cell and CTL-mediated neuroblastoma cell lysis. Such lysis was partially restored by serum depletion of sHLA-G.
25228695Pan-CancerInhibit immunity (NK/T cell function)miR-152 regulates HLA-G and HLA-C, which act inhibitory to NK and T cells, thereby altering the immunogenicity of tumors. Because HLA-G and HLA-C are both ligands for inhibitory NK cell receptors (9, 10), the miR-148 family is an important regulator of an effective immune response against tumor cells and also against viral infections.
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of HLA-G in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of HLA-G in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.3310.567
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.8760.344
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.080.925
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-1.3830.0725
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.3280.26
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-1.4590.3
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.430.326
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8740.445
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1170.93
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.1360.934
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.210.921
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.3960.144
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HLA-G in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.44.13.30.61
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.45.12.30.647
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HLA-G. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HLA-G. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HLA-G.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HLA-G. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HLA-G expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HLA-G and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHLA-G
Namemajor histocompatibility complex, class I, G
Aliases b2 microglobulin; HLA-G histocompatibility antigen, class I, G; MHC-G; HLA G antigen; MHC class I antigen G; ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HLA-G collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.