| Function |
Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface. In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins. Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal-fetal tolerance. Upon interaction with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy. Through interaction with KIR2DL4 receptor on decidual macrophages induces proinflammatory cytokine production mainly associated with tissue remodeling. Through interaction with LILRB2 receptor triggers differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance. May play a role in balancing tolerance and antiviral-immunity at maternal-fetal interface by keeping in check the effector functions of NK, CD8+ T cells and B cells. Reprograms B cells toward an immune suppressive phenotype via LILRB1. May induce immune activation/suppression via intercellular membrane transfer (trogocytosis), likely enabling interaction with KIR2DL4, which resides mostly in endosomes. Through interaction with the inhibitory receptor CD160 on endothelial cells may control angiogenesis in immune privileged sites.; Likely does not bind B2M and presents peptides. Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity.; Likely does not bind B2M and presents peptides. Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity.; Likely does not bind B2M and presents peptides. Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity.; Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface. In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins. Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal-fetal tolerance. Upon interaction with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy. Through interaction with KIR2DL4 receptor on decidual macrophages induces proinflammatory cytokine production mainly associated with tissue remodeling. Through interaction with LILRB2 receptor triggers differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance. Reprograms B cells toward an immune suppressive phenotype via LILRB1.; Likely does not bind B2M and presents peptides.; Likely does not bind B2M and presents peptides.
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| Gene References into Functions |
- HLA-G, NRP1, and PD-1, may be involved in the immune response in psoriatic patients PMID: 29790686
- Considering that others 14-bp associations were inconclusive and that other variation sites observed at HLA-G 3'UTR exhibit a proven role on post-transcriptional regulation of HLA-G expression, the complete 3'UTR segment should be analyzed in terms of disease susceptibility, instead of a single polymorphism. PMID: 30102938
- study demonstrated that HLA-G 14-bp Ins/Del polymorphism may exert no influence on susceptibility to viruses - Meta-analysis PMID: 30235670
- The findings indicate that GPER/miR148a/HLAG signaling pathway may mediates the development of ovarian endometriosis and may become a potential therapeutic target for the treatment of endometriosis. PMID: 29845209
- Significantly different distribution of HLA-G polymorphism (rs1611715), but not the serum level of sHLA-G, were found between multiple sclerosis patients and healthy individuals. PMID: 29924453
- These results indicate the importance of the HLA-G promoter SNPs in the pregnancy outcome. But to reach a more definite conclusion, subsequent studies on 3' UTR and other positions with polymorphism in the 5' UTR regions larger samples are necessary. PMID: 29797531
- HLA-G expression is associated with poor survival in stage III gastric cancer patients and represents a possible immunoescape mechanism of cancer cells. PMID: 29845360
- this study shows that HLA-G molecules have a role in predicting the newborn's likelihood for oral HPV infection at birth. PMID: 29544814
- HLA-G is highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism PMID: 29499226
- this study shows that HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients PMID: 29588183
- this study shows that HLA-G mediated immune regulation is impaired by a single amino acid exchange in the alpha 2 domain PMID: 29605689
- No significant differences in single nucleotide polymorphisms in the 3' untranslated region of HLA-G in placentas between spontaneous preterm birth and preeclampsia. PMID: 29540242
- the HLA-G 14bp ins/del gene polymorphism is an important risk factor for the incidence and poor outcome of NHL cases. PMID: 29388862
- these findings showed that HLA-G overexpression in tumor tissue correlated with poor prognosis in pancreatic adenocarcinoma PMID: 29549230
- This meta-analysis suggested that the HLA-G 14-bp insertion allele may increase the risk of recurrent implantation failure in Caucasians. PMID: 28707147
- Study shows that HLA-G alleles are skewed in autism spectrum disorder (ASD) children. HLA-G alleles seen in ASD result in immune activation. The skewing of HLA-G alleles seen in ASD might play a pathogenic role. PMID: 28923404
- these data confirm an important role of HLA-G 3'UTR polymorphisms in the development of severe forms of sepsis in Brazil PMID: 28941746
- a 14bp indel in HLA-G associated with increased flow-mediated dilatation of the brachial artery in renal transplant recipients PMID: 28987961
- the maternal HLA-G 14-bp Ins/Del polymorphism is not associated with preeclampsia risk. PMID: 29105301
- the HLA-G 14-bp Ins/Del polymorphism may be a marker for genetic susceptibility to chronic hepatitis B infection. PMID: 28929613
- The presence of the HLA-G +3142 CC genotype was associated with higher susceptibility to CMV infection after kidney transplantation. PMID: 29113092
- The results from the study suggest a possible involvement of HLA-G in the risk modulation toward hepatitis C virus infection. PMID: 28083985
- our results suggest that elevated levels of HLA- G expression, precisely sHLA- G1 homodimers, are indeed associated with persistent infection with HBV. sHLA- G (sHLA- G1 and HLA- G5 both) levels may be a prognostic indicator for spontaneous recov-ery. PMID: 28429836
- Results show that HLA-G rs1233334:CT protected against progression of endometriosis. PMID: 29234882
- The results suggest that HLA-G polymorphism has small effect on systemic lupus erythematosus susceptibility and that soluble HLA-G may be involved in the pathogenesis of the disease. PMID: 28695673
- sHLA-G levels is an independent prognosis factor and improves the prognostic stratification offered by traditional prognosticators in CRC patients. PMID: 28415627
- we found a significant association between HLA-G rs1063320 (thorn3142G>C) and 14-bp ins/del variants and risk of recurrent spontaneous abortion. PMID: 28600033
- HLA-G del/del genotypes were more frequent among mothers with gestational diabetes than in control. Babies carrying HLA-G del/del showed the highest sHLA-G levels. PMID: 28655969
- No statistically significant differences in either HLA-G allele or genotype frequencies between pre-eclampsia cases and control group have been observed. PMID: 29061057
- Overexpressed HLA-G revealed their ability to inhibit the cell proliferation and cytotoxic activity of NK-92MI cells, and reduce the secretion of IFN-gamma and TNF-alpha through immunoglobulin-like transcript 2. PMID: 29224003
- Soluble HLA-G was significantly higher in the persistent wheezing (positive modified asthma predictive index) infant group compared with the transient wheezing (negative modified asthma predictive index) group (P = 0.008). PMID: 27880031
- this study shows associations between fetal HLA-G genotype and birth weight and placental weight in a large cohort of pregnant women PMID: 28267635
- evidence is presented that HLA-G1 monomer exhibits the therapeutic effects on atopic dermatitis-like skin lesions in mice PMID: 28675838
- this study shows that HLA-G is expressed by ARPE-19 retinal pigment epithelium cells and is upregulated as a response to pro-inflammatory cytokines PMID: 28442288
- Cellular activation and pathological processes are associated with an aberrant or a neo-expression of HLA-G/soluble HLA-G. (Review) PMID: 27440734
- the +3142 C>G, but not the 14bp INS/DEL polymorphism may constitute a genetic susceptibility factor to multiple sclerosis in the Tunisian population. PMID: 27771469
- novel HLA-G-regulating miRs, miR-628-5p and miR-548q, were identified in renal cell carcinoma PMID: 27057628
- high expression of total soluble HLA-G and vesicular soluble HLA-G, together with the presence of the 14-bp deletion allele, might be involved in implantation failure PMID: 26959830
- the presented data suggest that the investigated HLA-G*0105N allele is potentially associated with recurrent spontaneous abortions through linkage disequilibrium with other genetic elements. PMID: 26754761
- these findings demonstrate the association of HLA-G polymorphism with breast cancer susceptibility in Tunisian population PMID: 26754763
- results strongly suggest the involvement of HLA-G in human African trypanosomiasis disease progression PMID: 27470243
- women with preterm premature rupture of membranes had significantly higher serum and vaginal sHLA-G concentrations compared to controls PMID: 27232355
- Serum levels of soluble HLA-G were similar in CMV- and CMV+ subjects but levels in culture supernatants were significantly higher in cells from CMV+ than from CMV- subjects stimulated with CMV antigens. The HLA-G ligand KIR2DL4 was mainly expressed on NK cells and CD56+ T cells with no differences between CMV+ and CMV- subjects. PMID: 28817184
- our study is the first to suggest that HLA-G expression may influence the clinical outcome of chronic myeloid leukemia PMID: 28841441
- SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory HLA-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides. PMID: 27443345
- HLA-G 3'UTR polymorphisms associated with a greater magnitude of HLA-G production were associated with differentiated thyroid tumours and with variables implicated in poor prognosis. PMID: 27914217
- The inhibitory properties of bronchial endothelial cellss are dysregulated in stable lung transplant recipients via TGF-beta, IL-10 and HLA-G signaling pathway. PMID: 27820781
- HLA-G expression was upregulated in chondrocyte-differentiated mesenchymal stem cells under hypoxia context and could be boosted in allogenic settings. PMID: 27465875
- this review provides new insights into the mechanisms controlling the expression and function of HLA-G at the maternal-fetal interface, and discuss their relevance for fetal tolerance PMID: 28279591
- we propose a massively parallel sequencing (NGS) with a bioinformatics strategy to evaluate the entire HLA-G regulatory and coding segments PMID: 28135606
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| Subcellular Location |
[Isoform 1]: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane. Early endosome membrane.; [Soluble HLA class I histocompatibility antigen, alpha chain G]: Secreted.; [Isoform 2]: Cell membrane; Single-pass type I membrane protein.; [Isoform 3]: Cell membrane; Single-pass type I membrane protein.; [Isoform 4]: Cell membrane; Single-pass type I membrane protein.; [Isoform 5]: Secreted. Early endosome.; [Isoform 6]: Secreted.; [Isoform 7]: Secreted.; Cell projection, filopodium membrane. |
| Protein Families |
MHC class I family |
| Tissue Specificity |
Expressed in adult eye. Expressed in immune cell subsets including monocytes, myeloid and plasmacytoid dendritic cells and regulatory T cells (Tr1)(at protein level). Secreted by follicular dendritic cell and follicular helper T cells. Isoform 5: Detected |
| Database Links |
HGNC: 4964 OMIM: 142871 KEGG: hsa:3135 STRING: 9606.ENSP00000353472 UniGene: Hs.512152 |
