TISIDB

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
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 [ TOP ]
Subcellular Location	Membrane; Single-pass type I membrane protein.
Domain	PF07654 Immunoglobulin C1-set domain PF00129 Class I Histocompatibility antigen PF06623 MHC_I C-terminus
Function	Involved in the presentation of foreign antigens to the immune system.

> Gene Ontology [ TOP ]
Biological Process	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:0019882 antigen processing and presentation GO:0019884 antigen processing and presentation of exogenous antigen GO:0034340 response to type I interferon GO:0034341 response to interferon-gamma GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I GO:0048002 antigen processing and presentation of peptide antigen GO:0060333 interferon-gamma-mediated signaling pathway GO:0060337 type I interferon signaling pathway GO:0071346 cellular response to interferon-gamma GO:0071357 cellular response to type I interferon
Molecular Function	GO:0003823 antigen binding GO:0030881 beta-2-microglobulin binding GO:0033218 amide binding GO:0042277 peptide binding GO:0042605 peptide 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 [ TOP ]
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-1643685: Disease R-HSA-1236974: ER-Phagosome pathway R-HSA-1236977: Endosomal/Vacuolar pathway R-HSA-162906: HIV Infection R-HSA-162909: Host Interactions of HIV factors R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling R-HSA-877300: Interferon gamma signaling R-HSA-164940: Nef mediated downregulation of MHC class I complex cell surface expression R-HSA-164938: Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters R-HSA-6798695: Neutrophil degranulation R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis

> KEGG and Reactome Pathway

[ TOP ]

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-1643685: Disease
R-HSA-1236974: ER-Phagosome pathway
R-HSA-1236977: Endosomal/Vacuolar pathway
R-HSA-162906: HIV Infection
R-HSA-162909: Host Interactions of HIV factors
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-164940: Nef mediated downregulation of MHC class I complex cell surface expression
R-HSA-164938: Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-6798695: Neutrophil degranulation
R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HLA-A 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

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Literatures describing the relation between HLA-A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26381407	Melanoma	Promote immunity	This treatment combined with tapasin reconstitution and IFN-γ stimulation restored the highest level of HLA class I expression and its ability to elicit cytotoxic T cell responses.
25294906	Thyroid Gland Papillary Carcinoma	Promote immunity (infiltration)	Both MHC class I and β2-microglobulin expression was reduced or absent in 76% of PTC specimens and was associated with reduced tumor-infiltrating immune cells, including effector (CD3(+), CD8(+), CD16(+)) and suppressor (FoxP3(+)) populations.
10699951	Uveal melanoma	Promote immunity	In OMM-1 cells, IFN-alpha and -gamma increased the expression of HLA-A but did not induce expression of the 2 B alleles, indicating an HLA-B locus-specific loss. The lack of HLA expression may explain why uveal melanoma cells escape immune surveillance by cytotoxic T cells and complicate the development of immunotherapy in uveal melanoma.
18268541	Neuroblastoma	Promote immunity (T and NK cell function)	This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells.
28783722	Melanoma	Promote immunity (T cell function); essential for immunotherapy	On the basis of our initial optimization of the 2CT-CRISPR assay, we expected that genes directly associated with MHC class I antigen processing and presentation would be enriched in our screens, and found that HLA-A, B2M, TAP1, TAP2, and TAPBP were among the most highly-enriched genes in our screen
28783722	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Loss of expression of these 19 genes within tumours could diminish or extinguish the presentation of tumour antigens (including HLA-A, HLA-F, B2M, TAP1 and TAP2); T cell co- stimulation (ICAM1, CLECL1, LILRA1 and LILRA3); or cytokine production and signalling (JAK2 and STAT1) in the tumour microenvironment that drive infiltration and activation of T cells, and thus serve as a principal mechanism in immune evasion.
23400852	Neuroblastoma	Promote immunity (T cell function)	Corresponding to this upregulation, T cell activity and cytoxicity was enhanced in the presence of SY5Y-TrkA cells or by medium conditioned by them, suggesting the existence of additional soluble factors stimulating the T cell response. Activation of natural killer (NK) cells was only increased in the presence of SY5Y-TrkA conditioned medium (CM) and not in co-culture assays, suggesting a dominant inhibitory effect of upregulated MHC class I as the primary NK cell escape mechanism of TrkA-expressing neuroblastomas.
23807163	Ovarian carcinoma	Promote immunity (T cell function)	We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody.
22392913	Melanoma; Breast Carcinoma	Promote immunity (T cell function); essential for immunotherapy	Laser illumination also slightly but significantly enhanced the expression of costimulatory molecule CD80 and MHC I on inoculated DCs. As a result, more vigorous expansion of tumor-specific IFN-γ(+)CD8(+) T lymphocytes and enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in the laser-treated group over the control group.
29423109	Lung Carcinoma	Promote immunity (T cell function)	All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells.
29496759	Melanoma	Promote immunity	In addition, significantly decreased levels of IFNγ were secreted from TILs incubated with MEX3B-overexpressing tumor cells. Interestingly, this phenotype was rescued upon overexpression of exogenous HLA-A2.
21918960	cervical squamous cell carcinoma	Promote immunity	E7(61-69) (CDSTLRLCV) and E7(67-76) (LCVQSTHVDI) induced significantly greater IFN-γ production as well as increased in vitro cytotoxicity against SiHa cells compared with those of other peptides and the negative control (P < .01), and the antitumor effects of these peptide-sensitized PBMCs were induced by CD8(+) CTLs.
21908738	Myeloma	Promote immunity	MHC class I expression on myeloma cells and contact with T cells were required for CD8(+) T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-gamma and/or perforin compared with single-positive CD8(+) T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones.

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
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

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Statistical results of HLA-A in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: 3.53; FDR: 0.000150	Sensitive to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 2.2	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
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

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Points in the above scatter plot represent the expression difference of HLA-A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	1.297	0.171
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.769	0.608
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.994	0.623
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.557	0.302
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.769	0.809
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.286	0.942
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.308	0.646
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.564	0.837
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.102	0.975
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.028	0.783
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.609	0.916
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.046	0.734

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HLA-A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
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-A. 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 [ TOP ]

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HLA-A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HLA-A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HLA-A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HLA-A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HLA-A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HLA-A
Name	major histocompatibility complex, class I, A
Aliases	HLAA; MHC class I antigen HLA-A heavy chain; antigen presenting molecule; leukocyte antigen class I-A; MHC c ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HLA-A collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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