TISIDB

Summary
Symbol	HLA-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
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
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:0033218 amide binding GO:0042277 peptide binding GO:0042605 peptide antigen binding GO:0046977 TAP binding GO:0046978 TAP1 binding GO:0046979 TAP2 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
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

> KEGG and Reactome Pathway

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KEGG

hsa04144 Endocytosis
hsa04145 Phagosome
hsa04514 Cell adhesion molecules (CAMs)
hsa04612 Antigen processing and presentation

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
Symbol	HLA-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HLA-F 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-F and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
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.

Summary
Symbol	HLA-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
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-F 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	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.54	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-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
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-F 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	0.657	0.227
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.488	0.753
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.785	0.495
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.281	0.57
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.795	0.764
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.37	0.911
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.44	0.427
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.039	0.53
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.333	0.867
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.374	0.577
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	1.275	0.738
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.115	0.504

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HLA-F 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	1.4	2.3	0.469
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	1.7	2	0.532
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	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	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-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
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-F. 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-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
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-F. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HLA-F. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HLA-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
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-F. 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-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HLA-F expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HLA-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HLA-F and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HLA-F
Name	major histocompatibility complex, class I, F
Aliases	HLA-5.4; HLAF; HLA F antigen; MHC class I antigen F; MHC class Ib antigen; leukocyte antigen F; HLA class I ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HLA-F collected from DrugBank database.

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

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