TISIDB

Summary
Symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
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	Cytoplasm Nucleus Note=Predominantly cytoplasmic.
Domain	PF13532 2OG-Fe(II) oxygenase superfamily PF09004 Domain of unknown function (DUF1891) PF08241 Methyltransferase domain
Function	Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182).

> Gene Ontology [ TOP ]
Biological Process	GO:0001510 RNA methylation GO:0002097 tRNA wobble base modification GO:0002098 tRNA wobble uridine modification GO:0006399 tRNA metabolic process GO:0006400 tRNA modification GO:0008033 tRNA processing GO:0009451 RNA modification GO:0030488 tRNA methylation GO:0032259 methylation GO:0034470 ncRNA processing GO:0043414 macromolecule methylation
Molecular Function	GO:0000049 tRNA binding GO:0005506 iron ion binding GO:0008168 methyltransferase activity GO:0008173 RNA methyltransferase activity GO:0008175 tRNA methyltransferase activity GO:0008198 ferrous iron binding GO:0016300 tRNA (uracil) methyltransferase activity GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016706 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors GO:0016741 transferase activity, transferring one-carbon groups GO:0051213 dioxygenase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-74160: Gene Expression R-HSA-6782315: tRNA modification in the nucleus and cytosol R-HSA-72306: tRNA processing

Summary
Symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ALKBH8 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 [ TOP ]
There is no record.

Summary
Symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
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

[ TOP ]

Statistical results of ALKBH8 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: 1.06; FDR: 0.009470	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	NA/NS	NA/NS
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	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
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 ALKBH8 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	-0.132	0.617
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.323	0.7
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.006	0.992
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.029	0.926
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.124	0.928
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.085	0.956
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.045	0.863
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.202	0.856
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.135	0.913
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.032	0.966
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	0.552	0.586
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.073	0.234

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ALKBH8 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	0	1.4	-1.4	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	0	1.7	-1.7	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	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
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	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ALKBH8. 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	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ALKBH8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ALKBH8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ALKBH8. 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	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ALKBH8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ALKBH8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Aliases	MGC10235; TRM9; TRMT9; tRNA methyltransferase 9 homolog (S. cerevisiae); alkB, alkylation repair homolog 8 ( ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ALKBH8 collected from DrugBank database.

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

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