TISIDB

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
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
Domain	PF13460 NAD(P)H-binding
Function	Broad specificity oxidoreductase that catalyzes the NADPH-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to heme catabolism and metabolizes linear tetrapyrroles. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin.

> Gene Ontology [ TOP ]
Biological Process	GO:0006778 porphyrin-containing compound metabolic process GO:0006787 porphyrin-containing compound catabolic process GO:0019439 aromatic compound catabolic process GO:0033013 tetrapyrrole metabolic process GO:0033015 tetrapyrrole catabolic process GO:0042167 heme catabolic process GO:0042168 heme metabolic process GO:0042440 pigment metabolic process GO:0044270 cellular nitrogen compound catabolic process GO:0046149 pigment catabolic process GO:0046700 heterocycle catabolic process GO:0051186 cofactor metabolic process GO:0051187 cofactor catabolic process GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process
Molecular Function	GO:0004074 biliverdin reductase activity GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor GO:0016645 oxidoreductase activity, acting on the CH-NH group of donors GO:0016646 oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor GO:0042602 riboflavin reductase (NADPH) activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00740 Riboflavin metabolism hsa00860 Porphyrin and chlorophyll metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-189483: Heme degradation R-HSA-1430728: Metabolism R-HSA-189445: Metabolism of porphyrins

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between BLVRB 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 ]
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Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
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 BLVRB 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	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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	Total # shRNA with >= 4-fold: 3	Resistant to T-cell proliferation

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
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 BLVRB 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	-0.01	0.978
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.254	0.933
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.171	0.937
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.484	0.362
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.049	0.976
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.164	0.589
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.191	0.649
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.191	0.89
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.386	0.827
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.122	0.957
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	-0.308	0.932
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.022	0.842

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of BLVRB in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of BLVRB. 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	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of BLVRB. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by BLVRB. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of BLVRB. 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	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of BLVRB expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between BLVRB and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	BLVRB
Name	biliverdin reductase B
Aliases	SDR43U1; short chain dehydrogenase/reductase family 43U, member 1; (flavin reductase (NADPH)); FLR; Flavin r ......
Chromosomal Location	19q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting BLVRB collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting BLVRB.

ID	Name	Drug Type	Targets	#Targets
DB00140	Riboflavin	Small Molecule	BLVRB, RFK	2
DB00157	NADH	Small Molecule	AASS, ACADS, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH7, AKR1B1, AKR1C1 ......	144
DB02073	Biliverdine IX Alpha	Small Molecule	BLVRB, HMOX1, MB	3
DB03247	Flavin mononucleotide	Small Molecule	BLVRB, DHODH, DPYD, HAO1, HAO2, NOS1, PNPO, POR, PPCDC, RFK, RPS6K ......	12
DB03461	2'-Monophosphoadenosine 5'-Diphosphoribose	Small Molecule	ADH1B, AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, BLVRB, CRY ......	28
DB04345	7,8-dimethylalloxazine	Small Molecule	BLVRB	1
DB04363	Mesobiliverdin Iv Alpha	Small Molecule	BLVRB	1

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