TISIDB

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
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; Peripheral membrane protein.
Domain	PF06311 NUMB domain PF00640 Phosphotyrosine interaction domain (PTB/PID)
Function	Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage.

> Gene Ontology [ TOP ]
Biological Process	GO:0001738 morphogenesis of a polarized epithelium GO:0007009 plasma membrane organization GO:0007219 Notch signaling pathway GO:0007405 neuroblast proliferation GO:0007409 axonogenesis GO:0008593 regulation of Notch signaling pathway GO:0010720 positive regulation of cell development GO:0017145 stem cell division GO:0021537 telencephalon development GO:0021591 ventricular system development GO:0021670 lateral ventricle development GO:0021846 cell proliferation in forebrain GO:0021849 neuroblast division in subventricular zone GO:0021872 forebrain generation of neurons GO:0021873 forebrain neuroblast division GO:0030323 respiratory tube development GO:0030324 lung development GO:0030335 positive regulation of cell migration GO:0030856 regulation of epithelial cell differentiation GO:0030858 positive regulation of epithelial cell differentiation GO:0030859 polarized epithelial cell differentiation GO:0030860 regulation of polarized epithelial cell differentiation GO:0030862 positive regulation of polarized epithelial cell differentiation GO:0030900 forebrain development GO:0034330 cell junction organization GO:0034332 adherens junction organization GO:0036445 neuronal stem cell division GO:0040017 positive regulation of locomotion GO:0045216 cell-cell junction organization GO:0045746 negative regulation of Notch signaling pathway GO:0048103 somatic stem cell division GO:0048667 cell morphogenesis involved in neuron differentiation GO:0050769 positive regulation of neurogenesis GO:0051272 positive regulation of cellular component movement GO:0051962 positive regulation of nervous system development GO:0055057 neuroblast division GO:0060428 lung epithelium development GO:0060479 lung cell differentiation GO:0060487 lung epithelial cell differentiation GO:0060541 respiratory system development GO:0061351 neural precursor cell proliferation GO:0061564 axon development GO:0072089 stem cell proliferation GO:0072657 protein localization to membrane GO:0072659 protein localization to plasma membrane GO:1903076 regulation of protein localization to plasma membrane GO:1903077 negative regulation of protein localization to plasma membrane GO:1903729 regulation of plasma membrane organization GO:1903828 negative regulation of cellular protein localization GO:1904375 regulation of protein localization to cell periphery GO:1904376 negative regulation of protein localization to cell periphery GO:1905330 regulation of morphogenesis of an epithelium GO:1905332 positive regulation of morphogenesis of an epithelium GO:1990778 protein localization to cell periphery GO:2000027 regulation of organ morphogenesis GO:2000147 positive regulation of cell motility
Molecular Function	GO:0008013 beta-catenin binding GO:0045294 alpha-catenin binding GO:0045296 cadherin binding GO:0050839 cell adhesion molecule binding GO:0098631 protein binding involved in cell adhesion GO:0098632 protein binding involved in cell-cell adhesion GO:0098641 cadherin binding involved in cell-cell adhesion
Cellular Component	GO:0005769 early endosome GO:0005913 cell-cell adherens junction GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0016323 basolateral plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0030055 cell-substrate junction GO:0030135 coated vesicle GO:0030136 clathrin-coated vesicle GO:0045177 apical part of cell

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04330 Notch signaling pathway
Reactome	R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-422475: Axon guidance R-HSA-5610780: Degradation of GLI1 by the proteasome R-HSA-1266738: Developmental Biology R-HSA-5610787: Hedgehog 'off' state R-HSA-5632684: Hedgehog 'on' state R-HSA-373760: L1CAM interactions R-HSA-437239: Recycling pathway of L1 R-HSA-162582: Signal Transduction R-HSA-5358351: Signaling by Hedgehog R-HSA-157118: Signaling by NOTCH R-HSA-1980143: Signaling by NOTCH1

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04330 Notch signaling pathway

Reactome

R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-422475: Axon guidance
R-HSA-5610780: Degradation of GLI1 by the proteasome
R-HSA-1266738: Developmental Biology
R-HSA-5610787: Hedgehog 'off' state
R-HSA-5632684: Hedgehog 'on' state
R-HSA-373760: L1CAM interactions
R-HSA-437239: Recycling pathway of L1
R-HSA-162582: Signal Transduction
R-HSA-5358351: Signaling by Hedgehog
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NUMB 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 ]

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

PMID	Cancer type	Relation to immunity	Evidence sentences
26523864	Ovarian Carcinoma	Inhibit immunity (T cell function)	EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling.

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
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 NUMB 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	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
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 NUMB 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	-0.093	0.744
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.109	0.958
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.234	0.869
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.441	0.233
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.169	0.94
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.793	0.795
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.053	0.896
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.089	0.959
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.235	0.905
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.26	0.864
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	0.885	0.692
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.109	0.0181

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of NUMB 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	0	3.7	0.27
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	0	3.7	0.314
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	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NUMB. 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	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NUMB. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NUMB. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NUMB. 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	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NUMB expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NUMB and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NUMB
Name	numb homolog (Drosophila)
Aliases	C14orf41; numb (Drosophila) homolog; chromosome 14 open reading frame 41; S171; c14_5527; h-Numb; Protein S1 ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NUMB collected from DrugBank database.

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

Browse NUMB