TISIDB

Summary
Symbol	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
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 Cytoplasm, cytoskeleton Note=Associated with the cytoskeleton.
Domain	PF00650 CRAL/TRIO domain PF00041 Fibronectin type III domain PF07679 Immunoglobulin I-set domain PF00169 PH domain PF00069 Protein kinase domain PF00621 RhoGEF domain PF00435 Spectrin repeat
Function	Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0001662 behavioral fear response GO:0002209 behavioral defense response GO:0007009 plasma membrane organization GO:0007265 Ras protein signal transduction GO:0007266 Rho protein signal transduction GO:0007270 neuron-neuron synaptic transmission GO:0007611 learning or memory GO:0007613 memory GO:0010720 positive regulation of cell development GO:0010769 regulation of cell morphogenesis involved in differentiation GO:0010770 positive regulation of cell morphogenesis involved in differentiation GO:0010975 regulation of neuron projection development GO:0010976 positive regulation of neuron projection development GO:0016358 dendrite development GO:0022604 regulation of cell morphogenesis GO:0030534 adult behavior GO:0031346 positive regulation of cell projection organization GO:0033555 multicellular organismal response to stress GO:0035023 regulation of Rho protein signal transduction GO:0035176 social behavior GO:0035249 synaptic transmission, glutamatergic GO:0042220 response to cocaine GO:0042596 fear response GO:0043279 response to alkaloid GO:0044708 single-organism behavior GO:0045666 positive regulation of neuron differentiation GO:0046578 regulation of Ras protein signal transduction GO:0048013 ephrin receptor signaling pathway GO:0048148 behavioral response to cocaine GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048813 dendrite morphogenesis GO:0048814 regulation of dendrite morphogenesis GO:0050769 positive regulation of neurogenesis GO:0050773 regulation of dendrite development GO:0050775 positive regulation of dendrite morphogenesis GO:0050804 modulation of synaptic transmission GO:0050890 cognition GO:0051056 regulation of small GTPase mediated signal transduction GO:0051703 intraspecies interaction between organisms GO:0051705 multi-organism behavior GO:0051962 positive regulation of nervous system development GO:0051966 regulation of synaptic transmission, glutamatergic GO:0060996 dendritic spine development GO:0060997 dendritic spine morphogenesis GO:0060998 regulation of dendritic spine development GO:0060999 positive regulation of dendritic spine development GO:0061001 regulation of dendritic spine morphogenesis GO:0061003 positive regulation of dendritic spine morphogenesis GO:0072657 protein localization to membrane GO:0072659 protein localization to plasma membrane GO:0097061 dendritic spine organization GO:1900006 positive regulation of dendrite development GO:1903076 regulation of protein localization to plasma membrane GO:1903729 regulation of plasma membrane organization GO:1904375 regulation of protein localization to cell periphery GO:1990778 protein localization to cell periphery
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0005089 Rho guanyl-nucleotide exchange factor activity GO:0005096 GTPase activator activity GO:0008047 enzyme activator activity GO:0030695 GTPase regulator activity GO:0060589 nucleoside-triphosphatase regulator activity
Cellular Component	GO:0015629 actin cytoskeleton

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-422475: Axon guidance R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE R-HSA-1266738: Developmental Biology R-HSA-2682334: EPH-Ephrin signaling R-HSA-3928662: EPHB-mediated forward signaling R-HSA-416482: G alpha (12/13) signalling events R-HSA-416476: G alpha (q) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-5683057: MAPK family signaling cascades R-HSA-5687128: MAPK6/MAPK4 signaling R-HSA-193648: NRAGE signals death through JNK R-HSA-194840: Rho GTPase cycle R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-194315: Signaling by Rho GTPases R-HSA-166520: Signalling by NGF R-HSA-193704: p75 NTR receptor-mediated signalling

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-422475: Axon guidance
R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE
R-HSA-1266738: Developmental Biology
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928662: EPHB-mediated forward signaling
R-HSA-416482: G alpha (12/13) signalling events
R-HSA-416476: G alpha (q) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5687128: MAPK6/MAPK4 signaling
R-HSA-193648: NRAGE signals death through JNK
R-HSA-194840: Rho GTPase cycle
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-194315: Signaling by Rho GTPases
R-HSA-166520: Signalling by NGF
R-HSA-193704: p75 NTR receptor-mediated signalling

Summary
Symbol	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KALRN 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	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
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 KALRN 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	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
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 KALRN 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	0.048	0.896
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.136	0.848
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.181	0.759
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.217	0.508
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.317	0.886
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.088	0.976
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.308	0.507
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.371	0.756
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.324	0.791
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.59	0.516
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	1.508	0.216
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.004	0.979

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KALRN 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	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
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	25.9	8.2	17.7	0.0389
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	25.9	8.5	17.4	0.0441
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	47.6	11.8	35.8	0.0336
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	50	0	50	0.0849
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	46.2	18.2	28	0.211
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	33.3	12.5	20.8	0.312
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	40	0	40	0.11
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	28.6	-3.6	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	18.4	3.7	14.7	0.126
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	27.3	7.7	19.6	0.22
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KALRN. 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	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KALRN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KALRN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KALRN. 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	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KALRN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KALRN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KALRN
Name	kalirin, RhoGEF kinase
Aliases	duo; Hs.8004; DUET; Kalirin; ARHGEF24; serine/threonine kinase with Dbl and pleckstrin homology domains; hun ......
Chromosomal Location	3q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KALRN collected from DrugBank database.

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

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