TISIDB

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
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	Cell surface Cytoplasm
Domain	PF15908 Hyaluronan mediated motility receptor C-terminal PF15905 Hyaluronan mediated motility receptor N-terminal
Function	Receptor for hyaluronic acid (HA) (By similarity). Involved in cell motility (By similarity). When hyaluronan binds to HMMR, the phosphorylation of a number of proteins, including PTK2/FAK1 occurs. May also be involved in cellular transformation and metastasis formation, and in regulating extracellular-regulated kinase (ERK) activity. May act as a regulator of adipogenisis (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000086 G2/M transition of mitotic cell cycle GO:0006022 aminoglycan metabolic process GO:0006026 aminoglycan catabolic process GO:0006027 glycosaminoglycan catabolic process GO:0030203 glycosaminoglycan metabolic process GO:0030212 hyaluronan metabolic process GO:0030214 hyaluronan catabolic process GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044839 cell cycle G2/M phase transition GO:1901136 carbohydrate derivative catabolic process GO:1901565 organonitrogen compound catabolic process GO:1903510 mucopolysaccharide metabolic process
Molecular Function	GO:0005539 glycosaminoglycan binding GO:0005540 hyaluronic acid binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04512 ECM-receptor interaction
Reactome	R-HSA-8854518: AURKA Activation by TPX2 R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-69275: G2/M Transition R-HSA-1630316: Glycosaminoglycan metabolism R-HSA-2142845: Hyaluronan metabolism R-HSA-2160916: Hyaluronan uptake and degradation R-HSA-1430728: Metabolism R-HSA-71387: Metabolism of carbohydrates R-HSA-453274: Mitotic G2-G2/M phases

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HMMR 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 HMMR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18323802	Chronic Lymphocytic Leukemia	Promote immunity (T cell function); essential for immunotherapy	A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination.
19092852	Chronic Lymphocytic Leukemia	Inhibit immunity	CLL cases with a higher RHAMM expression showed a significantly shorter median treatment-free survival. Among patients with mutated immunoglobulin heavy chain genes, an analysis of RHAMM expression enabled to distinguish subgroup of patients with favorable prognosis. In lymph nodes, RHAMM staining correlated with a higher Ki-67 index and CD40L expression. Functionally, stimulation with CD40L enhanced RHAMM expression in CLL.
20083664	Acute Myeloid Leukemia; Myeloma	Promote immunity	These patients showed an increase of CD8(+)RHAMM-R3_tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells and an increase of R3-specific CD8+ T cells. Two of these patients showed a significant decrease of regulatory T cells (Tregs). High-dose RHAMM-R3 peptide vaccination induced immunological responses and positive clinical effects. Therefore, RHAMM constitutes a promising structure for further targeted immunotherapies in patients with different hematologic malignancies.
20220777	Chronic Lymphocytic Leukemia	Immunotherapy target	CD8(+) T cells primed with the RHAMM-derived epitope R3, which is restricted by human leukocyte antigen (HLA)-A2, effectively lyse RHAMM(+) CLL cells. Thus peptide vaccination in six CLL patients was safe and could elicit to some extent specific CD8(+) T-cell responses against the tumor antigen RHAMM.
16931630	leukemia	Promote immunity	Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control.

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
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 HMMR 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	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
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 HMMR 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	-0.162	0.624
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.02	0.986
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.296	0.748
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.069	0.869
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.291	0.797
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.528	0.713
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.009	0.981
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.362	0.781
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.481	0.714
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.736	0.445
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	-0.945	0.488
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.397	0.00235

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HMMR 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	7.4	1.4	6	0.177
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	7.4	1.7	5.7	0.231
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	4.5	0	4.5	1
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	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HMMR. 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	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HMMR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HMMR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HMMR. 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	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HMMR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HMMR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HMMR
Name	hyaluronan-mediated motility receptor (RHAMM)
Aliases	RHAMM; CD168; IHABP; intracellular hyaluronic acid-binding protein; receptor for hyaluronan-mediated motilit ......
Chromosomal Location	5q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HMMR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting HMMR.

ID	Name	Drug Type	Targets	#Targets
DB08818	Hyaluronic acid	Small Molecule	C1QBP, CD44, HABP2, HABP4, HAPLN1, HAPLN3, HAPLN4, HMMR, ICAM1, IM ......	15

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