TISIDB

Summary
Symbol	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
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	Isoform 1: Nucleus, nucleolus. Note=Also shows a granular distribution in the cytoplasm.; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm Note=Weak expression in the nucleus.
Domain	PF15316 MyoD family inhibitor
Function	Acts as a transcriptional activator or repressor. Inhibits the transcriptional activation of Zic family proteins ZIC1, ZIC2 and ZIC3. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the cytoplasm. Modulates the expression from both cellular and viral promoters. Down-regulates Tat-dependent transcription of the human immunodeficiency virus type 1 (HIV-1) LTR by interacting with HIV-1 Tat and Rev and impairing their nuclear import, probably by rendering the NLS domains inaccessible to importin-beta. Also stimulates activation of human T-cell leukemia virus type I (HTLV-I) LTR. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin regulation of the WNT and JNK signaling pathways.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0006606 protein import into nucleus GO:0006913 nucleocytoplasmic transport GO:0007254 JNK cascade GO:0007257 activation of JUN kinase activity GO:0016055 Wnt signaling pathway GO:0017038 protein import GO:0019058 viral life cycle GO:0019080 viral gene expression GO:0019083 viral transcription GO:0030111 regulation of Wnt signaling pathway GO:0031098 stress-activated protein kinase signaling cascade GO:0032147 activation of protein kinase activity GO:0032386 regulation of intracellular transport GO:0032387 negative regulation of intracellular transport GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0033157 regulation of intracellular protein transport GO:0033674 positive regulation of kinase activity GO:0034504 protein localization to nucleus GO:0042306 regulation of protein import into nucleus GO:0042308 negative regulation of protein import into nucleus GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043506 regulation of JUN kinase activity GO:0043507 positive regulation of JUN kinase activity GO:0043900 regulation of multi-organism process GO:0043902 positive regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044033 multi-organism metabolic process GO:0044744 protein targeting to nucleus GO:0045860 positive regulation of protein kinase activity GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0046782 regulation of viral transcription GO:0046822 regulation of nucleocytoplasmic transport GO:0046823 negative regulation of nucleocytoplasmic transport GO:0048524 positive regulation of viral process GO:0050434 positive regulation of viral transcription GO:0050792 regulation of viral process GO:0051051 negative regulation of transport GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051224 negative regulation of protein transport GO:0051403 stress-activated MAPK cascade GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090317 negative regulation of intracellular protein transport GO:0198738 cell-cell signaling by wnt GO:1900180 regulation of protein localization to nucleus GO:1900181 negative regulation of protein localization to nucleus GO:1902593 single-organism nuclear import GO:1903533 regulation of protein targeting GO:1903828 negative regulation of cellular protein localization GO:1903900 regulation of viral life cycle GO:1903902 positive regulation of viral life cycle GO:1904589 regulation of protein import GO:1904590 negative regulation of protein import GO:1904950 negative regulation of establishment of protein localization
Molecular Function	GO:0008134 transcription factor binding GO:0030332 cyclin binding GO:0030957 Tat protein binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MDFIC 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	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
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

[ TOP ]

Statistical results of MDFIC 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: 4	Resistant to T-cell proliferation

Summary
Symbol	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
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 MDFIC 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	-0.555	0.141
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.464	0.81
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.618	0.654
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.194	0.517
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.183	0.907
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.213	0.919
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.187	0.711
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.05	0.978
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.465	0.815
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.488	0.685
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	0.765	0.687
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.025	0.791

> Mutation difference between responders and non-responders

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

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% 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	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	7.1	-7.1	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	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
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	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MDFIC. 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	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MDFIC. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MDFIC. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MDFIC. 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	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MDFIC expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MDFIC and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MDFIC
Name	MyoD family inhibitor domain containing
Aliases	HIC; I-mfa domain-containing protein; MyoD family inhibitor domain-containing protein
Chromosomal Location	7q31.1-q31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MDFIC collected from DrugBank database.

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

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