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	Gene summary
	Datasets with differential expression of this gene
	Expression of this gene in the resistant group across all datasets and cell types
	Significant ligand-receptor pairs related to this gene (This gene does not contain this module)
	Known drug resistance mechanisms of this gene (This gene does not contain this module)
	MicroRNAs (miRNAs) regulating this gene
	Motifs and transcription factors (TFs) regulating this gene
	Acts as a transcription factor (This gene does not contain this module)
	Acts as a drug target< (This gene does not contain this module)

Gene: IFI6

Summary for IFI6

Gene information	Gene symbol	IFI6
	Ensembl ID	ENSG00000126709
	Entrez ID	2537
	Gene name	interferon alpha inducible protein 6
	Synonyms	6-16\|FAM14C\|G1P3\|IFI-6-16\|IFI616
	Gene type	protein_coding
	UniProtAcc	P09912

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Dataset with differentially expressed gene: IFI6

Differentially expression genes between the resistant and sensitive groups. A positive avg_log2FC represents significantly high expression in the resistant group, while a negative avg_log2FC represents significantly low expression in the resistant group.

Dataset	Source	Tissue	Cancer type level1	Cancer type level2	Drug type	Regimen	Timepoint	Cell type	avg_log2FC	p_val_adj
GSE140440	DU145 and PC cell lines	Cell line	Prostate cancer	Prostate cancer	Chemotherapy	docetaxel	NA	Malignant cells	2.10739	6.69e-12
GSE186960	Panc1 cell line	Cell line	Pancreatic cancer	Pancreatic ductal adenocarcinoma (PDAC)	Chemotherapy	gemcitabine	NA	Malignant cells	0.567446	9.99e-39
GSE138267	CDX	Tumor tissue	Lung cancer	Small cell lung cancer (SCLC)	Chemotherapy	NA	NA	Malignant cells	1.34918	0.00e+00
GSE163836	FCIBC02 cell line	Cell line	Breast cancer	Inflammatory breast cancer	Chemotherapy	paclitaxel	NA	Malignant cells	-0.504636	0.00e+00
GSE169246_PacBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	post	cDCs	-0.631561	3.47e-02
GSE169246_PacBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	post	Mono/Macro	-0.426922	0.00e+00
GSE169246_PacBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	post	NK cells	-0.352565	4.60e-40
GSE169246_PacBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	Mono/Macro	-0.987618	0.00e+00
GSE169246_PacBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	Plasma cells	-0.586013	1.37e-04
GSE169246_PacBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	cDCs	-0.710395	2.82e-15
GSE169246_PacTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	post	CD8+ T cells	0.411119	7.86e-34
GSE169246_PacTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	CD8+ T cells	-0.977164	0.00e+00
GSE169246_PacTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	Mono/Macro	-0.256102	2.86e-08
GSE169246_PacTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	CD4+ T cells	-0.483456	0.00e+00
GSE169246_PacTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Chemotherapy	paclitaxel	pre	Plasma cells	-0.514447	0.00e+00
GSE169246_PacAteBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	cDCs	0.306269	4.03e-04
GSE169246_PacAteBlood	patients	Peripheral blood mononuclear cells	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	pre	Mono/Macro	0.313137	3.55e-21
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	Plasma cells	1.55119	0.00e+00
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	CD4+ T cells	0.876207	0.00e+00
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	B cells	0.734802	0.00e+00
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	Mono/Macro	1.25536	9.24e-21
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	NK cells	0.854751	8.01e-09
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	post	CD8+ T cells	1.07943	0.00e+00
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	pre	B cells	0.484869	4.96e-33
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	pre	CD4+ T cells	0.810182	0.00e+00
GSE169246_PacAteTissue	patients	Tumor tissue	Breast cancer	Advanced triple-negative breast cancer (TNBC)	Immunotherapy	atezolizumab + paclitaxel	pre	Plasma cells	1.03185	0.00e+00
GSE197268_Axi-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	axi-cel (CAR-T)	post	Mono/Macro	-0.479039	0.00e+00
GSE197268_Axi-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	axi-cel (CAR-T)	post	NK cells	-0.384883	4.27e-10
GSE197268_Axi-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	axi-cel (CAR-T)	post	CD8+ T cells	-0.443788	0.00e+00
GSE197268_Axi-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	axi-cel (CAR-T)	post	CD4+ T cells	-0.278813	2.29e-05
GSE197268_Axi-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	axi-cel (CAR-T)	post	cDCs	-0.930967	7.70e-12
GSE197268_Axi-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	axi-cel (CAR-T)	pre	Mono/Macro	0.445721	0.00e+00
PMID34715028	patients	Tumor tissue	Kidney cancer	Clear cell renal cell carcinoma (ccRCC)	Immunotherapy	nivolumab	post	CD4+ T cells	-0.304331	1.13e-09
PMID34715028	patients	Tumor tissue	Kidney cancer	Clear cell renal cell carcinoma (ccRCC)	Immunotherapy	nivolumab	post	CD8+ T cells	-0.458728	0.00e+00
GSE164237	patients	Peripheral blood mononuclear cells	Melanoma	Advanced stages of melanoma	Immunotherapy	pembrolizumab	post	CD8+ T cells	0.256796	0.00e+00
GSE207422_Sin	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	sintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	Plasma cells	1.10899	3.03e-05
GSE207422_Sin	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	sintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	CD8+ T cells	1.44269	0.00e+00
GSE207422_Sin	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	sintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	Neutrophils	0.573662	1.56e-14
GSE207422_Sin	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	sintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	Mono/Macro	1.03825	1.66e-16
GSE207422_Sin	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	sintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	CD4+ T cells	1.07495	2.35e-39
GSE197268_Tisa-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	tisa-cel (CAR-T)	post	CD4+ T cells	0.387131	0.00e+00
GSE197268_Tisa-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	tisa-cel (CAR-T)	post	Mono/Macro	0.567101	0.00e+00
GSE197268_Tisa-cel	patients	Peripheral blood mononuclear cells	Acute lymphoblastic leukemia	Large B-cell acute lymphoblastic leukemia (B-ALL)	Immunotherapy	tisa-cel (CAR-T)	pre	Mono/Macro	0.801255	0.00e+00
GSE207422_Tor	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	toripalimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	Malignant cells	1.85441	0.00e+00
GSE207422_Tor	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	toripalimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	CD8+ T cells	0.452474	1.60e-02
GSE207422_Tor	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	toripalimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	Mono/Macro	0.939598	6.21e-14
GSE207422_Tor	patients	Tumor tissue	Lung cancer	EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)	Immunotherapy	toripalimab + carboplatin + (docetaxel or pemetrexed or emcitabine)	post	B cells	-0.905932	1.02e-07
GSE189460	patients	Bone marrow aspirate	Multiple myeloma	Multiple myeloma (MM)	Targeted therapy	bortezomib + melphalan + prednisolone	pre	CD8+ T cells	-0.386766	9.31e-16
GSE161801_PI	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	carfilzomib + dexamethasone	post	Mono/Macro	0.896304	0.00e+00
GSE161801_PI	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	carfilzomib + dexamethasone	post	Malignant cells	1.26308	0.00e+00
GSE161801_PI	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	carfilzomib + dexamethasone	post	CD8+ T cells	0.303103	1.11e-23
GSE161801_PI	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	carfilzomib + dexamethasone	pre	Mono/Macro	0.474082	1.16e-06
GSE161801_PI	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	carfilzomib + dexamethasone	pre	Malignant cells	0.963058	0.00e+00
GSE168668	LNCaP cell line	Cell line	Prostate cancer	Prostate cancer	Targeted therapy	enzalutamide	NA	Malignant cells	-0.263566	0.00e+00
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	post	Malignant cells	0.577931	0.00e+00
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	post	cDCs	0.39485	5.08e-09
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	post	Erythrocytes	0.720958	2.78e-03
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	pre	CD8+ T cells	0.484231	4.36e-11
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	pre	cDCs	1.27299	4.17e-05
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	pre	Malignant cells	0.844363	0.00e+00
GSE162117	patients	Peripheral blood mononuclear cells	Acute myeloid leukemia	Tefractory acute myeloid leukemia (AML)	Targeted therapy	ficlatuzumab	pre	CD4+ T cells	0.302656	3.43e-35
GSE161801_IMiD	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	pomalidomide + dexamethasone OR lenalidomide + dexamethasone	post	NK cells	0.589674	6.25e-07
GSE161801_IMiD	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	pomalidomide + dexamethasone OR lenalidomide + dexamethasone	pre	Mono/Macro	0.354092	2.95e-10
GSE161801_IMiD	patients	Bone marrow aspirate	Multiple myeloma	Refractory multiple myeloma (MM)	Targeted therapy	pomalidomide + dexamethasone OR lenalidomide + dexamethasone	pre	Malignant cells	0.331766	2.80e-45
GSE175716	PDX	Tumor tissue	Liver cancer	Advanced hepatocellular carcinoma	Targeted therapy	sorafenib	NA	Malignant cells	-0.931189	0.00e+00

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Expression of IFI6 in the resistant group across all datasets and cell types

Red dots represent significantly high expression in the resistant group, while blue dots represent significantly low expression in the resistant group. White dots represent that there is no significant difference in the expression of this gene between the resistant and sensitive groups. Blank represents that this cell type is not present in this dataset. (If the image exists, the user can click on it to enlarge it in a new window.)

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Significant ligand-receptor pairs related to IFI6

This table shows the significant ligand-receptor pairs related to this gene across all datasets, timepoints and conditions. (Complete files can be downloaded from the download section.)

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Known drug resistance mechanisms of this gene

This table shows the known drug resistance mechanisms of this gene. Clicking on this gene will link to another database that displays more drug resistance-related information.

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MicroRNAs (miRNA) regulating IFI6

This table shows the miRNAs with a score of more than 80 regulating this gene. (Complete files can be downloaded from the download section.)

Gene symbol	miRNA	Score	GeneBank accession
IFI6	hsa-miR-5704	91.2076	NM_002038
IFI6	hsa-miR-6776-5p	90.3351	NM_022872
IFI6	hsa-miR-373-5p	90.0451	NM_022872
IFI6	hsa-miR-616-5p	90.0451	NM_022872
IFI6	hsa-miR-371b-5p	90.0451	NM_022872
IFI6	hsa-miR-3613-3p	84.5864	NM_022872
IFI6	hsa-miR-5706	82.5257	NM_002038
IFI6	hsa-miR-4782-5p	82.5257	NM_002038
IFI6	hsa-miR-6763-5p	82.1993	NM_022872
IFI6	hsa-miR-3150a-3p	82.1993	NM_022872
IFI6	hsa-miR-6077	81.4012	NM_022872
IFI6	hsa-miR-6780a-5p	80.445	NM_022872

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Motifs and transcription factors (TFs) regulating IFI6

This table shows the Motifs and transcription factors (TFs) regulating this gene. (Complete files can be downloaded from the download section.)

Gene symbol	motif	TF_highConf
IFI6	metacluster_27.20	ZNF708; ZNF787; ZNF787; ZNF85 (directAnnotation).
IFI6	metacluster_168.11	ZNF771; ZNF771 (directAnnotation).
IFI6	kznf__ZNF737_Imbeault2017_OM_MEME	ZNF737 (directAnnotation).
IFI6	tfdimers__MD00123	E2F1; SOX17 (directAnnotation).
IFI6	transfac_pro__M06608	ZNF486 (directAnnotation).
IFI6	tfdimers__MD00138	IRF1; IRF2; IRF3; IRF4; IRF5; IRF7; IRF8; IRF9; MYB (directAnnotation).
IFI6	transfac_pro__M05550	SNAPC4 (inferredBy_Orthology).
IFI6	transfac_pro__M05894	ZNF565 (directAnnotation).
IFI6	taipale_cyt_meth__ELF3_NTGTGCGGATGCN_FL_repr	ELF3 (directAnnotation).
IFI6	transfac_pro__M01108	HOXA7 (directAnnotation).
IFI6	homer__HNRAATCAAT_Cux2	CUX2 (inferredBy_Orthology).
IFI6	transfac_pro__M07612	SFPQ (directAnnotation).
IFI6	transfac_pro__M05997	ZFP64 (directAnnotation).
IFI6	transfac_pro__M06529	ZNF596 (directAnnotation).
IFI6	taipale_tf_pairs__CUX1_SOX15_ATCRATNNNNNNNNSYATTGTT_CAP_repr	CUX1; SOX15 (directAnnotation).
IFI6	transfac_pro__M05908	ZNF319 (inferredBy_Orthology).
IFI6	metacluster_65.19	HSF1 (directAnnotation).
IFI6	transfac_pro__M04960	POU5F1 (directAnnotation).
IFI6	homer__TATTGAYY_Hnf6b	ONECUT2 (directAnnotation).
IFI6	transfac_pro__M06745	ZNF780B (directAnnotation).
IFI6	transfac_pro__M05901	ZNF561 (directAnnotation).
IFI6	taipale_tf_pairs__FOXJ3_ELF1_NNARAAAACCGAAWMN_CAP	ELF1; FOXJ3 (directAnnotation).
IFI6	taipale_tf_pairs__FOXO1_ELF1_NNGAAAACCGAANM_CAP	ELF1; FOXO1 (directAnnotation).
IFI6	kznf__ZNF334_Imbeault2017_OM_MEME	ZNF334 (directAnnotation).
IFI6	metacluster_165.9	CUX1; CUX2 (directAnnotation).
IFI6	taipale__IRF7_DBD_RAANCGAAAWTCGNTTY_repr	IRF7 (directAnnotation).
IFI6	metacluster_80.16	ZIC1 (directAnnotation). ZIC2 (inferredBy_Orthology).
IFI6	swissregulon__mm__Zbtb12	ZBTB12 (inferredBy_Orthology).
IFI6	taipale_tf_pairs__FOXJ2_ELF1_RMAGAAAACCGAANN_CAP_repr	ELF1; FOXJ2 (directAnnotation).
IFI6	tfdimers__MD00380	ARID3A; ING4 (directAnnotation).
IFI6	tfdimers__MD00190	ARID3A; WT1 (directAnnotation).
IFI6	kznf__ZNF302_Imbeault2017_OM_RCADE	ZNF302 (directAnnotation).
IFI6	metacluster_85.6	ZNF74 (directAnnotation).
IFI6	transfac_pro__M06665	ZNF599 (directAnnotation).
IFI6	transfac_pro__M04849	RELA (directAnnotation).
IFI6	transfac_pro__M06787	ZNF780B (directAnnotation).
IFI6	transfac_pro__M05615	ZFP2 (inferredBy_Orthology).
IFI6	homer__GGAAATTCCC_NFkB-p65-Rel	RELA (inferredBy_Orthology).
IFI6	transfac_pro__M06646	ZNF607 (directAnnotation).
IFI6	transfac_pro__M04912	FOXA1 (directAnnotation).
IFI6	transfac_pro__M05782	ZNF324B (directAnnotation).
IFI6	transfac_pro__M06918	ZNF652 (directAnnotation).
IFI6	transfac_pro__M05560	AEBP2 (directAnnotation).
IFI6	flyfactorsurvey__pho_SOLEXA_F1-3	YY1 (inferredBy_Orthology).
IFI6	kznf__ZSCAN29_TF_Evolution_PBM	ZSCAN29 (directAnnotation).
IFI6	transfac_pro__M04858	THAP1 (directAnnotation).
IFI6	transfac_pro__M05605	GATA6 (inferredBy_Orthology).
IFI6	transfac_pro__M02832	ZNF410 (inferredBy_Orthology).
IFI6	cisbp__M05847	ZKSCAN1 (directAnnotation).
IFI6	kznf__ZNF135_Imbeault2017_OM_RCADE	ZNF135 (directAnnotation).

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Acts as a transcription factor

This table shows that this differential gene acts as a transcription factor.

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Acts as a drug target

This table shows that this differential gene acts as a drug target.

1	"Sun X, Zhang Y, Li H, Zhou Y, Shi S, Chen Z, He X, Zhang H, Li F, Yin J, Mou M, Wang Y, Qiu Y, Zhu F. DRESIS: the first comprehensive landscape of drug resistance information. Nucleic Acids Res. 2023 Jan 6;51(D1):D1263-D1275. doi: 10.1093/nar/gkac812. PMID: 36243960; PMCID: PMC9825618."
2	"Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037. PMID: 29126136; PMCID: PMC5753335."