MICB Gene

HGNC Family	Immunoglobulin superfamily domain containing
Name	MHC class I polypeptide-related sequence B
Description	This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMICB is a stress‐inducible ligand belonging to the MHC class I–related family that participates in immune surveillance by engaging the activating receptor NKG2D on natural killer cells and certain T‐cell subsets. Under conditions of cellular stress such as viral infection and malignant transformation, MICB (along with its closely related partner MICA) is upregulated on the cell surface to signal danger and trigger cytotoxic responses; however, persistent engagement or shedding of MICB can lead to downregulation of NKG2D on effector cells, thereby undermining antitumor immunity. In some viral infections, for example, human cytomegalovirus employs specific microRNAs to target and reduce MICB expression, contributing to viral immune evasion. Expression studies in epithelial tumours, leukemia, and hepatocellular carcinoma have further underscored a dual role of MICB in stimulating immune responses while its soluble forms may impair them."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have implicated MICB in disease progression in immune‐mediated conditions and infections, with variants in the MICB gene linked to differential outcomes in AIDS progression and susceptibility to inflammatory shock. In the tumour microenvironment, proteolytic shedding of MICB by metalloproteases such as ADAM10 and ADAM17 leads to increased levels of soluble MICB, which in turn may blunt NKG2D‐mediated cytotoxicity, favoring tumour immune escape. Such shedding mechanisms and the soluble versus membrane-bound states of MICB have been shown to differentially impact natural killer cell function in various experimental models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTherapeutically, modulation of MICB expression and/or its shedding has clinical relevance. Treatment strategies that upregulate cell surface MICB (or prevent its shedding) can enhance NKG2D-dependent clearance of tumour cells, as evidenced by studies where pharmacologic modulation increased leukemic cell susceptibility to natural killer cell killing. Engineered models contrasting membrane-restricted MICB with its soluble counterpart have highlighted that sustained cell surface expression supports long-term antitumour immunity, while elevated soluble MICB levels are associated with poor clinical outcomes, suggesting that broader transcription of MICB may be more prevalent than previously appreciated."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Veronika Groh, Jennifer Wu, Cassian Yee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01112"}], "href": "https://doi.org/10.1038/nature01112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12384702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12384702"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Noam Stern-Ginossar, Naama Elefant, Albert Zimmermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Host immune system gene targeting by a viral miRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1140956"}], "href": "https://doi.org/10.1126/science.1140956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17641203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17641203"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Helmut Rainer Salih, Holger Antropius, Friederike Gieseke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-01-0019"}], "href": "https://doi.org/10.1182/blood-2003-01-0019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12714493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12714493"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ekaterina S Doubrovina, Mikhail M Doubrovin, Elena Vider, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.171.12.6891"}], "href": "https://doi.org/10.4049/jimmunol.171.12.6891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14662896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14662896"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masahisa Jinushi, Tetsuo Takehara, Tatsuya Kanto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of MHC class I-related chain A and B expression on IFN-alpha-stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.3.1249"}], "href": "https://doi.org/10.4049/jimmunol.170.3.1249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12538683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12538683"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Masahisa Jinushi, Tetsuo Takehara, Tomohide Tatsumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.10966"}], "href": "https://doi.org/10.1002/ijc.10966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12569559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12569559"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sophie Limou, Sigrid Le Clerc, Cédric Coulonges, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Infect Dis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/596067"}], "href": "https://doi.org/10.1086/596067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19115949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19115949"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chiea Chuen Khor, Tran Nguyen Bich Chau, Junxiong Pang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.960"}], "href": "https://doi.org/10.1038/ng.960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22001756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22001756"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Guranda Chitadze, Marcus Lettau, Jaydeep Bhat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shedding of endogenous MHC class I-related chain molecules A and B from different human tumor entities: heterogeneous involvement of the \"a disintegrin and metalloproteases\" 10 and 17."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.28174"}], "href": "https://doi.org/10.1002/ijc.28174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23526433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23526433"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Helmut Rainer Salih, Dennis Goehlsdorf, Alexander Steinle "}, {"type": "b", "children": [{"type": "t", "text": "Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humimm.2006.02.008"}], "href": "https://doi.org/10.1016/j.humimm.2006.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16698441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16698441"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Pinchas Tsukerman, Noam Stern-Ginossar, Chamutal Gur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-2671"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-2671"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22915757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22915757"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Gang Liu, Shengjun Lu, Xuanjun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Perturbation of NK cell peripheral homeostasis accelerates prostate carcinoma metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI69369"}], "href": "https://doi.org/10.1172/JCI69369"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24018560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24018560"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "H Nückel, M Switala, L Sellmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2010.74"}], "href": "https://doi.org/10.1038/leu.2010.74"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20428196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20428196"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hormas Ghadially, Lee Brown, Chris Lloyd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2017.79"}], "href": "https://doi.org/10.1038/bjc.2017.79"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28334733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28334733"}]}]}]}
Synonyms	PERB11.2
Proteins	MICB_HUMAN
NCBI Gene ID	4277
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MICB has 6,940 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for MICB from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MICB Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MICB gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MICB gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of MICB gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MICB gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of MICB gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MICB gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MICB gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MICB gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MICB gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MICB gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of MICB gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MICB protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MICB gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MICB gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of MICB gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MICB protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MICB gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MICB protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MICB protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MICB protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with MICB protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing MICB protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MICB gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MICB gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MICB gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MICB gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MICB gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MICB protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MICB gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MICB gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MICB gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MICB gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with MICB gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with MICB gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MICB gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MICB gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MICB gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MICB gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing MICB from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with MICB gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.