B2M beta-2-microglobulin [Homo sapiens (human)] - Gene

Summary

Official Symbol: B2Mprovided by HGNC
Official Full Name: beta-2-microglobulinprovided by HGNC
Primary source: HGNC:HGNC:914
See related: Ensembl:ENSG00000166710 MIM:109700
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IMD43
Summary: This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. The encoded antimicrobial protein displays antibacterial activity in amniotic fluid. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.[provided by RefSeq, Aug 2014]
Expression: Ubiquitous expression in spleen (RPKM 1527.0), lymph node (RPKM 1335.3) and 24 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 15q21.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	15	NC_000015.10 (44711487..44718159)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (45003685..45010357)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Study observed differences in B2M mutation status in mismatch repair-deficient CRC by tumor subtypes, site, stage, grade, immune infiltrate and for overall survival that warrant further investigation in larger studies before B2M mutation status can be considered to have clinical utility.
Title: Somatic mutations of the coding microsatellites within the beta-2-microglobulin gene in mismatch repair-deficient colorectal cancers and adenomas.
Data show that plasma beta2-microglobulin (beta2m) levels are specifically increased in Alzheimer's disease (AD), indicating that beta2m could play a role in AD.
Title: Comparison of β2-microglobulin serum level between Alzheimer's patients, cognitive healthy and mild cognitive impaired individuals.
Binding stability to beta2-microglobulin may confer to HLA-C the ability to preferentially act either as a conventional immune-competent molecule or as an accessory molecule involved in HIV-1 infectivity via viral envelope glycoprotein binding.
Title: HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity.
Molecular dynamic simulations reveal that D59P mutation in the DE loop region of B2M disrupts the native sandwich folded structure and highlight a decrease in the average number of hydrogen bonds in the loop regions on D59P mutation that enhances conformational flexibility, which lead to higher aggregation propensity.
Title: Assessing the effect of D59P mutation in the DE loop region in amyloid aggregation propensity of β2-microglobulin: A molecular dynamics simulation study.
Study characterized the salt-induced oligomers of the acid-unfolded state of beta2m using an array of biophysical tools including steady-state and time-resolved fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy imaging. Results revealed the distinct pathways by which beta2m assembles into oligomers and fibrils.
Title: Characterization of Salt-Induced Oligomerization of Human β2-Microglobulin at Low pH.
We focused on the genetic and functional analysis of beta2-microglobulin (B2M), a component of the HLA class-I complex. We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance
Title: Genomic Profiling of Patient-Derived Xenografts for Lung Cancer Identifies <i>B2M</i> Inactivation Impairing Immunorecognition.
Pretransplant beta2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.(
Title: Pretransplant β2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.
we found that beta2M but no other serum markers had independent prognostic significance in the UK CLL4 trial
Title: Evaluation of serum markers in the LRF CLL4 trial: β2-microglobulin but not serum free light chains, is an independent marker of overall survival.
Both cystatin C and beta 2 macroglobulin are elevated in type 2 diabetics with diabetic nephropathy.
Title: Clinical Implication of Cystatin C and β2-Microglobulin in Early Detection of Diabetic Nephropathy.
Serum B2M level was positively associated with Gensini score system, SYNTAX score system and the number of diseased coronary vessels.
Title: High levels of serum β2-microglobulin predict severity of coronary artery disease.

Submit: New GeneRIF Correction See all GeneRIFs (260)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Familial visceral amyloidosis, Ostertag type MedGen: C0268389 OMIM: 105200 GeneReviews: Not available	Compare labs
Hypoproteinemia, hypercatabolic MedGen: C1855796 OMIM: 241600 GeneReviews: Not available	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Both HIV-1 Nef and Vpu downregulate the cell surface expression of beta-2-microglobulin (B2M)	PubMed
Tat	tat	HIV-1 Tat represses transcription of the beta 2-microglobulin (B2M) promoter, thereby downregulating B2M expression, suggesting a mechanism by which HIV-1 could prevent cell surface expression of the MHC class I complex and avoid immune detection	PubMed
Vpu	vpu	Both HIV-1 Nef and Vpu downregulate the cell surface expression of beta-2-microglobulin (B2M)	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

Go to the top of the page Help

Adaptive Immune System, organism-specific biosystem (from REACTOME)
Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
Amyloid fiber formation, organism-specific biosystem (from REACTOME)
Amyloid fiber formation, organism-specific biosystemAmyloid is a term used to describe deposits of fibrillar proteins, typically extracellular. The abnormal accumulation of amyloid, amyloidosis, is a term associated with tissue damage caused by amyloi...
Antigen Presentation: Folding, assembly and peptide loading of class I MHC, organism-specific biosystem (from REACTOME)
Antigen Presentation: Folding, assembly and peptide loading of class I MHC, organism-specific biosystemUnlike other glycoproteins, correct folding of MHC class I molecules is not sufficient to trigger their exit from the ER, they exit only after peptide loading. Described here is the process of antige...
Antigen processing and presentation, organism-specific biosystem (from KEGG)
Antigen processing and presentation, organism-specific biosystem
Antigen processing and presentation
Antigen processing and presentation, conserved biosystem (from KEGG)
Antigen processing and presentation, conserved biosystem
Antigen processing and presentation
Antigen processing-Cross presentation, organism-specific biosystem (from REACTOME)
Antigen processing-Cross presentation, organism-specific biosystemMHC class I molecules generally present peptide antigens derived from proteins synthesized by the cell itself to CD8+ T cells. However, in some circumstances, antigens from extracellular environment ...
Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
DAP12 interactions, organism-specific biosystem (from REACTOME)
DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
DAP12 signaling, organism-specific biosystem (from REACTOME)
DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
Downstream signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
Downstream signaling in naive CD8+ T cells, organism-specific biosystem
Downstream signaling in naive CD8+ T cells
ER-Phagosome pathway, organism-specific biosystem (from REACTOME)
ER-Phagosome pathway, organism-specific biosystemThe other TAP-dependent cross-presentation mechanism in phagocytes is the endoplasmic reticulum (ER)-phagosome model. Desjardins proposed that ER is recruited to the cell surface, where it fuses wit...
Endosomal/Vacuolar pathway, organism-specific biosystem (from REACTOME)
Endosomal/Vacuolar pathway, organism-specific biosystemSome antigens are cross-presented through a vacuolar mechanism that involves generation of antigenic peptides and their loading on to MHC-I molecules within the endosomal compartment in a proteasome ...
HIV Infection, organism-specific biosystem (from REACTOME)
HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
Host Interactions of HIV factors, organism-specific biosystem (from REACTOME)
Host Interactions of HIV factors, organism-specific biosystemLike all viruses, HIV-1 must co-opt the host cell macromolecular transport and processing machinery. HIV-1 Vpr and Rev proteins play key roles in this co-optation. Efficient HIV-1 replication likewis...
IL12-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
IL12-mediated signaling events, organism-specific biosystem
IL12-mediated signaling events
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
Infectious disease, organism-specific biosystem (from REACTOME)
Infectious disease, organism-specific biosystem
Infectious disease
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Interferon Signaling, organism-specific biosystem (from REACTOME)
Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
Interferon gamma signaling, organism-specific biosystem (from REACTOME)
Interferon gamma signaling, organism-specific biosystemInterferon-gamma (IFN-gamma) belongs to the type II interferon family and is secreted by activated immune cells-primarily T and NK cells, but also B-cells and APC. INFG exerts its effect on cells by ...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Nef mediated downregulation of MHC class I complex cell surface expression, organism-specific biosystem (from REACTOME)
Nef mediated downregulation of MHC class I complex cell surface expression, organism-specific biosystemDown-regulation of MHC class I involves Nef-mediated connection in the endosomes between MHC-I's cytoplasmic tail and the phosphofurin acidic cluster sorting protein-1 (PACS-1)-dependent protein-sort...
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters, organism-specific biosystem (from REACTOME)
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters, organism-specific biosystemThe maximal virulence of HIV-1 requires Nef, a virally encoded peripheral membrane protein. Nef binds to the adaptor protein (AP) complexes of coated vesicles, inducing an expansion of the endosomal ...
Neutrophil degranulation, organism-specific biosystem (from REACTOME)
Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
TCR signaling in naive CD8+ T cells, organism-specific biosystem
TCR signaling in naive CD8+ T cells
The role of Nef in HIV-1 replication and disease pathogenesis, organism-specific biosystem (from REACTOME)
The role of Nef in HIV-1 replication and disease pathogenesis, organism-specific biosystemThe HIV-1 Nef protein is a 27-kDa myristoylated protein that is abundantly produced during the early phase of viral replication cycle. It is highly conserved in all primate lentiviruses, suggesting t...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

GDB:454836 (e-PCR)
- UniSTS:157450

RH76 (e-PCR)
- UniSTS:65809

STS-S82300 (e-PCR)
- UniSTS:54814

D15S799 (e-PCR)
- UniSTS:10275

PMC151806P1 (e-PCR)
- UniSTS:271179

PMC316580P7 (e-PCR)
- UniSTS:273014

SGC31499 (e-PCR)
- UniSTS:27771

PMC126239P1 (e-PCR)
- UniSTS:270533

G62079 (e-PCR)
- UniSTS:139221

Homology

Homologs of the B2M gene: The B2M gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 187 organisms have orthologs with human gene B2M
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
T cell differentiation in thymus	IEA Inferred from Electronic Annotation more info
antigen processing and presentation of endogenous peptide antigen via MHC class I	IGI Inferred from Genetic Interaction more info	PubMed
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS Traceable Author Statement more info
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent	TAS Traceable Author Statement more info
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent	IEA Inferred from Electronic Annotation more info
antigen processing and presentation of peptide antigen via MHC class I	TAS Traceable Author Statement more info
cellular protein metabolic process	TAS Traceable Author Statement more info
cellular response to iron ion	IGI Inferred from Genetic Interaction more info	PubMed
cellular response to iron(III) ion	IEA Inferred from Electronic Annotation more info
innate immune response	TAS Traceable Author Statement more info
interferon-gamma-mediated signaling pathway	TAS Traceable Author Statement more info
iron ion homeostasis	IC Inferred by Curator more info	PubMed
iron ion transport	IEA Inferred from Electronic Annotation more info
negative regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
negative regulation of receptor binding	IDA Inferred from Direct Assay more info	PubMed
neutrophil degranulation	TAS Traceable Author Statement more info
positive regulation of T cell cytokine production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of T cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
positive regulation of ferrous iron binding	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of protein binding	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of receptor binding	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of receptor-mediated endocytosis	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of transferrin receptor binding	IGI Inferred from Genetic Interaction more info	PubMed
protein refolding	IEA Inferred from Electronic Annotation more info
regulation of defense response to virus by virus	TAS Traceable Author Statement more info
regulation of erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
regulation of immune response	TAS Traceable Author Statement more info
regulation of iron ion transport	IGI Inferred from Genetic Interaction more info	PubMed
response to cadmium ion	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
response to molecule of bacterial origin	IEA Inferred from Electronic Annotation more info
retina homeostasis	HEP more info	PubMed

Component	Evidence Code	Pubs
ER to Golgi transport vesicle membrane	TAS Traceable Author Statement more info
Golgi apparatus	IDA Inferred from Direct Assay more info
Golgi membrane	TAS Traceable Author Statement more info
HFE-transferrin receptor complex	IDA Inferred from Direct Assay more info	PubMed
MHC class I protein complex	IEA Inferred from Electronic Annotation more info
cytosol	IDA Inferred from Direct Assay more info
early endosome lumen	TAS Traceable Author Statement more info
early endosome membrane	TAS Traceable Author Statement more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
external side of plasma membrane	IEA Inferred from Electronic Annotation more info
extracellular exosome	HDA more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	HDA more info	PubMed
focal adhesion	HDA more info	PubMed
membrane	HDA more info	PubMed
phagocytic vesicle membrane	TAS Traceable Author Statement more info
plasma membrane	IDA Inferred from Direct Assay more info
plasma membrane	TAS Traceable Author Statement more info
recycling endosome membrane	TAS Traceable Author Statement more info
specific granule lumen	TAS Traceable Author Statement more info
tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: beta-2-microglobulin

Names: beta chain of MHC class I molecules; beta-2-microglobin

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.