B2M

Summary

B2M (beta-2-microglobulin, HGNC:914) is a protein-coding gene on chromosome 15q21.1, encoding Beta-2-microglobulin (P61769). Component of the class I major histocompatibility complex (MHC). In precision oncology, B2M S14FS is associated with resistance to Pembrolizumab in Skin Melanoma (CIViC Level C).

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.

Source: NCBI Gene 567 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypoproteinemia, hypercatabolic (Strong, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 104 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 7 cancer types
• MANE Select transcript: NM_004048

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:914
Approved symbol	B2M
Name	beta-2-microglobulin
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166710
Ensembl biotype	protein_coding
OMIM	109700
Entrez	567

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000349264, ENST00000557901, ENST00000559720, ENST00000559907, ENST00000559916, ENST00000560556, ENST00000560681, ENST00000561139, ENST00000561424, ENST00000623550, ENST00000648006, ENST00000695792, ENST00000906076, ENST00000906077, ENST00000916438

RefSeq mRNA: 1 — MANE Select: NM_004048 NM_004048

CCDS: CCDS10113

Canonical transcript exons

ENST00000617605 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3314.2823 / max 69373.7594, expressed in 1828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146382	3309.7016	1828
146385	3.4937	1066
146383	1.0870	524

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.99	gold quality
monocyte	CL:0000576	99.99	gold quality
leukocyte	CL:0000738	99.99	gold quality
vermiform appendix	UBERON:0001154	99.99	gold quality
gall bladder	UBERON:0002110	99.99	gold quality
lymph node	UBERON:0000029	99.98	gold quality
rectum	UBERON:0001052	99.97	gold quality
spleen	UBERON:0002106	99.97	gold quality
right lung	UBERON:0002167	99.97	gold quality
upper lobe of left lung	UBERON:0008952	99.97	gold quality
stromal cell of endometrium	CL:0002255	99.96	gold quality
blood	UBERON:0000178	99.96	gold quality
calcaneal tendon	UBERON:0003701	99.96	gold quality
islet of Langerhans	UBERON:0000006	99.95	gold quality
adipose tissue	UBERON:0001013	99.95	gold quality
smooth muscle tissue	UBERON:0001135	99.95	gold quality
placenta	UBERON:0001987	99.95	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.95	gold quality
mucosa of transverse colon	UBERON:0004991	99.95	gold quality
left lobe of thyroid gland	UBERON:0001120	99.94	gold quality
right adrenal gland	UBERON:0001233	99.94	gold quality
endometrium	UBERON:0001295	99.94	gold quality
thyroid gland	UBERON:0002046	99.94	gold quality
duodenum	UBERON:0002114	99.94	gold quality
bone marrow	UBERON:0002371	99.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.94	gold quality
omental fat pad	UBERON:0010414	99.94	gold quality
metanephros cortex	UBERON:0010533	99.94	gold quality
right lobe of thyroid gland	UBERON:0001119	99.93	gold quality

Single-cell (SCXA)

Detected in 74 experiment(s), a significant marker in 45.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	55889.65
E-GEOD-149689	yes	30093.16
E-MTAB-8142	yes	28703.09
E-HCAD-11	yes	25987.74
E-MTAB-6701	yes	25432.67
E-HCAD-1	yes	22948.43
E-MTAB-8410	yes	22850.40
E-GEOD-134144	yes	22473.89
E-MTAB-6678	yes	20925.40
E-HCAD-4	yes	19751.59
E-CURD-46	yes	18300.12
E-GEOD-130148	yes	17454.17
E-CURD-79	yes	16968.50
E-MTAB-7407	yes	16901.82
E-MTAB-10885	yes	15310.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB, MYC, NFKB1, NFKB2, RELA, SPI1, TP53, USF1, USF2

miRNA regulators (miRDB)

47 targeting B2M, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954

Literature-anchored findings (GeneRIF, showing 40)

• structure in amyloid fibril formation (PMID:11676539)
• cleaved form partially attains a conformation that has amyloidogenic features (PMID:11801591)
• solution structure determined by (1)H NMR spectroscopy and restrained modeling calculations (PMID:11847272)
• Signal transduction of beta2m-induced expression of VCAM-1 and COX-2 in synovial fibroblasts. (PMID:11849381)
• Strong associations were found between B2M serum levels and chromosome 14q32 abnormalities, but not del(13), in multiple myeloma. (PMID:11877296)
• basis in developing CD8+ T cell antagonists (PMID:11914379)
• Conformation of beta 2-microglobulin amyloid fibrils analyzed by reduction of the disulfide bond (PMID:11943769)
• equilibrium denaturation measured by (1)H-(15)N NMR to determine conformational properties of an amyloidogenic intermediate of human beta(2)-microglobulin (beta(2)m) formed at low pH (PMID:11967566)
• Mapping the core of the beta(2)-microglobulin amyloid fibril by H/D exchange (PMID:11967567)
• Assembly of the FcRn alpha-chain with beta(2)microglobulin is important for both transport of FcRn from the ER to the cell surface and efficient pH-dependent IgG binding. (PMID:12006623)
• Functional reconstitution of human FcRn in Madin-Darby canine kidney cells required co-expression (PMID:12023961)
• Increased expression of beta 2-microglobulin is associated with multiple drug resistance in tumor cells (PMID:12085191)
• Crystal structure reveals clues to its amyloidogenic properties (PMID:12119416)
• Results suggest that the reduced mobility of the denatured state is an important factor for the amylodogenic potential of beta2-microglobulin. (PMID:12192077)
• A dominant negative mutant of this protein blocks the extracellular folding of MHC I heavy chain (PMID:12454016)
• results suggest that the apparent iron-deficient phenotype elicited by haemochromatosis protein (HFE) is not linked to beta(2)microglobulin insufficiency (PMID:12464008)
• Beta2-microglobulin aberrations in diffuse large B-cell lymphoma of the testis and the central nervous system. (PMID:12471623)
• USF1 & USF2 bind to the B2M E box & regulate its transactivation. NF-kappa B subunits p50 & p65 bind to the kappa B box & p65 transactivates beta(2)m. IRFs1, 2,4,& 8 but not PU.1, bind to the Ets/ISRE. IRF1 & IRF3 are strong transactivators of beta(2)m. (PMID:12480693)
• taken up by synovial fibroblasts and macrophages of patients with osteoarthritis (PMID:12480959)
• Data suggest that residues 59-71 may be important in the self-association of partially folded beta(2)microglobulin into amyloid fibrils. (PMID:12488093)
• Block of b2m expression results in complete loss of HLA class I antigen expression on melanoma cells and disease progression (PMID:12516095)
• high concentrations retards the generation of monocyte-derived dendritic cells, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-kappaB, and activation of STAT3 (PMID:12531797)
• a possible marker of renal function in patients with type 2 diabetes mellitus (PMID:12738401)
• Our analysis suggests that the favored monomer building block for fibril elongation is the conformation of the isolated beta(2)-microglobulin, without the beta-bulge on strand D and without strands A and G participating in the fibril beta-sheet structure (PMID:12818210)
• atomic force microscopy study of beta-2 microglobulin (PMID:12850147)
• beta 2-microglobulin N and C-terminal strands have roles in amyloid formation at neutral pH (PMID:12860117)
• analysis of beta 2-microglobulin amyloid formation with destabilized proteins (PMID:12860118)
• Some glycosaminoglycans and proteoglycans could enhance deposition of beta2m amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of beta2m in the fibrils (PMID:12911560)
• mutations in which proline was introduced to each of the beta-strands of B2M affected the amyloidogenic potential of B2M to various degrees, and demonstrated that stability of the amyloid fibrils is a key factor determining the amyloidogenic potential (PMID:12958308)
• examined the unfolding processes of B2M and two related variants, a DeltaN6 and a Lys57-Asp58 cleavage, by high-temperature molecular dynamics simulations. Conformational changes of variants may relate to polymerization tendencies related to amyloidosis. (PMID:12968074)
• Causes dialysis-related amyloidosis, by virtue of its retention when renal function fails, its deposition in tissues, its aggregation into fibrils, and its ability to become glycosylated. Review. (PMID:14681859)
• structure activity relationship; His31–>Tyr human beta2m mutant, a non-natural form of beta2m that is more stable than the wild-type protein, displaying a ten-fold acceleration of the slow phase of folding (PMID:14698299)
• the internal structures are similar for beta2-microglobulin and amyloid fibril protein (PMID:14699107)
• B2M serum levels can be used as a marker for early diagnosis of cytomegalovirus infection after kidney transplantation. (PMID:15194307)
• Results show that a seven-residue segment of human beta2-microglobulin (beta2M), not found in mouse beta2M, is sufficient to convert beta2M to the amyloid state, and that specific residue interactions are crucial to the conversion. (PMID:15249659)
• beta(2)-microglobulin shows a similar heat capacity change upon amyloid formation to that of the folding to the native globular state, whereas the enthalpy change of the reaction is lower (PMID:15494406)
• effects of guanidine hydrochloride on the amyloid fibrils of beta2-m reveal a cooperative unfolding transition similar to that of the native state. (PMID:15498554)
• an unfolded beta(2)m at C-terminal is found in hemodialysis-related amyloidosis (PMID:15610257)
• There is an optimal concentration of salts required for efficient fibril growth of beta 2-microglobulin, suggesting that counterion interaction is crucial in amyloid formation. (PMID:15667222)
• Unfolded delta lysine-58-cleaved beta2m, a slightly modified beta 2-microglobulin variant generated by limited proteolysis, may behave as a monomeric amyloidogenic intermediate under physiologic conditions. (PMID:15766269)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zmp:0000001138	ENSDARG00000071168
mus_musculus	B2m	ENSMUSG00000060802
rattus_norvegicus	B2m	ENSRNOG00000017123

Paralogs (13): HLA-DQB1 (ENSG00000179344), HLA-DRB1 (ENSG00000196126), HLA-DQA1 (ENSG00000196735), HLA-DRB5 (ENSG00000198502), HLA-DOA (ENSG00000204252), HLA-DMA (ENSG00000204257), HLA-DRA (ENSG00000204287), HLA-DPB1 (ENSG00000223865), HLA-DPA1 (ENSG00000231389), HLA-DQB2 (ENSG00000232629), HLA-DQA2 (ENSG00000237541), HLA-DOB (ENSG00000241106), HLA-DMB (ENSG00000242574)

Protein

Protein identifiers

Beta-2-microglobulin — P61769 (reviewed: P61769)

All UniProt accessions (4): P61769, H0YLF3, J3KNU0, Q16446

UniProt curated annotations — full annotation on UniProt →

Function. Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation.

Subunit / interactions. Heterodimer of an alpha chain and a beta chain. Beta-2-microglobulin is the beta-chain of major histocompatibility complex class I molecules. Polymers of beta 2-microglobulin can be found in tissues from patients on long-term hemodialysis. B2M alone (not in complex with HLA-I) interacts with M.tuberculosis EsxA (ESAT-6) and an EsxA-EsxB (CFP-10) complex; the tripartite complex can be detected in the host endoplasmic reticulum. The B2M-EsxA complex can be detected in patients with pleural tuberculosis and is stable from pH 4.0 to 8.0 and in the presence of 2M NaCl. Forms a heterotrimer with HLA-E and a self- or a foreign peptide. Forms a heterotrimer with HLA-G and a self-peptide. Forms a heterotrimer with HLA-F and a self-peptide. Forms a heterotrimer with MR1 and a metabolite antigen.

Subcellular location. Secreted. Cell surface.

Post-translational modifications. Glycation of Ile-21 is observed in long-term hemodialysis patients.

Disease relevance. Immunodeficiency 43 (IMD43) [MIM:241600] A disorder characterized by marked reduction in serum concentrations of immunoglobulins and albumin, and hypoproteinemia due to hypercatabolism. Patients may suffer from recurrent respiratory tract infections and severe skin disease. The disease is caused by variants affecting the gene represented in this entry. Amyloidosis, hereditary systemic 6 (AMYLD6) [MIM:620659] A form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD6 is mainly characterized by gastrointestinal and cardiac symptoms. Neurologic involvement, sicca syndrome, and carpal tunnel syndrome may also be present. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Apart from the presence of causative mutations, beta-2-microglobulin may adopt the fibrillar configuration of amyloid, resulting in amyloidosis, when its serum levels are persistently high, as seen in patients on long-term hemodialysis. In contrast to patients with dialysis-related amyloidosis, patients with hereditary amyloidosis have normal circulating concentrations of beta2-microglobulin.

Similarity. Belongs to the beta-2-microglobulin family.

RefSeq proteins (1): NP_004039* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003006	Ig/MHC_CS	Conserved_site
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015707	B2Microglobulin	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050160	MHC/Immunoglobulin	Family

Pfam: PF07654

UniProt features (36 total): strand 12, glycosylation site 7, mutagenesis site 3, sequence conflict 3, chain 2, sequence variant 2, turn 2, signal peptide 1, disulfide bond 1, helix 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

1226 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4E0K	X-RAY DIFFRACTION	0.97
1K5N	X-RAY DIFFRACTION	1.09
3MRE	X-RAY DIFFRACTION	1.1
2YXF	X-RAY DIFFRACTION	1.13
8E2Z	X-RAY DIFFRACTION	1.13
7NMR	X-RAY DIFFRACTION	1.15
8ROP	X-RAY DIFFRACTION	1.15
7R7W	X-RAY DIFFRACTION	1.17
4U1M	X-RAY DIFFRACTION	1.18
3CZF	X-RAY DIFFRACTION	1.2
6Y26	X-RAY DIFFRACTION	1.2
7NMC	X-RAY DIFFRACTION	1.2
7NMO	X-RAY DIFFRACTION	1.2
7NMT	X-RAY DIFFRACTION	1.2
6MT3	X-RAY DIFFRACTION	1.21
8EC5	X-RAY DIFFRACTION	1.22
4RMT	X-RAY DIFFRACTION	1.24
7NN5	X-RAY DIFFRACTION	1.24
3IB4	X-RAY DIFFRACTION	1.25
6Y2A	X-RAY DIFFRACTION	1.25
7NMY	X-RAY DIFFRACTION	1.25
7TUC	X-RAY DIFFRACTION	1.25
6V2O	X-RAY DIFFRACTION	1.27
6Y29	X-RAY DIFFRACTION	1.28
7WJ2	X-RAY DIFFRACTION	1.28
3LN4	X-RAY DIFFRACTION	1.3
3BWA	X-RAY DIFFRACTION	1.3
3D25	X-RAY DIFFRACTION	1.3
3MRG	X-RAY DIFFRACTION	1.3
3SPV	X-RAY DIFFRACTION	1.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61769-F1	94.43	0.85

Antibody-complex structures (SAbDab): 44 — 1W72, 2X89, 3GJF, 3HAE, 4KDT, 4WUU, 5WHK, 6FGB, 6ID4, 6NHA, 6UJ9, 6V7Y, 6V7Z, 6V80, 6W51, 7BBG, 7BH8, 7RE7, 7STF, 7T0L, 7TR4, 8EB2, 8EK5, 8FJA, 8FJB (+19 more)

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 22

Disulfide bonds (1): 45–100

Glycosylation sites (7): 111, 114, 21, 39, 61, 68, 78

Mutagenesis-validated functional residues (3):

Position	Phenotype
79	increases tendency towards amyloid formation.
80	decreases tendency towards amyloid formation.
80	increases tendency towards amyloid formation.

Function

Pathways and Gene Ontology

Reactome pathways

32 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236977	Endosomal/Vacuolar pathway
R-HSA-164940	Nef mediated downregulation of MHC class I complex cell surface expression
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127	DAP12 interactions
R-HSA-2424491	DAP12 signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-877300	Interferon gamma signaling
R-HSA-9637628	Modulation by Mtb of host immune system
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-977225	Amyloid fiber formation
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-164938	Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-164952	The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-913531	Interferon Signaling
R-HSA-9635486	Infection with Mycobacterium tuberculosis
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824439	Bacterial Infection Pathways

MSigDB gene sets: 767 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_MEMBRANE_DEPOLARIZATION, SHEPARD_BMYB_MORPHOLINO_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_COGNITION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS

GO Biological Process (38): T cell mediated cytotoxicity (GO:0001913), positive regulation of T cell mediated cytotoxicity (GO:0001916), response to molecule of bacterial origin (GO:0002237), antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent (GO:0002481), peptide antigen assembly with MHC class I protein complex (GO:0002502), peptide antigen assembly with MHC class II protein complex (GO:0002503), positive regulation of T cell cytokine production (GO:0002726), intracellular iron ion homeostasis (GO:0006879), sensory perception of smell (GO:0007608), learning or memory (GO:0007611), negative regulation of neuron projection development (GO:0010977), antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0019885), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), T cell differentiation in thymus (GO:0033077), transferrin transport (GO:0033572), regulation of iron ion transport (GO:0034756), negative regulation of iron ion transport (GO:0034757), protein refolding (GO:0042026), regulation of erythrocyte differentiation (GO:0045646), positive regulation of receptor-mediated endocytosis (GO:0048260), negative regulation of receptor-mediated endocytosis (GO:0048261), negative regulation of epithelial cell proliferation (GO:0050680), negative regulation of neurogenesis (GO:0050768), positive regulation of immune response (GO:0050778), positive regulation of T cell activation (GO:0050870), protein homotetramerization (GO:0051289), multicellular organismal-level iron ion homeostasis (GO:0060586), cellular response to iron ion (GO:0071281), cellular response to iron(III) ion (GO:0071283), cellular response to nicotine (GO:0071316), amyloid fibril formation (GO:1990000), positive regulation of cellular senescence (GO:2000774), negative regulation of forebrain neuron differentiation (GO:2000978), immune system process (GO:0002376), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), iron ion transport (GO:0006826), immune response (GO:0006955), response to metal ion (GO:0010038)

GO Molecular Function (6): structural molecule activity (GO:0005198), MHC class II protein complex binding (GO:0023026), peptide antigen binding (GO:0042605), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (26): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), early endosome lumen (GO:0031905), specific granule lumen (GO:0035580), MHC class I protein complex (GO:0042612), MHC class II protein complex (GO:0042613), MHC class I peptide loading complex (GO:0042824), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), HFE-transferrin receptor complex (GO:1990712), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
Innate Immune System	2
Class I MHC mediated antigen processing & presentation	2
Immune System	2
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1
Adaptive Immune System	1
DAP12 interactions	1
Interferon Signaling	1
Infection with Mycobacterium tuberculosis	1
SARS-CoV-2-host interactions	1
Metabolism of proteins	1
Viral Infection Pathways	1
HIV Infection	1
The role of Nef in HIV-1 replication and disease pathogenesis	1
Host Interactions of HIV factors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
iron ion transport	3
cellular anatomical structure	3
cytoplasm	3
positive regulation of T cell mediated immunity	2
antigen processing and presentation of peptide antigen via MHC class I	2
peptide antigen assembly with MHC protein complex	2
antigen processing and presentation of peptide antigen via MHC class II	2
endomembrane system	2
intracellular membrane-bounded organelle	2
early endosome	2
endosome membrane	2
MHC protein complex	2
leukocyte mediated cytotoxicity	1
T cell mediated immunity	1
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
response to bacterium	1
response to external biotic stimulus	1
antigen processing and presentation of exogenous peptide antigen via MHC class Ib	1
MHC class I protein complex assembly	1
MHC class II protein complex assembly	1
T cell cytokine production	1
positive regulation of cytokine production involved in immune response	1
regulation of T cell cytokine production	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
sensory perception of chemical stimulus	1
behavior	1
cognition	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
antigen processing and presentation of endogenous peptide antigen	1
antigen processing and presentation of exogenous peptide antigen	1
T cell differentiation	1
protein transport	1
regulation of metal ion transport	1
regulation of iron ion transport	1
negative regulation of monoatomic ion transport	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

269 interactions, top by confidence:

A	B	Type	Score
B2M	B2M	psi-mi:“MI:0407”(direct interaction)	0.980
B2M	B2M	psi-mi:“MI:0195”(covalent binding)	0.980
HLA-B	B2M	psi-mi:“MI:0915”(physical association)	0.930

BioGRID (146): B2M (Reconstituted Complex), B2M (Affinity Capture-MS), B2M (Affinity Capture-MS), B2M (Affinity Capture-MS), B2M (Affinity Capture-MS), B2M (Affinity Capture-MS), B2M (Synthetic Growth Defect), B2M (Two-hybrid), B2M (Co-localization), B2M (Affinity Capture-MS), RGPD2 (Affinity Capture-MS), FCGRT (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), DLGAP5 (Affinity Capture-MS), TPST1 (Affinity Capture-MS)

ESM2 similar proteins: O42197, O77517, O77518, O77519, O77520, O77521, O77523, O77524, O77525, O77526, O77528, O77529, O77530, O77531, O77533, O77534, O77535, O77536, O77537, P07151, P16213, P55076, P55079, P61769, P61770, P61771, P63060, P63061, P63062, P63063, P63064, P63065, P63066, P63067, P63068, P63069, P63070, P63071, Q03422, Q04475

Diamond homologs: O42197, O77517, O77518, O77519, O77520, O77521, O77523, O77524, O77525, O77526, O77528, O77529, O77530, O77531, O77532, O77533, O77534, O77535, O77536, O77537, P01844, P01885, P01886, P01887, P01888, P01906, P01910, P04227, P04228, P04440, P07151, P14434, P14435, P14436, P14437, P14438, P15981, P16213, P19341, P20036

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
USF1	“up-regulates quantity by expression”	B2M	“transcriptional regulation”
USF2	“up-regulates quantity by expression”	B2M	“transcriptional regulation”
RELA	“up-regulates quantity by expression”	B2M	“transcriptional regulation”
NfKb-p65/p50	“up-regulates quantity by expression”	B2M	“transcriptional regulation”
B2M	“form complex”	“Class I MHC”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	8	78.8×	2e-11
ER-Phagosome pathway	8	25.9×	5e-08
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	11	24.0×	7e-11
Interferon alpha/beta signaling	6	22.8×	1e-05
Interferon gamma signaling	6	18.8×	4e-05
SARS-CoV-2 activates/modulates innate and adaptive immune responses	8	17.8×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of T cell mediated cytotoxicity	10	113.5×	2e-16
adaptive immune response	8	15.0×	3e-06
immune response	14	14.6×	5e-11

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 7 cancer types — CESC, DLBCLNOS, HNSC, MEL, MLYM, NHL, NSCLC.

Clinical variants and AI predictions

ClinVar

104 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	39
Likely benign	33
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2824511	NM_004048.4(B2M):c.20T>A (p.Leu7Ter)	Pathogenic
31907	NM_004048.4(B2M):c.286G>A (p.Asp96Asn)	Pathogenic
217869	NM_004048.4(B2M):c.67+1G>T	Likely pathogenic
3577174	NM_004048.4(B2M):c.2T>C (p.Met1Thr)	Likely pathogenic
4808285	NM_004048.4(B2M):c.68-2A>C	Likely pathogenic

SpliceAI

402 predictions. Top by Δscore:

Variant	Effect	Δscore
15:44711612:GC:G	donor_gain	1.0000
15:44711614:G:GG	donor_gain	1.0000
15:44715418:CTCA:C	acceptor_loss	1.0000
15:44715419:TCA:T	acceptor_loss	1.0000
15:44715420:CAG:C	acceptor_loss	1.0000
15:44715421:A:AC	acceptor_loss	1.0000
15:44715641:GA:G	donor_gain	1.0000
15:44715693:T:G	donor_gain	1.0000
15:44715697:GTGGG:G	donor_gain	1.0000
15:44715699:GGG:G	donor_gain	1.0000
15:44715700:GG:G	donor_gain	1.0000
15:44715700:GGG:G	donor_gain	1.0000
15:44715701:GG:G	donor_gain	1.0000
15:44716313:A:AG	acceptor_gain	1.0000
15:44716313:ACT:A	acceptor_gain	1.0000
15:44716314:C:G	acceptor_gain	1.0000
15:44716315:T:A	acceptor_gain	1.0000
15:44716326:T:G	acceptor_gain	1.0000
15:44716327:A:AG	acceptor_gain	1.0000
15:44716328:G:GG	acceptor_gain	1.0000
15:44716328:GA:G	acceptor_gain	1.0000
15:44716328:GATC:G	acceptor_gain	1.0000
15:44716355:AGGT:A	donor_loss	1.0000
15:44716356:GGT:G	donor_loss	1.0000
15:44716357:G:T	donor_loss	1.0000
15:44716358:T:A	donor_loss	1.0000
15:44717601:TTTCA:T	acceptor_loss	1.0000
15:44717602:TTCA:T	acceptor_loss	1.0000
15:44717603:TCA:T	acceptor_loss	1.0000
15:44717604:CAG:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000219847 (15:44712011 C>T), RS1000272307 (15:44711761 G>A,C), RS1000540082 (15:44717506 T>C), RS1000606334 (15:44710366 A>G), RS1000996352 (15:44711811 C>A,T), RS1001671393 (15:44714931 T>A), RS1001988503 (15:44713070 A>G), RS1001996727 (15:44713468 C>A), RS1002553374 (15:44714300 A>G), RS1002617998 (15:44715854 G>A), RS1002665848 (15:44716125 A>C,G,T), RS1002672364 (15:44716446 G>C,T), RS1004444280 (15:44712535 G>T), RS1004630351 (15:44712734 T>C,G), RS1004777040 (15:44711100 A>G)

Disease associations

OMIM: gene MIM:109700 | disease phenotypes: MIM:241600, MIM:105200, MIM:620659, MIM:604360

GenCC curated gene-disease

Disease	Classification	Inheritance
hypoproteinemia, hypercatabolic	Strong	Autosomal recessive
variant ABeta2M amyloidosis	Strong	Autosomal dominant
MHC class I deficiency	Supportive	Autosomal recessive
familial visceral amyloidosis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypoproteinemia, hypercatabolic	Limited	AR

Mondo (7): hypoproteinemia, hypercatabolic (MONDO:0009434), familial visceral amyloidosis (MONDO:0007099), amyloidosis, hereditary systemic 6 (MONDO:0971010), non-Hodgkin lymphoma (MONDO:0018908), hereditary spastic paraplegia 11 (MONDO:0011445), variant ABeta2M amyloidosis (MONDO:0017810), MHC class I deficiency (MONDO:0011476)

Orphanet (3): Hereditary amyloidosis with primary renal involvement (Orphanet:85450), Non-Hodgkin lymphoma (Orphanet:547), Autosomal recessive spastic paraplegia type 11 (Orphanet:2822)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000157	Abnormality of the tongue
HP:0000969	Edema
HP:0001271	Polyneuropathy
HP:0001278	Orthostatic hypotension
HP:0001482	Subcutaneous nodule
HP:0001824	Weight loss
HP:0001917	Renal amyloidosis
HP:0002028	Chronic diarrhea
HP:0002094	Dyspnea
HP:0002110	Bronchiectasis
HP:0002176	Spinal cord compression
HP:0002205	Recurrent respiratory infections
HP:0002756	Pathologic fracture
HP:0002986	Radial bowing
HP:0003022	Hypoplasia of the ulna
HP:0003073	Hypoalbuminemia
HP:0003075	Hypoproteinemia
HP:0003365	Arthralgia of the hip
HP:0003621	Juvenile onset
HP:0004315	Decreased circulating IgG concentration
HP:0005244	Gastrointestinal infarctions
HP:0007141	Sensorimotor neuropathy
HP:0010286	Abnormal salivary gland morphology
HP:0010976	Decreased total B cell count
HP:0011805	Abnormal skeletal muscle morphology
HP:0011915	Cardiovascular calcification
HP:0012065	Multiple bony cystic lesions
HP:0012185	Constrictive median neuropathy

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008228	Lymphoma, Non-Hodgkin	C04.557.386.480; C15.604.515.569.480; C20.683.515.761.480
C538249	Amyloidosis, familial visceral (supp.)
C565476	Hypoproteinemia, Hypercatabolic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1741302 (SINGLE PROTEIN), CHEMBL5465401 (PROTEIN COMPLEX)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
B2M S14FS	Pembrolizumab	Skin Melanoma	Resistance	CIViC C	EID1569

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

1 measured of 5 human assays (7 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(4S,4aR,5S,5aS,12aS)-4-(dimethylamino)-5,10,12a-trihydroxy-1,3,11,12-tetraketo-6-methylene-4a,5,5a,11a-tetrahydro-4H-tetracene-2-carboxamide;hydrochloride	IC50	122000 nM

CTD chemical–gene interactions

104 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Cadmium	affects secretion, increases expression, increases secretion, increases abundance, affects reaction	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	increases abundance, decreases expression, affects expression	3
Arsenic	increases expression, increases abundance, increases secretion, decreases expression	3
Metribolone	increases secretion, decreases reaction, increases expression	3
bisphenol A	affects expression, increases expression	2
sodium arsenite	decreases expression, increases abundance	2
chloropicrin	affects expression, decreases expression	2
Decitabine	affects expression, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants, Occupational	increases expression	2
Copper	affects binding, decreases folding, decreases stability, increases reaction	2
Estradiol	decreases expression, increases expression	2
Ifosfamide	increases expression	2
Lead	affects expression, increases abundance, increases secretion	2
Nickel	increases expression	2
Ozone	affects expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	decreases expression, increases expression	2
Smoke	increases abundance, decreases expression	2
Dihydrotestosterone	increases expression, decreases reaction	2
Tretinoin	increases expression	2
bisphenol F	increases expression	1
shuanghuang shengbai	increases expression	1
napabucasin	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650979	Binding	Binding affinity to human B2M incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

205 cell lines: 162 cancer cell line, 17 spontaneously immortalized cell line, 17 induced pluripotent stem cell, 6 embryonic stem cell, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0008	Daudi	Cancer cell line	Male
CVCL_0248	DLD-1	Cancer cell line	Male
CVCL_0292	HCT 15	Cancer cell line	Male
CVCL_0399	LoVo	Cancer cell line	Male
CVCL_1514	NCI-H2009	Cancer cell line	Female
CVCL_1533	NCI-H2135	Cancer cell line	Sex unspecified
CVCL_1550	NCI-H2347	Cancer cell line	Female
CVCL_1616	OC 314	Cancer cell line	Female
CVCL_1618	OC 316	Cancer cell line	Female
CVCL_1707	SNG-M	Cancer cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00090038	PHASE4	COMPLETED	Effect of Rituximab on Immunological Recall Response to Specific Antigens in the Treatment of Non-Hodgkin’s Lymphoma
NCT00162955	PHASE4	COMPLETED	Prevention of CHOP-induced Chronic Cardiotoxicity
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00430352	PHASE4	COMPLETED	MAXIMA Study: A Study of Maintenance Therapy With MabThera (Rituximab) in Patients With Non-Hodgkin’s Lymphoma.
NCT00797810	PHASE4	UNKNOWN	Intensification Therapy of Mature B-ALL, Burkitt and Burkitt Like and Other High Grade Non-Hodgkin’s Lymphoma in Adults
NCT00808171	PHASE4	COMPLETED	Evaluation of the Analgesy With Emla and/or Nitrous Oxide in Pediatric Patients for Lumbar Puncture
NCT00926757	PHASE4	COMPLETED	Prophylactic Use of Entecavir for Non-Hodgkin’s Lymphoma Patients With Resolved Hepatitis B
NCT00969462	PHASE4	COMPLETED	Doxorubicin Pharmacokinetics and Response in Non Hodgkin’s Lymphoma
NCT01124526	PHASE4	COMPLETED	Efficacy Response Duration and Toxicity of Rituximab, Fludarabine, and Cyclophosphamide (RFC) as 1st Line Treatment and Rituximab (R) in Maintenance Treatment in Follicular Non Hodgkin (FNH) Lymphoma
NCT01164475	PHASE4	COMPLETED	Evaluation of Approved Weight-Based Dose Compared to Fixed Dose of Plerixafor in Patients With Non-Hodgkin’s Lymphoma (NHL) Weighing Less Than 70 Kilograms
NCT01180049	PHASE4	COMPLETED	Comparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma
NCT02782845	PHASE4	COMPLETED	An Expanded Access Program of Pegfilgrastim (Neulastim) in Participants With Non-Hodgkin’s Lymphoma (NHL)
NCT05191225	PHASE4	UNKNOWN	Ultrafast Truxima Infusion in Non-Hodgkin’s Lymphoma: Txagorapid Study
NCT06665737	PHASE4	NOT_YET_RECRUITING	Outcomes of Early and Late Administration G-CSF for Primary Prophylaxis in Non-Hodgkin’s Lymphoma Patients
NCT06876649	PHASE4	RECRUITING	A Master Protocol to Evaluate the Long-Term Safety of (LY3527727) Pirtobrutinib
NCT06876662	PHASE4	RECRUITING	A Study of (LY3527727) Pirtobrutinib in Participants With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00057343	PHASE3	TERMINATED	Safety and Efficacy of Zevalin in the Treatment of Non-Hodgkin’s Lymphoma
NCT00078598	PHASE3	UNKNOWN	A Study of Rituximab Versus Iodine I 131 Tositumomab Therapy for Patients With Non-Hodgkin’s Lymphoma
NCT00091676	PHASE3	UNKNOWN	Study of the BiovaxId Tumor Derived Idiotype Vaccine in Patients With Follicular Lymphoma
NCT00129090	PHASE3	COMPLETED	Mega-CHOEP: Conventional Chemo Vs HD Chemo Followed by Auto SCT in Younger Pts With Aggressive Non-Hodgkin’s Lymphoma
NCT00133302	PHASE3	TERMINATED	Study of Standard CHOP Versus Biweekly CHOP in Aggressive Non-Hodgkin’s Lymphoma (JCOG9809)
NCT00139841	PHASE3	COMPLETED	Safety and Efficacy of Treanda™ (Bendamustine HCl) in Patients With Indolent Non-Hodgkin’s Lymphoma (NHL) Who Are Refractory to Rituximab
NCT00145652	PHASE3	COMPLETED	Adjuvant I.V. Iron Therapy During Erythropoetin Treatment of Anemic Patients With Lymphoproliferative Disorders.
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00269113	PHASE3	COMPLETED	A Study of MabThera (Rituximab) in Patients With Advanced Non-Hodgkin’s Lymphoma
NCT00312845	PHASE3	COMPLETED	Study of VELCADE and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma
NCT00332202	PHASE3	COMPLETED	PRELUDE:Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastaurin
NCT00352846	PHASE3	COMPLETED	Effect of Zoledronic Acid on Chemotherapy Induced Bone Loss
NCT00398411	PHASE3	COMPLETED	Moxifloxacin in the Prevention of Bacteremia After High-dose Chemotherapy and Transplantation of Peripheral Stem Cells
NCT00463463	PHASE3	UNKNOWN	Zevalin and BEAM High-dose Chemotherapy Compared With BEAM Alone as Conditioning Regimen in Patients With Chemosensitive Relapse of Non-Hodgkin’s Lymphoma
NCT00491491	PHASE3	COMPLETED	Zevalin-beam for Aggressive Lymphoma
NCT00577161	PHASE3	WITHDRAWN	Fludarabine, Pixantrone and Rituximab vs Fludarabine and Rituximab forRelapsed or Refractory Indolent NHL
NCT00719472	PHASE3	COMPLETED	A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin’s Lymphoma (RATE)
NCT00877006	PHASE3	COMPLETED	Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With R-CVP or R-CHOP in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL) - Referred to as the BRIGHT Study
NCT00877214	PHASE3	ACTIVE_NOT_RECRUITING	Significance of Duration of Maintenance Therapy With Rituximab in Non-Hodgkin Lymphomas
NCT00928018	PHASE3	COMPLETED	Tacrolimus/Sirolimus/Methotrexate vs Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
NCT00991211	PHASE3	COMPLETED	Bendamustine Plus Rituximab Versus CHOP Plus Rituximab