Table of Contents

Overview

The B2M (β2-microglobulin) gene plays a crucial role in the function of the major histocompatibility complex (MHC) class I molecules, which are essential for immune system recognition of infected or malignant cells.

Experimental Evidence

B2M mutations in B-cell lymphomas, particularly in DLBCL and PMBCL, lead to reduced MHC class I expression, enabling tumor cells to evade immune detection and destruction by cytotoxic T cells. This is often accompanied by mutations in the β2-Microglobulin gene, which further aids in immune evasion.1

Relevance tier by entity

Entity Tier Description
BL 2 Role of B2M mutations in BL requires confirmation
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
MCL 2 Role of B2M mutations in MCL requires confirmation
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 156 0.1433 [0.1224,0.1641]
DLBCL GAMBL with Reddy 2,088 277 0.1327 [0.1181,0.1472]
DLBCL BC 231 29 0.1255 [0.0828,0.1683]
DLBCL Dana-Farber 303 38 0.1254 [0.0881,0.1627]
DLBCL NCI 470 73 0.1553 [0.1226,0.1881]
DLBCL Reddy 999 121 0.1211 [0.1009,0.1414]
DLBCL DLBCL_ICGC 85 16 0.1882 [0.1051,0.2713]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 41 0.0639 [0.0449,0.0828]
FL GAMBL with Crouch 1,189 80 0.0673 [0.053,0.0815]
FL BC 379 22 0.0580 [0.0345,0.0816]
FL Kalmbach 164 6 0.0366 [0.0079,0.0653]
FL Crouch 547 39 0.0713 [0.0497,0.0929]
FL FL_ICGC 99 13 0.1313 [0.0648,0.1978]

MCL

pathology Collection N mutated Incidence CI
MCL GAMBL 160 1 0.0037 [0,0.0131]
MCL BC_MCL 103 1 0.0097 [0,0.0286]
MCL Barcelona 57 0 0.0018 [0,0.0126]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 6 0.0175 [0.0029,0.0321]
BL GAMBL without ICGC/Zhou 320 8 0.0246 [0.0077,0.0416]
BL GAMBL with Panea 410 9 0.0195 [0.0061,0.0329]
BL BLGSP 219 5 0.0228 [0.003,0.0426]
BL Zhou/ICGC 90 1 0.0111 [0,0.0328]
BL Panea 101 3 0.0297 [0,0.0628]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 13.3547 28.5896 0.0069
FL 36.5331 147.2290 0.0000
DLBCL 12.2654 61.8372 0.0000

B2M Hotspots

Chromosome Coordinate (hg19) DLBCL FL BL HGVSp
15 45003745,45003746,45003747 87 11 4 M1?
15 45003778,45003779 33 5 0 L12P
15 45003778,45003779 33 5 0 L12Q
15 45003778,45003779 33 5 0 L12R
15 45003778,45003779 33 5 0 L12*
15 45003763,45003764 35 3 0 L7*
15 45003763,45003764 35 3 0 L7S
15 45003763,45003764 35 3 0 L7V
21 3 2 L15Ffs*41
15 45003768,45003770 7 2 1 V9E
15 45007809,45007810,45007811 9 1 0 Y86H
15 45007809,45007810,45007811 9 1 0 Y86N
15 45003768,45003770 7 2 1 V9G
15 45007809,45007810,45007811 9 1 0 Y86*
15 45003768,45003770 7 2 1 V9L
15 45003768,45003770 7 2 1 V9_A20del
15 45007809,45007810,45007811 9 1 0 Y86D
15 45007809,45007810,45007811 9 1 0 Y86F
15 45007691,45007690 5 1 0 Y46Cfs*10
15 45003782,45003781 6 0 0 L13R
15 45003766,45003767 6 0 0 A8Lfs*36
15 45003766,45003767 6 0 0 A8P
15 45007686,45007687,45007688 4 2 0 C45G
15 45007686,45007687,45007688 4 2 0 C45Y
15 45003782,45003781 6 0 0 L13P
15 45003766,45003767 6 0 0 A8D
15 45003766,45003767 6 0 0 A8T
15 45007686,45007687,45007688 4 2 0 C45R
15 45007686,45007687,45007688 4 2 0 C45W
15 45003782,45003781 6 0 0 L13F
15 45007691,45007690 5 1 0 Y46*
15 45007691,45007690 5 1 0 Y46S
15 45003773 4 0 0 L10R
15 45007845,45007846 4 0 0 Y98N
15 45003773 4 0 0 L10H
15 45007845,45007846 4 0 0 Y98D
15 45007845,45007846 4 0 0 Y98S
15 45003761 3 0 0 A6D
15 45007676,45007674 3 0 0 N41K
15 45003748 3 0 0 S2P
15 45007768,45007767 2 1 0 S72*
15 45007897,45007898,45007896 2 0 1 W115*
15 45007676,45007674 3 0 0 N41H
15 45003748 3 0 0 S2_?4
15 45007768,45007767 2 1 0 S72A
15 45007897,45007898,45007896 2 0 1 W115R
2 0 0 A11Sfs*42
15 45007727 2 0 0 D58E
15 45007681 2 0 0 L43P
2 0 0 S14Ffs*29
2 0 0 Q28Sfs*29
2 0 0 Q28_V29del
15 45007639 0 1 1 V29G
15 45007639 0 1 1 V29Hfs*13
15 45003758 2 0 0 V5Afs*27
15 45003758 2 0 0 V5E
15 45007641 2 0 0 Y30D
15 45007641 2 0 0 Y30H
15 45007770 1 0 0 D73H
1 0 0 G17Ffs*41
15 45007888 1 0 0 I112K
15 45007633 1 0 0 I27N
1 0 0 L74Ffs*14
1 0 0 R101Lfs*15
15 45003751 1 0 0 R3C
0 1 0 S31Vfs*12
1 0 0 S48Wfs*8
Structure with HotMAPS hotspots

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : DLBCL 2012-03-06 : Lohr : DLBCL 2013-01-01 : Zhang : DLBCL 2013-08-15 : Morin : DLBCL 2015-02-12 : Reichel : PMBL 2017-05-01 : Albuquerque : DLBCL 2017-10-10 : Reddy : DLBCL 2018-05-01 : Chapuy : DLBCL 2018-10-01 : Arthur : DLBCL 2020-07-30 : Pararajalingam : MCL 2021-05-05 : Hubschmann : DLBCL

References

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Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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