Table of Contents

Overview

Mutations in GNA13, which encodes a G protein alpha subunit involved in multiple signaling pathways, have been identified as significant contributors to the pathogenesis of germinal centre-derived B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).1 This gene has some recurrent sites of mutations (hot spots). Overall, mutations are often loss-of-function in nature, disrupting the normal activity of GNA13. GNA13 regulates B-cell homing and growth suppression within the germinal center niche and its loss of function promotes lymphoma development.2

Experimental Evidence

Driver mutations affecting this gene in BL/FL/DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).3,4

Relevance tier by entity

Entity Tier Description
BL 1 High-confidence BL gene
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
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 1,089 118 0.1084 [0.0899,0.1268]
DLBCL GAMBL with Reddy 2,088 237 0.1135 [0.0999,0.1271]
DLBCL BC 231 30 0.1299 [0.0865,0.1732]
DLBCL Dana-Farber 303 34 0.1122 [0.0767,0.1478]
DLBCL NCI 470 40 0.0851 [0.0599,0.1103]
DLBCL Reddy 999 119 0.1191 [0.099,0.1392]
DLBCL DLBCL_ICGC 85 14 0.1647 [0.0859,0.2436]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 55 0.0857 [0.064,0.1073]
FL GAMBL with Crouch 1,189 115 0.0967 [0.0799,0.1135]
FL BC 379 37 0.0976 [0.0677,0.1275]
FL Kalmbach 164 12 0.0732 [0.0333,0.113]
FL Crouch 547 60 0.1097 [0.0835,0.1359]
FL FL_ICGC 99 6 0.0606 [0.0136,0.1076]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 60 0.1941 [0.15,0.2382]
BL GAMBL without ICGC/Zhou 320 64 0.1999 [0.1561,0.2437]
BL GAMBL with Panea 410 81 0.1974 [0.1589,0.2359]
BL BLGSP 219 43 0.1963 [0.1437,0.249]
BL Zhou/ICGC 90 17 0.1889 [0.108,0.2698]
BL Panea 101 21 0.2079 [0.1288,0.2871]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 34.0099 620.1945 0
FL 33.6636 72.2831 0
DLBCL 6.2235 32.1549 0

GNA13 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr17 63052633 G>A Q27*
chr17 63052631 C>G Q27H
chr17 63052630 G>A Q28*
chr17 63052613 C>G E33D
chr17 63052609 C>G D35H

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 : FL 2012-12-01 : Love : BL 2015-02-12 : Reichel : PMBL

References

1.
Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, Liu Y, Gaiolla R, Eng K, Brody J, Inghirami G, Carlo-Stella C, Santoro A, Rahal D, Totonchy J, Elemento O, Cesarman E, Roshal M. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood. 2015 Feb 12;125(7):1061–1072.
2.
Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561
3.
Muppidi J, Schmitz R, Green JA, Green JA, Xiao W, Larsen AB, Braun S, An J, Xu Y, Rosenwald A, Ott G, Gascoyne R, Rimsza L, Campo E, Jaffe E, Delabie J, Smeland E, Braziel R, Tubbs R, Cook J, Weisenburger D, Chan W, Vaidehi N, Staudt L, Cyster J. Loss of signaling via Gα13 in germinal center B cell-derived lymphoma. Nature. 2014;516:254–258.
4.
O’Hayre M, Inoue A, Kufareva I, Wang Z, Mikelis CM, Drummond RA, Avino S, Finkel K, Kalim KW, DiPasquale G, Guo F, Aoki J, Zheng Y, Lionakis MS, Molinolo AA, Gutkind JS. Inactivating mutations in GNA13 and RHOA in Burkitt’s lymphoma and diffuse large B-cell lymphoma: A tumor suppressor function for the Gα13/RhoA axis in B cells. Oncogene. 2016 Jul 21;35(29):3771–3780. PMCID: PMC4885800
5.
Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJM, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298–303. PMCID: PMC3210554

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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