HNRNPU

Overview

HNRNPU is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Mutations in HNRNPU are haploinsufficient and significantly alter the transcriptome of MYC-driven lymphomas. These mutations were found in a notable percentage of high-grade B-cell lymphomas with double-hit BCL2 translocations (HGBL-DH-BCL2) and Burkitt lymphoma (BL).¹

Relevance tier by entity

Entity	Tier	Description
BL	1-a	aSHM target and high-confidence BL gene
DLBCL	1-a	aSHM target and high-confidence DLBCL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	5.77
BL	Thomas cohort	6.40
BL	Panea cohort	8.90
DLBCL	GAMBL genomes	2.49
DLBCL	Schmitz cohort	3.40
DLBCL	Reddy cohort	2.40
DLBCL	Chapuy cohort	3.42

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	Yes	1.081	27.052
DLBCL	Yes	No	1.712	0.000
FL	Yes	No	4.865	31.056

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr1	245023502	245029083	TSS	NA

[!NOTE] First described in BL in 2019 by Panea RI

## HNRNPU Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr1	245027102	G>A	Q170*
chr1	245027099	G>C	Q171E
chr1	245027099	G>A	Q171*

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

1. Qureshi, Q., Coyle, K., Thomas, N., Collinge, B., Dreval, K., Hilton, L., Wong, J., Scott, D., Audas, T., & Morin, R. (2023). Hnrnpu mutations Are Haploinsufficient and Alter the Transcriptome of MYC-Driven Lymphomas. Blood. https://doi.org/10.1182/blood-2023-190409.