KLHL14

Table of Contents

Overview
Experimental Evidence
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
- DLBCL
Mutation pattern and selective pressure estimates
Expression
KLHL14 Hotspots

Overview

KLHL14 (Kelch-like family member 14) is a gene that has been identified as playing a role in B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL).¹ KLHL14 has been identified as a recurrent target of somatic mutations in ABC DLBCLs. These mutations are a feature of the MCD genetic subgroup of DLBCL. The gene encodes a protein involved in the ubiquitin-proteasome system, and its inactivation leads to increased cell proliferation and survival, suggesting its role as a tumor suppressor.² KLHL14 loss has been shown to BCR-dependent NF-κB activation and cell survival in DLBCL.² This gene has some mutation hotspots but the patter of mutation overall is consistent with its role as a tumor suppressor gene.

Experimental Evidence

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

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

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Mutation pattern and selective pressure estimates

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Expression

KLHL14 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr18	30349909	G>A	L216F
chr18	30349905	T>G	N217T
chr18	30349902	A>C	F218C
chr18	30349882	G>C	L225V

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Choi J, Phelan JD, Wright GW, Häupl B, Huang DW, Shaffer AL, Young RM, Wang Z, Zhao H, Yu X, Oellerich T, Staudt LM. Regulation of B cell receptor-dependent NF-κB signaling by the tumor suppressor KLHL14. Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6092–6102. PMCID: PMC7084139

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