KLHL14 - morinlab/LLMPP GitHub Wiki
bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @reddyGeneticFunctionalDrivers2017, @zhangGeneticHeterogeneityDiffuse2013, @schmitzGeneticsPathogenesisDiffuse2018,
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).[@zhangGeneticHeterogeneityDiffuse2013] 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.[@schmitzGeneticsPathogenesisDiffuse2018] KLHL14 loss has been shown to BCR-dependent NF-κB activation and cell survival in DLBCL.[@schmitzGeneticsPathogenesisDiffuse2018] 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).[@choiRegulationCellReceptordependent2020]
Relevance tier by entity
include:tables/table1_KLHL14.md
Mutation incidence in large patient cohorts (GAMBL reanalysis)
DLBCL
include:tables/DLBCL_KLHL14.md
Mutation pattern and selective pressure estimates
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 |
include:tables/browser_KLHL14.md
include:tables/mermaid_KLHL14.md