KLHL14

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.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2013-01-01 : Zhang : DLBCL

Relevance tier by entity

Entity Tier Description
DLBCL 1 high-confidence DLBCL gene1

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity source frequency (%)
DLBCL GAMBL genomes 4.59
DLBCL Schmitz cohort 6.60
DLBCL Reddy cohort 4.60
DLBCL Chapuy cohort 7.26

Mutation pattern and selective pressure estimates

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL No No 0.000 0.000
DLBCL No No 3.154 2.846
FL No No 12.248 24.944

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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

KLHL14 Expression

1.
Zhang J, Grubor V, Love CL, Banerjee A, Richards KL, Mieczkowski PA, Dunphy C, Choi W, Au WY, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers C, Naresh K, Evens A, Gordon LI, Czader M, Gill JI, Hsi ED, Liu Q, Fan A, Walsh K, Jima D, Smith LL, Johnson AJ, Byrd JC, Luftig MA, Ni T, Zhu J, Chadburn A, Levy S, Dunson D, Dave SS. Genetic heterogeneity of diffuse large B-cell lymphoma. Proceedings of the National Academy of Sciences of the United States of America. 2013;110:1398–1403. PMCID: PMC3557051

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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