# KLHL6

Source: https://onco.cc/targets/klhl6/  
OnCo record `klhl6` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KLHL6 (Kelch-like protein 6) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma and Diffuse large B-cell lymphoma.

## Summary

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a multifunctional regulator of B-cell receptor (BCR) signalling, germinal centre formation, and T-cell function. Functions by mediating polyubiquitination of target proteins, leading to their proteasomal degradation. In B-cells, plays an essential role in BCR signalling and germinal centre B-cell maturation.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. IntOGen calls it a driver in 2 cohorts (1 activating, 1 loss-of-function), covering Malignant Lymphoma, Non-Hodgkin Lymphoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: kelch like family member 6; Kelch-like protein 6; FLJ00029
- Tags: cancer-genes-wave
- Symbol: KLHL6
- Class: tumor-suppressor
- Biology: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a multifunctional regulator of B-cell receptor (BCR) signalling, germinal centre formation, and T-cell function. Functions by mediating polyubiquitination of target proteins, leading to their proteasomal degradation. In B-cells, plays an essential role in BCR signalling and germinal centre B-cell maturation. Targets the BCR signalling subunits CD79A and CD79B for ubiquitin-mediated degradation, thereby controlling surface BCR homeostasis. Mediates polyubiquitination and degradation of the mRNA decay factor roquin-2/RC3H2, which in turn allows accumulation of TNFAIP3, a negative regulator of NF-kappa-B signalling, thereby providing feedback inhibition of BCR-induced NF-kappa-B activation. In T-cells, acts as a dual negative regulator of T-cell exhaustion and mitochondrial dysfunction. Location: Cytoplasm (UniProt). Locus 3q27.1 (HGNC).
- Where found: Non-Hodgkin lymphoma: IntOGen driver in 2 cohorts (MLYM, NHL); Diffuse large B-cell lymphoma: CIViC evidence names this disease

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 1 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:18653: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18653
- UniProt Q8WZ60: https://www.uniprot.org/uniprotkb/Q8WZ60/entry
- NCBI Gene 89857: https://www.ncbi.nlm.nih.gov/gene/89857
- Ensembl ENSG00000172578: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172578

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)

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JSON: https://onco.cc/api/v1/entities/klhl6.json