KLHL6
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at KLHL6 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:18653 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8WZ60 (protein name, function text, keywords and locations (REST API)); CIViC gene KLHL6 (1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); IntOGen KLHL6 (driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- Non-Hodgkin lymphoma: IntOGen driver in 2 cohorts (MLYM, NHL)
- Diffuse large B-cell lymphoma: CIViC evidence names this disease
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"KLHL6" OR ABSTRACT:"KLHL6" OR TITLE:"kelch like family member 6" OR ABSTRACT:"kelch like family member 6" OR TITLE:"Kelch-like protein 6" OR ABSTRACT:"Kelch-like protein 6" OR TITLE:"FLJ00029" OR ABSTRACT:"FLJ00029") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about KLHL6, not a curated reading list.