{"entity":{"id":"klhl6","kind":"target","name":"KLHL6","aka":["kelch like family member 6","Kelch-like protein 6","FLJ00029"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:18653","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18653"},{"label":"UniProt Q8WZ60","url":"https://www.uniprot.org/uniprotkb/Q8WZ60/entry"},{"label":"NCBI Gene 89857","url":"https://www.ncbi.nlm.nih.gov/gene/89857"},{"label":"Ensembl ENSG00000172578","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172578"}],"tags":["cancer-genes-wave"],"related":["civic","intogen"],"cancers":["non-hodgkin-lymphoma","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"KLHL6","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:18653","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18653","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q8WZ60","url":"https://www.uniprot.org/uniprotkb/Q8WZ60/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KLHL6","url":"https://civicdb.org/features/16661","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen KLHL6","url":"https://www.intogen.org/search?gene=KLHL6","note":"driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:18653","ensembl":"ENSG00000172578","uniprot":"Q8WZ60","entrez":"89857","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).","whereFound":["Non-Hodgkin lymphoma: IntOGen driver in 2 cohorts (MLYM, NHL)","Diffuse large B-cell lymphoma: CIViC evidence names this disease"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/klhl6/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}]}}