KNL1
KNL1 (Outer kinetochore KNL1 complex subunit KNL1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma, Skin cancer, Colorectal cancer and 4 more.
Overview
Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions. Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules. The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle.
Open Targets scores its association with cancer at 0.66 (direct and indirect evidence; datatypes literature 0.91, genetic association 0.19, somatic mutation 0.84). IntOGen calls it a driver in 3 cohorts (0 activating, 3 loss-of-function), covering Basal Cell Carcinoma, Glioblastoma Multiforme, Hepatocellular Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · KNL1 (Outer kinetochore KNL1 complex subunit KNL1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma, Skin cancer, Colorectal cancer and 4 more.
- 1 · What it is
KNL1 (Outer kinetochore KNL1 complex subunit KNL1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma, Skin cancer, Colorectal cancer and 4 more.
- 2 · What goes wrong in cancer
Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions.
- 3 · How drugs use it
No product in this corpus aims at KNL1 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:24054 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8NG31 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000137812 (association with cancer (MONDO_0004992) 0.66; per-cancer scores at or above 0.5: colorectal cancer 0.54, melanoma 0.52, skin cancer 0.55, breast cancer 0.52 (GraphQL API, CC0)); IntOGen KNL1 (driver in 3 cohorts (Act 0, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions. Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules. The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle. Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore. Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1. Location: Nucleus; Chromosome, centromere, kinetochore; Cytoplasm (UniProt). Locus 15q15.1 (HGNC).
- Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)
- Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)
- Colorectal cancer: Open Targets association 0.54 with colorectal cancer (MONDO_0005575)
- Breast cancer: Open Targets association 0.52 with breast cancer (MONDO_0007254)
- Basal cell carcinoma: IntOGen driver in 1 cohort (BCC)
- Glioma & glioblastoma: IntOGen driver in 1 cohort (GBM)
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 a loss-of-function (LoF) driver in 3 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"KNL1" OR ABSTRACT:"KNL1" OR TITLE:"kinetochore scaffold 1" OR ABSTRACT:"kinetochore scaffold 1" OR TITLE:"Outer kinetochore KNL1 complex subunit KNL1" OR ABSTRACT:"Outer kinetochore KNL1 complex subunit KNL1" OR TITLE:"D40" OR ABSTRACT:"D40" OR TITLE:"AF15Q14" OR ABSTRACT:"AF15Q14" OR TITLE:"CT29" OR ABSTRACT:"CT29") 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 KNL1, not a curated reading list.
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