# KNL1

Source: https://onco.cc/targets/knl1/  
OnCo record `knl1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: kinetochore scaffold 1; Outer kinetochore KNL1 complex subunit KNL1; D40; AF15Q14; CT29; KIAA1570; hKNL-1; hSpc105; PPP1R55; Spc7; MCPH4; CASC5
- Tags: cancer-genes-wave
- Symbol: KNL1
- Class: tumor-suppressor
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:24054: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24054
- UniProt Q8NG31: https://www.uniprot.org/uniprotkb/Q8NG31/entry
- NCBI Gene 57082: https://www.ncbi.nlm.nih.gov/gene/57082
- Ensembl ENSG00000137812: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137812

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Basal cell carcinoma](https://onco.cc/cancers/basal-cell-carcinoma/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Melanoma](https://onco.cc/cancers/melanoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/knl1.json