KNL1: Kinetochore Scaffold 1
Essential component of the kinetochore complex for chromosome segregation
Gene Information Card
| Symbol | KNL1 |
|---|---|
| Full Name | Kinetochore Scaffold 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 57082 ncbi.nlm.nih.gov/gene/57082 |
| Ensembl ID | ENSG00000111846 |
| UniProt ID | Q8NG31 |
| OMIM ID | 609173 |
| HGNC ID | 24054 |
| Aliases | CASC5, AF15q14, D40, KIAA1570, MCPH4, PPP1R55, SLK, Spc105 |
Description
KNL1 encodes a kinetochore scaffold protein that is essential for proper chromosome segregation during mitosis. It serves as a platform for recruiting other kinetochore components, including the MIS12 complex and the NDC80 complex, and is involved in spindle checkpoint signaling. Mutations in KNL1 cause autosomal recessive primary microcephaly type 4 (MCPH4).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary microcephaly 4 (MCPH4) | Loss-of-function mutations impair kinetochore assembly, leading to mitotic errors and reduced neuronal progenitor cell proliferation | OMIM #609173; PMID: 18674748 |
| Breast cancer | Somatic mutations and altered expression may contribute to chromosomal instability | COSMIC; PMID: 22980975 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.2 | Medium |
| Lymph node | 6.1 | Low |
| Brain | 4.3 | Low |
| Ovary | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | High expression; commonly used in mitotic studies |
| HEK 293 | 10.1 | Moderate expression |
| K562 | 8.7 | Moderate expression |
| MCF7 | 6.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.6125G>A (p.Arg2042Gln) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.5095C>T (p.Arg1699*) | Nonsense | <0.01% | Loss of function; associated with MCPH4 |
| c.4348C>T (p.Arg1450*) | Nonsense | <0.01% | Loss of function; associated with MCPH4 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in KNL1 lead to truncated proteins, causing primary microcephaly due to impaired kinetochore function and mitotic defects.
Gain of Function (GOF)
No documented gain-of-function mutations in KNL1.
Dominant Negative (DN)
No evidence of dominant-negative effects; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • kinetochore | • chromosome segregation |
| • mitotic spindle checkpoint | • protein binding |
| • microtubule binding |
Pathways
• Cell cycle - Kinetochore assembly
• Mitotic spindle checkpoint
• Chromosome segregation
Protein Summary
KNL1 is a 2342-amino acid protein that localizes to the kinetochore during mitosis. It contains multiple repeat motifs that mediate interactions with other kinetochore proteins, including ZWINT and the MIS12 complex. KNL1 is essential for the spindle assembly checkpoint and accurate chromosome segregation. Its N-terminal region binds protein phosphatase 1 (PP1), regulating kinetochore-microtubule attachments.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KNL1 Knockout HEK293 Cell Line | EDJ-KQ13967 | Human | 57082 | Details Get a Quote |
| KNL1 Knockout A-549 Cell Line | EDJ-KQ43901 | Human | 57082 | Details Get a Quote |
| KNL1 Knockout HCT 116 Cell Line | EDJ-KQ43902 | Human | 57082 | Details Get a Quote |
| KNL1 Knockout HeLa Cell Line | EDJ-KQ43903 | Human | 57082 | Details Get a Quote |
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