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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KNL1
kinetochore scaffold 1
Chromosome 15 Β· 15q15.1
NCBI Gene: 57082Ensembl: ENSG00000137812.21HGNC: HGNC:24054UniProt: Q8NG31
120PubMed Papers
21Diseases
0Drugs
22Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein localization to kinetochoreprotein bindingmicrotubule bindingmitotic sister chromatid segregationautosomal recessive primary microcephalygenetic disorderPrimary microcephalyEndometrial Endometrioid Adenocarcinoma
✦AI Summary

KNL1 (kinetochore scaffold 1) is an evolutionarily conserved outer kinetochore protein essential for accurate chromosome 15. As a key component of the KMN network, KNL1 serves as a multifunctional docking platform that mediates microtubule-kinetochore interactions and recruits spindle assembly checkpoint (SAC) components 12. KNL1 directly recruits MAD2L1, BUB1, and BUB1B to unattached kinetochores, with the KNL1-Bub3-Bub1 pathway essential for SAC activation when kinetochores are misaligned 3. The protein contains multiple interaction motifs (RVSF, SILK, MELT, KI) that facilitate recruitment and regulation of checkpoint proteins, and it coordinates with CENPK to recruit the NDC80 complex 1. KNL1 can bind either microtubules or protein phosphatase 1 catalytic subunits through overlapping binding sites, with higher PP1 affinity 4. Clinically, mutations in KNL1 cause autosomal recessive primary microcephaly (MCPH4), demonstrating its critical role in brain growth 5. Recent evidence indicates KNL1 regulates cytokinesis during cardiomyocyte proliferation through ATF4-mediated transcriptional control 6, highlighting its diverse cellular functions beyond mitotic checkpoint control.

Sources cited
1
KNL1 is a scaffolding protein required for kinetochore assembly, SAC function, and contains multiple protein interaction motifs (RVSF, SILK, MELT, KI) for recruiting checkpoint proteins
PMID: 25052095
2
KNL1 is an evolutionarily conserved kinetochore scaffold protein essential for chromosome segregation and involved in kinetochore assembly, chromosome congression, and mitotic checkpoint signaling
PMID: 24310619
3
The KNL1-Bub3-Bub1 pathway is required for SAC activation when kinetochores are misaligned but nonessential for SAC activation when kinetochores are unattached
PMID: 26651294
4
KNL1 can bind either to microtubules or to protein phosphatase 1 catalytic subunits (PPP1CA and PPP1CC) via overlapping binding sites, with higher affinity for PP1
PMID: 30100357
5
Mutations in KNL1/D40/CASC5 cause autosomal recessive primary microcephaly (MCPH4), providing evidence of the gene's critical role in brain growth
PMID: 28901661
6
ATF4 regulates KNL1 expression, leading to increased cytokinesis during cardiomyocyte proliferation and cardiac regeneration
PMID: 37905452
Disease Associationsβ“˜21
autosomal recessive primary microcephalyOpen Targets
0.75Strong
genetic disorderOpen Targets
0.41Moderate
Primary microcephalyOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
colon adenocarcinomaOpen Targets
0.37Weak
gastric carcinomaOpen Targets
0.37Weak
hemangioblastomaOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
prostate carcinomaOpen Targets
0.31Weak
hepatocellular carcinomaOpen Targets
0.30Weak
prostate adenocarcinomaOpen Targets
0.30Weak
breast carcinomaOpen Targets
0.29Weak
Microcephaly 4, primary, autosomal recessiveUniProt
Pathogenic Variants22
NM_144508.5(KNL1):c.3579del (p.Gly1194fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1194
NM_144508.5(KNL1):c.6172+2T>CLikely pathogenic
KNL1-related disorder|not provided
β˜…β˜†β˜†β˜†2024
NM_144508.5(KNL1):c.4537del (p.Thr1513fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 1513
NM_144508.5(KNL1):c.197_197+4delLikely pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2022
NM_144508.5(KNL1):c.1076del (p.Gly359fs)Pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2022β†’ Residue 359
NM_144508.5(KNL1):c.4693_4696del (p.Asn1565fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2022β†’ Residue 1565
NM_144508.5(KNL1):c.2044_2047del (p.Lys681_Gln682insTer)Likely pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2022β†’ Residue 681
NM_144508.5(KNL1):c.4076_4077del (p.Ser1359fs)Likely pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2021β†’ Residue 1359
NM_144508.5(KNL1):c.424_427del (p.Thr142fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 142
NM_144508.5(KNL1):c.6872C>T (p.Pro2291Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 2291
NM_144508.5(KNL1):c.1810C>T (p.Gln604Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 604
NM_144508.5(KNL1):c.5542_5543del (p.Gln1848fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 1848
NM_144508.5(KNL1):c.6125del (p.Asn2042fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 2042
NM_144508.5(KNL1):c.5542C>T (p.Gln1848Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 1848
NM_144508.5(KNL1):c.1521A>G (p.Gln507=)Likely pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2018β†’ Residue 507
NM_144508.5(KNL1):c.6349G>T (p.Asp2117Tyr)Likely pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2018β†’ Residue 2117
NM_144508.5(KNL1):c.5130dup (p.Ile1711fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 1711
NM_144508.5(KNL1):c.6304del (p.Asp2102fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 2102
NM_144508.5(KNL1):c.4745_4746delinsC (p.Leu1582fs)Likely pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2015β†’ Residue 1582
NM_144508.5(KNL1):c.5184dup (p.Ile1729fs)Pathogenic
Microcephaly 4, primary, autosomal recessive
β˜…β˜†β˜†β˜†2015β†’ Residue 1729
View on ClinVar β†—
Related Genes
CENPUProtein interaction100%CENPAProtein interaction100%CENPOProtein interaction100%CENPKProtein interaction100%CENPTProtein interaction100%CENPHProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
30%
Liver
9%
Lung
3%
Ovary
1%
Heart
1%
Gene Interaction Network
Click a node to explore
KNL1CENPUCENPACENPOCENPKCENPTCENPH
PROTEIN STRUCTURE
Preparing viewer…
PDB3SI5 Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.37Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.27 [0.21–0.37]
RankingsWhere KNL1 stands among ~20K protein-coding genes
  • #3,921of 20,598
    Most Researched120 Β· top quartile
  • #2,099of 5,498
    Most Pathogenic Variants22
  • #1,672of 17,882
    Most Constrained (LOEUF)0.37 Β· top 10%
Genes detectedKNL1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration.
PMID: 37905452
Circulation Β· 2023
1.00
2
KaryoCreate: A CRISPR-based technology to study chromosome-specific aneuploidy by targeting human centromeres.
PMID: 37075754
Cell Β· 2023
0.90
3
D40/KNL1/CASC5 and autosomal recessive primary microcephaly.
PMID: 28901661
Congenit Anom (Kyoto) Β· 2017
0.80
4
The dynamic protein Knl1 - a kinetochore rendezvous.
PMID: 25052095
J Cell Sci Β· 2014
0.70
5
KNL1: bringing order to the kinetochore.
PMID: 24310619
Chromosoma Β· 2014
0.60