The protein encoded by this gene is a component of the multiprotein assembly that is required for creation of kinetochore-microtubule attachments and chromosome segregation. The encoded protein functions as a scaffold for proteins that influence the spindle assembly checkpoint during the eukaryotic cell cycle and it interacts with at least five different kinetochore proteins an... See more...

Aliases for KNL1 Gene

Aliases for KNL1 Gene

  • Kinetochore Scaffold 1 2 3 4 5
  • Cancer/Testis Antigen 29 2 3 4
  • CT29 2 3 4
  • Cancer Susceptibility Candidate Gene 5 Protein 3 4
  • ALL1-Fused Gene From Chromosome 15q14 Protein 3 4
  • Protein Phosphatase 1, Regulatory Subunit 55 2 3
  • Microcephaly, Primary Autosomal Recessive 4 2 3
  • Blinkin, Bub-Linking Kinetochore Protein 2 3
  • Cancer Susceptibility Candidate 5 2 3
  • Kinetochore-Null Protein 1 3 4
  • KIAA1570 2 4
  • AF15Q14 2 3
  • PPP1R55 2 3
  • HSpc105 2 3
  • HKNL-1 2 3
  • CASC5 3 4
  • Spc7 2 3
  • D40 2 3
  • Kinetochore Null 1 Homolog (C. Elegans) 2
  • Bub-Linking Kinetochore Protein 4
  • Kinetochore Null 1 Homolog 3
  • Protein D40/AF15q14 4
  • Protein CASC5 4
  • AF15q14 4
  • Blinkin 4
  • MCPH4 3
  • KNL1 5

External Ids for KNL1 Gene

Previous HGNC Symbols for KNL1 Gene

  • MCPH4
  • CASC5

Summaries for KNL1 Gene

Entrez Gene Summary for KNL1 Gene

  • The protein encoded by this gene is a component of the multiprotein assembly that is required for creation of kinetochore-microtubule attachments and chromosome segregation. The encoded protein functions as a scaffold for proteins that influence the spindle assembly checkpoint during the eukaryotic cell cycle and it interacts with at least five different kinetochore proteins and two checkpoint kinases. In adults, this gene is predominantly expressed in normal testes, various cancer cell lines and primary tumors from other tissues and is ubiquitously expressed in fetal tissues. This gene was originally identified as a fusion partner with the mixed-lineage leukemia (MLL) gene in t(11;15)(q23;q14). Mutations in this gene cause autosomal recessive primary microcephaly-4 (MCPH4). Alternative splicing results in multiple transcript variants encoding different isoforms. Additional splice variants have been described but their biological validity has not been confirmed. [provided by RefSeq, Jan 2013]

GeneCards Summary for KNL1 Gene

KNL1 (Kinetochore Scaffold 1) is a Protein Coding gene. Diseases associated with KNL1 include Microcephaly 4, Primary, Autosomal Recessive and Primary Autosomal Recessive Microcephaly. Among its related pathways are Signaling by GPCR and Mitotic Prometaphase.

UniProtKB/Swiss-Prot Summary for KNL1 Gene

  • Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.

Gene Wiki entry for KNL1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KNL1 Gene

Genomics for KNL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KNL1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KNL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KNL1

Genomic Locations for KNL1 Gene

Genomic Locations for KNL1 Gene
chr15:40,594,012-40,664,342
(GRCh38/hg38)
Size:
70,331 bases
Orientation:
Plus strand
chr15:40,886,218-40,956,540
(GRCh37/hg19)
Size:
70,323 bases
Orientation:
Plus strand

Genomic View for KNL1 Gene

Genes around KNL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KNL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KNL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KNL1 Gene

Proteins for KNL1 Gene

  • Protein details for KNL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NG31-KNL1_HUMAN
    Recommended name:
    Kinetochore scaffold 1
    Protein Accession:
    Q8NG31
    Secondary Accessions:
    • Q8NHE1
    • Q8WXA6
    • Q9HCK2
    • Q9NR92

    Protein attributes for KNL1 Gene

    Size:
    2342 amino acids
    Molecular mass:
    265391 Da
    Quaternary structure:
    • Interacts with DSN1, MIS12, BUB1, BUB1B, NSL1 and ZWINT.

    Three dimensional structures from OCA and Proteopedia for KNL1 Gene

    Alternative splice isoforms for KNL1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KNL1 Gene

Post-translational modifications for KNL1 Gene

  • Ubiquitination at Lys202, Lys213, Lys246, Lys303, Lys467, Lys501, Lys643, Lys666, Lys680, Lys707, Lys726, Lys757, Lys777, Lys810, Lys846, Lys1072, Lys1165, Lys1214, Lys1229, Lys1240, Lys1285, Lys1295, Lys1481, and Lys1584
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for KNL1 Gene

Domains & Families for KNL1 Gene

Gene Families for KNL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for KNL1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for KNL1 Gene

GenScript: Design optimal peptide antigens:
  • Protein D40/AF15q14 (CASC5_HUMAN)
  • CASC5 protein (Q05C46_HUMAN)
genes like me logo Genes that share domains with KNL1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for KNL1 Gene

Function for KNL1 Gene

Molecular function for KNL1 Gene

UniProtKB/Swiss-Prot Function:
Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.

Phenotypes From GWAS Catalog for KNL1 Gene

Gene Ontology (GO) - Molecular Function for KNL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15231748
genes like me logo Genes that share ontologies with KNL1: view
genes like me logo Genes that share phenotypes with KNL1: view

Human Phenotype Ontology for KNL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KNL1 Gene

MGI Knock Outs for KNL1:
  • Knl1 Knl1<tm1b(EUCOMM)Hmgu>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KNL1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for KNL1 Gene

Localization for KNL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KNL1 Gene

Nucleus. Chromosome, centromere, kinetochore. Note=Weakly expressed in interphase nuclei. Expression increases from prophase to late anaphase, but greatly diminishes from the telophase and cytokinesis to early G1 phase of cell cycle.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KNL1 gene
Compartment Confidence
nucleus 5
cytosol 5
cytoskeleton 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (4)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KNL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000775 chromosome, centromeric region IEA --
GO:0000776 kinetochore IEA --
GO:0000777 condensed chromosome kinetochore IDA 15371340
GO:0001669 acrosomal vesicle IDA 15579588
GO:0005634 nucleus IEA,IDA 10980622
genes like me logo Genes that share ontologies with KNL1: view

Pathways & Interactions for KNL1 Gene

genes like me logo Genes that share pathways with KNL1: view

SIGNOR curated interactions for KNL1 Gene

Activates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for KNL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001675 acrosome assembly NAS 15579588
GO:0007049 cell cycle IEA --
GO:0007059 chromosome segregation IEA --
GO:0008608 attachment of spindle microtubules to kinetochore IEA,IDA 17981135
GO:0010923 negative regulation of phosphatase activity IDA 19389623
genes like me logo Genes that share ontologies with KNL1: view

Drugs & Compounds for KNL1 Gene

No Compound Related Data Available

Transcripts for KNL1 Gene

mRNA/cDNA for KNL1 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KNL1

Alternative Splicing Database (ASD) splice patterns (SP) for KNL1 Gene

No ASD Table

Relevant External Links for KNL1 Gene

GeneLoc Exon Structure for
KNL1

Expression for KNL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KNL1

mRNA Expression by UniProt/SwissProt for KNL1 Gene:

Q8NG31-KNL1_HUMAN
Tissue specificity: Highly expressed in testis, where it is localized in germ cells, in particular in spermatocytes and in the pre-acrosome of round spermatids. Detected in the acrosome of ejaculated spermatozoa. Detected in adult thymus, bone marrow, colon, small intestine, appendix and placenta, and in fetal liver and thymus.

Evidence on tissue expression from TISSUES for KNL1 Gene

  • Nervous system(4.4)
  • Pancreas(3.3)
  • Skin(2.6)
  • Blood(2.3)
  • Intestine(2.1)
  • Kidney(2)
  • Liver(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for KNL1 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • chin
  • cranial nerve
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
Pelvis:
  • pelvis
  • ureter
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with KNL1: view

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for KNL1 Gene

Orthologs for KNL1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KNL1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CASC5 30 31
  • 98.78 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CASC5 30 31
  • 84.56 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CASC5 30
  • 84.28 (n)
Rat
(Rattus norvegicus)
Mammalia Casc5 30
  • 77.89 (n)
Mouse
(Mus musculus)
Mammalia Casc5 30 31
  • 77.63 (n)
OneToOne
Knl1 17
Platypus
(Ornithorhynchus anatinus)
Mammalia CASC5 31
  • 56 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CASC5 31
  • 45 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CASC5 30 31
  • 55 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CASC5 31
  • 64 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii casc5 31
  • 18 (a)
OneToOne
Species where no ortholog for KNL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for KNL1 Gene

ENSEMBL:
Gene Tree for KNL1 (if available)
TreeFam:
Gene Tree for KNL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KNL1: view image

Paralogs for KNL1 Gene

No data available for Paralogs for KNL1 Gene

Variants for KNL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KNL1 Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
39707 Pathogenic: Primary autosomal recessive microcephaly 4 40,647,025(+) G/A MISSENSE_VARIANT
716182 Benign: not provided 40,620,715(+) A/G MISSENSE_VARIANT
718880 Likely Benign: not provided 40,650,569(+) A/G SYNONYMOUS_VARIANT
719991 Likely Benign: not provided 40,641,034(+) A/G INTRON_VARIANT
721506 Likely Benign: not provided 40,662,071(+) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for KNL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for KNL1 Gene

Variant ID Type Subtype PubMed ID
esv2135247 CNV deletion 18987734
esv2749603 CNV deletion 23290073
esv2760026 CNV loss 17122850
esv34145 CNV loss 18971310
esv992789 CNV deletion 20482838
nsv1138356 CNV deletion 24896259
nsv7263 OTHER inversion 18451855
nsv832984 CNV loss 17160897
nsv958034 CNV deletion 24416366

Variation tolerance for KNL1 Gene

Residual Variation Intolerance Score: 97.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.90; 91.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KNL1 Gene

Human Gene Mutation Database (HGMD)
KNL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KNL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KNL1 Gene

Disorders for KNL1 Gene

MalaCards: The human disease database

(16) MalaCards diseases for KNL1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search KNL1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

KNL1_HUMAN
  • Note=A chromosomal aberration involving KNL1 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A. May give rise to a KMT2A-KNL1 fusion protein. {ECO:0000269 PubMed:12618766}.
  • Microcephaly 4, primary, autosomal recessive (MCPH4) [MIM:604321]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. {ECO:0000269 PubMed:22983954, ECO:0000269 PubMed:26626498}. Note=The disease is caused by mutations affecting the gene represented in this entry.
genes like me logo Genes that share disorders with KNL1: view

No data available for Genatlas for KNL1 Gene

Publications for KNL1 Gene

  1. AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14). (PMID: 10980622) Hayette S … Rimokh R (Oncogene 2000) 2 3 4 23
  2. KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates. (PMID: 18045986) Cheeseman IM … Desai A (Molecular biology of the cell 2008) 2 3 4
  3. The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa. (PMID: 15579588) Sasao T … Takimoto M (Reproduction (Cambridge, England) 2004) 3 4 23
  4. Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14). (PMID: 12618768) Kuefer MU … Morris SW (Oncogene 2003) 3 4 23
  5. A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15. (PMID: 12618766) Chinwalla V … Rowley JD (Oncogene 2003) 3 4 23

Products for KNL1 Gene

Sources for KNL1 Gene