KNL1 kinetochore scaffold 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KNL1provided by HGNC
Official Full Name: kinetochore scaffold 1provided by HGNC
Primary source: HGNC:HGNC:24054
See related: Ensembl:ENSG00000137812 MIM:609173; AllianceGenome:HGNC:24054
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: D40; CT29; Spc7; CASC5; MCPH4; hKNL-1; AF15Q14; PPP1R55; hSpc105
Summary: 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]
Expression: Biased expression in testis (RPKM 14.1), bone marrow (RPKM 2.9) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q15.1

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (40594249..40664342)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (38399974..38470044)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (40886447..40956540)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Kinetochore scaffold 1 downregulation suppressed the development of non-small cell lung cancer by inactivating the phosphatidylinositol 3 kinase/protein kinase B (AKT)/nuclear factor-kappa B pathway.
Title: Kinetochore scaffold 1 downregulation suppressed the development of non-small cell lung cancer by inactivating the phosphatidylinositol 3 kinase/protein kinase B (AKT)/nuclear factor-kappa B pathway.
A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.
Title: A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.
LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression.
Title: LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression.
CASC5 is a potential tumour driving gene in lung adenocarcinoma.
Title: CASC5 is a potential tumour driving gene in lung adenocarcinoma.
[CASC5</I> Gene Expression Changes Correlate with Targeted Mutations in Leukemia].
Title: [CASC5</I> Gene Expression Changes Correlate with Targeted Mutations in Leukemia].
KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.
Title: Effect of KNL1 on the proliferation and apoptosis of colorectal cancer cells.
KNL1 mutation is associated with Microcephaly.
Title: Microcephaly Modeling of Kinetochore Mutation Reveals a Brain-Specific Phenotype.
Data show how KNL1 binds both PP1 and microtubules. Unexpectedly, PP1 and microtubules bind KNL1 via overlapping binding sites. Co-sedimentation assays unequivocally demonstrated that microtubules and PP1 binding to KNL1 is mutually exclusive, with preferential formation of the KNL1:PP1 holoenzyme in the presence of PP1.
Title: KNL1 Binding to PP1 and Microtubules Is Mutually Exclusive.
Study demonstrates that KNL1 acts as a receptor of linear ubiquitin chains to anchor CENP-E at attached kinetochores. Thus, linear ubiquitin chains constitute a critical mechanism for chromosome congression and alignment by coupling the dynamic kinetochore microtubule motor CENP-E to the static one, the KMN network.
Title: LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores.
Mutations in the CASC5 gene were found to encode a kinetochore protein essential for mitotic cell division and to cause autosomal recessive primary microcephaly 4. (Review)
Title: D40/KNL1/CASC5 and autosomal recessive primary microcephaly.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Microcephaly 4, primary, autosomal recessive MedGen: C1858516 OMIM: 604321 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-T81591 (e-PCR)
- UniSTS:6928

RH93617 (e-PCR)
- UniSTS:91523

RH122445 (e-PCR)
- UniSTS:135316

RH120094 (e-PCR)
- UniSTS:132299

SGC44363 (e-PCR)
- UniSTS:80344

SHGC-44363 (e-PCR)
- UniSTS:48356

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in acrosome assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in attachment of spindle microtubules to kinetochore	IBA Inferred from Biological aspect of Ancestor more info
involved_in attachment of spindle microtubules to kinetochore	IDA Inferred from Direct Assay more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in homologous chromosome orientation in meiotic metaphase I	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitotic sister chromatid segregation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of meiosis I spindle assembly checkpoint	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to kinetochore	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within protein localization to kinetochore	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of mitotic cell cycle spindle assembly checkpoint	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of Knl1/Spc105 complex	IDA Inferred from Direct Assay more info	PubMed
located_in acrosomal vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in kinetochore	IDA Inferred from Direct Assay more info	PubMed
located_in kinetochore	NAS Non-traceable Author Statement more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: kinetochore scaffold 1

Names: ALL1-fused gene from chromosome 15q14 protein; blinkin, bub-linking kinetochore protein; cancer susceptibility candidate 5; cancer susceptibility candidate gene 5 protein; cancer/testis antigen 29; kinetochore null 1 homolog; kinetochore-null protein 1; microcephaly, primary autosomal recessive 4; protein phosphatase 1, regulatory subunit 55

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033114.1 RefSeqGene

Range

5001..75094

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_144508.5 → NP_653091.3 kinetochore scaffold 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AB046790, AC022405, AF461041, BC014306

Consensus CDS

CCDS42024.1

UniProtKB/Swiss-Prot

Q8NG31

Related

ENSP00000382576.3, ENST00000399668.7

Conserved Domains (5) summary

COG1196
Location:1916 → 2104

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

pfam19221
Location:857 → 882

MELT; MELT motif

cd22817
Location:2095 → 2205

Knl1_RWD_N; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) N-terminal domain

cd22892
Location:2212 → 2310

Knl1_RWD_C; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) C-terminal domain

cd21853
Location:20 → 75

KNL1_NTD; N-terminal domain found in kinetochore scaffold 1 (KNL1) and similar proteins
NM_170589.5 → NP_733468.3 kinetochore scaffold 1 isoform 1

See identical proteins and their annotated locations for NP_733468.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AB046790, AC022405, AF173994, AF461041, BC014306

Consensus CDS

CCDS42023.1

UniProtKB/Swiss-Prot

Q8NG31, Q8NHE1, Q8WXA6, Q9HCK2, Q9NR92

Related

ENSP00000335463.6, ENST00000346991.9

Conserved Domains (5) summary

COG1196
Location:1942 → 2130

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

pfam19221
Location:883 → 908

MELT; MELT motif

cd22817
Location:2121 → 2231

Knl1_RWD_N; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) N-terminal domain

cd22892
Location:2238 → 2336

Knl1_RWD_C; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) C-terminal domain

cd21853
Location:20 → 75

KNL1_NTD; N-terminal domain found in kinetochore scaffold 1 (KNL1) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

40594249..40664342

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

38399974..38470044

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054378486.1 → XP_054234461.1 kinetochore scaffold 1 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_020380.2: Suppressed sequence

Description

NM_020380.2: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.