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    NEK6 NIMA related kinase 6 [ Homo sapiens (human) ]

    Gene ID: 10783, updated on 27-Nov-2024

    Summary

    Official Symbol
    NEK6provided by HGNC
    Official Full Name
    NIMA related kinase 6provided by HGNC
    Primary source
    HGNC:HGNC:7749
    See related
    Ensembl:ENSG00000119408 MIM:604884; AllianceGenome:HGNC:7749
    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
    SID6-1512
    Summary
    The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
    Expression
    Ubiquitous expression in placenta (RPKM 13.1), appendix (RPKM 13.0) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NEK6 in Genome Data Viewer
    Location:
    9q33.3
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (124257606..124353307)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (136455708..136551354)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (127019885..127115586)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:126774959-126775531 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:126775532-126776104 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:126792309-126793096 Neighboring gene uncharacterized LOC107987037 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:126803186-126803720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:126803721-126804253 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:126807814-126808609 Neighboring gene LIM homeobox 2 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:126840763-126841962 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28957 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:126893859-126894071 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28958 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28959 Neighboring gene Sharpr-MPRA regulatory region 10969 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:126905749-126906322 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:126906323-126906898 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:126906899-126907472 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28960 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28962 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:126964420-126964620 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28964 Neighboring gene NFE2L2 motif-containing MPRA enhancer 159 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20258 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20259 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28967 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28966 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28969 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28970 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127004798-127005314 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127005315-127005831 Neighboring gene Sharpr-MPRA regulatory region 14990 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28971 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28973 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28972 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20260 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20261 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:127020845-127021790 Neighboring gene uncharacterized LOC124902268 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127026232-127026845 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20262 Neighboring gene uncharacterized LOC613206 Neighboring gene Sharpr-MPRA regulatory region 10556 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:127047786-127047960 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr9:127048049-127049248 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28977 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28978 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28979 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127054700-127055684 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28980 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28981 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:127058683-127059590 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:127061405-127062310 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:127070759-127071606 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:127071689-127072888 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127077520-127078020 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28982 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28983 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28984 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127104704-127105575 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127105576-127106448 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_106555 Neighboring gene uncharacterized LOC100129034 Neighboring gene uncharacterized LOC124902267 Neighboring gene proteasome 20S subunit beta 7

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables AMP-activated protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables DNA-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables Rho-dependent protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables eukaryotic translation initiation factor 2alpha kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AS121 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AT120 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AXS139 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2BS14 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2BS36 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3S10 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3S28 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3S57 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T11 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T3 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T45 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H4S1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables kinesin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
     
    enables ribosomal protein S6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables transcription corepressor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in centriolar satellite IDA
    Inferred from Direct Assay
    more info
     
    colocalizes_with centrosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in microtubule IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nuclear speck IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in spindle pole IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    serine/threonine-protein kinase Nek6
    Names
    NIMA (never in mitosis gene a)-related kinase 6
    never in mitosis A-related kinase 6
    nimA-related protein kinase 6
    protein kinase SID6-1512
    putative serine-threonine protein kinase
    NP_001138473.1
    NP_001159639.1
    NP_001159640.1
    NP_001159641.1
    NP_001159642.1
    NP_001159643.1
    NP_055212.2
    XP_016869706.1
    XP_024303155.1
    XP_047278607.1
    XP_047278608.1
    XP_047278609.1
    XP_047278610.1
    XP_054217767.1
    XP_054217768.1
    XP_054217769.1
    XP_054217770.1
    XP_054217771.1
    XP_054217772.1
    XP_054217773.1
    XP_054217774.1
    XP_054217775.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001145001.3NP_001138473.1  serine/threonine-protein kinase Nek6 isoform 1

      See identical proteins and their annotated locations for NP_001138473.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Variants 1 and 7 encode the same isoform (1).
      Source sequence(s)
      AF087909, AL137846, BC004174, BC012761, CF994196
      Consensus CDS
      CCDS48015.1
      UniProtKB/Swiss-Prot
      Q9HC98
      Related
      ENSP00000362702.3, ENST00000373600.7
      Conserved Domains (2) summary
      smart00220
      Location:79344
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08228
      Location:76343
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    2. NM_001166167.2NP_001159639.1  serine/threonine-protein kinase Nek6 isoform 3

      See identical proteins and their annotated locations for NP_001159639.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AF087909, AL137846, BC012761, BM083872
      Consensus CDS
      CCDS55338.1
      UniProtKB/Swiss-Prot
      Q9HC98
      Related
      ENSP00000441469.1, ENST00000540326.5
      Conserved Domains (2) summary
      smart00220
      Location:63328
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08228
      Location:60327
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    3. NM_001166168.2NP_001159640.1  serine/threonine-protein kinase Nek6 isoform 2

      See identical proteins and their annotated locations for NP_001159640.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Variants 2, 5 and 6 encode the same isoform (2).
      Source sequence(s)
      AF087909, AL137846, AL162724, BC012761, BP279761
      Consensus CDS
      CCDS6854.1
      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
      Related
      ENSP00000442636.1, ENST00000545174.5
      Conserved Domains (1) summary
      cd08228
      Location:42309
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    4. NM_001166169.2NP_001159641.1  serine/threonine-protein kinase Nek6 isoform 4

      See identical proteins and their annotated locations for NP_001159641.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (4) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AK294614, AL137846, AL162724, BC012761
      Consensus CDS
      CCDS55339.1
      UniProtKB/Swiss-Prot
      Q9HC98
      Related
      ENSP00000439651.1, ENST00000539416.5
      Conserved Domains (2) summary
      smart00220
      Location:70335
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08228
      Location:67334
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    5. NM_001166170.2NP_001159642.1  serine/threonine-protein kinase Nek6 isoform 2

      See identical proteins and their annotated locations for NP_001159642.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Variants 2, 5 and 6 encode the same isoform (2).
      Source sequence(s)
      AL137846, AL162724, BC012761
      Consensus CDS
      CCDS6854.1
      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
      Related
      ENSP00000441426.1, ENST00000546191.5
      Conserved Domains (1) summary
      cd08228
      Location:42309
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    6. NM_001166171.2NP_001159643.1  serine/threonine-protein kinase Nek6 isoform 1

      See identical proteins and their annotated locations for NP_001159643.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 1. Both variants 1 and 7 encode the same protein.
      Source sequence(s)
      AL137846, AL162724, BC012761, DB350175
      Consensus CDS
      CCDS48015.1
      UniProtKB/Swiss-Prot
      Q9HC98
      Related
      ENSP00000377749.2, ENST00000394199.6
      Conserved Domains (2) summary
      smart00220
      Location:79344
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08228
      Location:76343
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    7. NM_014397.6NP_055212.2  serine/threonine-protein kinase Nek6 isoform 2

      See identical proteins and their annotated locations for NP_055212.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Variants 2, 5 and 6 encode the same isoform (2).
      Source sequence(s)
      AF087909, AL137846, BC012761, CF994196
      Consensus CDS
      CCDS6854.1
      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
      Related
      ENSP00000319734.5, ENST00000320246.10
      Conserved Domains (1) summary
      cd08228
      Location:42309
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      124257606..124353307
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047422652.1XP_047278608.1  serine/threonine-protein kinase Nek6 isoform X2

    2. XM_024447387.2XP_024303155.1  serine/threonine-protein kinase Nek6 isoform X4

      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
      Conserved Domains (1) summary
      cd08228
      Location:42309
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    3. XM_047422653.1XP_047278609.1  serine/threonine-protein kinase Nek6 isoform X3

    4. XM_017014217.2XP_016869706.1  serine/threonine-protein kinase Nek6 isoform X2

      UniProtKB/Swiss-Prot
      Q9HC98
      Conserved Domains (2) summary
      smart00220
      Location:79344
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08228
      Location:76343
      STKc_Nek6; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6
    5. XM_047422651.1XP_047278607.1  serine/threonine-protein kinase Nek6 isoform X1

    6. XM_047422654.1XP_047278610.1  serine/threonine-protein kinase Nek6 isoform X2

    RNA

    1. XR_007061235.1 RNA Sequence

    2. XR_007061234.1 RNA Sequence

    3. XR_007061237.1 RNA Sequence

    4. XR_007061236.1 RNA Sequence

    5. XR_007061238.1 RNA Sequence

    6. XR_007061233.1 RNA Sequence

    7. XR_007061232.1 RNA Sequence

    8. XR_007061231.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      136455708..136551354
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054361796.1XP_054217771.1  serine/threonine-protein kinase Nek6 isoform X4

      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
    2. XM_054361797.1XP_054217772.1  serine/threonine-protein kinase Nek6 isoform X4

      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
    3. XM_054361798.1XP_054217773.1  serine/threonine-protein kinase Nek6 isoform X4

      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
    4. XM_054361794.1XP_054217769.1  serine/threonine-protein kinase Nek6 isoform X3

    5. XM_054361800.1XP_054217775.1  serine/threonine-protein kinase Nek6 isoform X4

      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
    6. XM_054361793.1XP_054217768.1  serine/threonine-protein kinase Nek6 isoform X2

    7. XM_054361792.1XP_054217767.1  serine/threonine-protein kinase Nek6 isoform X1

    8. XM_054361799.1XP_054217774.1  serine/threonine-protein kinase Nek6 isoform X4

      UniProtKB/Swiss-Prot
      B7Z2D9, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9HC98, Q9ULX2
    9. XM_054361795.1XP_054217770.1  serine/threonine-protein kinase Nek6 isoform X2