Seroatlas · Human Serome Atlas

KNL1

Outer kinetochore KNL1 complex subunit KNL1

Also known as: AF15Q14, CASC5, CT29, D40, hKNL-1, hSpc105, KIAA1570, KNL1_HUMAN, MCPH4, PPP1R55, Spc7

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q8NG31
Gene: KNL1
Ensembl: ENSG00000137812
Chromosome: 15
Canonical length: 2342 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Nuclear bodies

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

2342 residues, UniProt reviewed canonical sequence.

>Q8NG31|KNL1
     1  MDGVSSEANE ENDNIERPVR RRHSSILKPP RSPLQDLRGG NERVQESNAL RNKKNSRRVS
    61  FADTIKVFQT ESHMKIVRKS EMEGCSAMVP SQLQLLPPGF KRFSCLSLPE TETGENLLLI
   121  QNKKLEDNYC EITGMNTLLS APIHTQMQQK EFSIIEHTRE RKHANDQTVI FSDENQMDLT
   181  SSHTVMITKG LLDNPISEKS TKIDTTSFLA NLKLHTEDSR MKKEVNFSVD QNTSSENKID
   241  FNDFIKRLKT GKCSAFPDVP DKENFEIPIY SKEPNSASST HQMHVSLKED ENNSNITRLF
   301  REKDDGMNFT QCHTANIQTL IPTSSETNSR ESKGNDITIY GNDFMDLTFN HTLQILPATG
   361  NFSEIENQTQ NAMDVTTGYG TKASGNKTVF KSKQNTAFQD LSINSADKIH ITRSHIMGAE
   421  THIVSQTCNQ DARILAMTPE SIYSNPSIQG CKTVFYSSCN DAMEMTKCLS NMREEKNLLK
   481  HDSNYAKMYC NPDAMSSLTE KTIYSGEENM DITKSHTVAI DNQIFKQDQS NVQIAAAPTP
   541  EKEMMLQNLM TTSEDGKMNV NCNSVPHVSK ERIQQSLSNP LSISLTDRKT ELLSGENMDL
   601  TESHTSNLGS QVPLAAYNLA PESTSESHSQ SKSSSDECEE ITKSRNEPFQ RSDIIAKNSL
   661  TDTWNKDKDW VLKILPYLDK DSPQSADCNQ EIATSHNIVY CGGVLDKQIT NRNTVSWEQS
   721  LFSTTKPLFS SGQFSMKNHD TAISSHTVKS VLGQNSKLAE PLRKSLSNPT PDYCHDKMII
   781  CSEEEQNMDL TKSHTVVIGF GPSELQELGK TNLEHTTGQL TTMNRQIAVK VEKCGKSPIE
   841  KSGVLKSNCI MDVLEDESVQ KPKFPKEKQN VKIWGRKSVG GPKIDKTIVF SEDDKNDMDI
   901  TKSYTIEINH RPLLEKRDCH LVPLAGTSET ILYTCRQDDM EITRSHTTAL ECKTVSPDEI
   961  TTRPMDKTVV FVDNHVELEM TESHTVFIDY QEKERTDRPN FELSQRKSLG TPTVICTPTE
  1021  ESVFFPGNGE SDRLVANDSQ LTPLEEWSNN RGPVEVADNM ELSKSATCKN IKDVQSPGFL
  1081  NEPLSSKSQR RKSLKLKNDK TIVFSENHKN DMDITQSCMV EIDNESALED KEDFHLAGAS
  1141  KTILYSCGQD DMEITRSHTT ALECKTLLPN EIAIRPMDKT VLFTDNYSDL EVTDSHTVFI
  1201  DCQATEKILE ENPKFGIGKG KNLGVSFPKD NSCVQEIAEK QALAVGNKIV LHTEQKQQLF
  1261  AATNRTTNEI IKFHSAAMDE KVIGKVVDQA CTLEKAQVES CQLNNRDRRN VDFTSSHATA
  1321  VCGSSDNYSC LPNVISCTDN LEGSAMLLCD KDEEKANYCP VQNDLAYAND FASEYYLESE
  1381  GQPLSAPCPL LEKEEVIQTS TKGQLDCVIT LHKDQDLIKD PRNLLANQTL VYSQDLGEMT
  1441  KLNSKRVSFK LPKDQMKVYV DDIYVIPQPH FSTDQPPLPK KGQSSINKEE VILSKAGNKS
  1501  LNIIENSSAP ICENKPKILN SEEWFAAACK KELKENIQTT NYNTALDFHS NSDVTKQVIQ
  1561  THVNAGEAPD PVITSNVPCF HSIKPNLNNL NGKTGEFLAF QTVHLPPLPE QLLELGNKAH
  1621  NDMHIVQATE IHNINIISSN AKDSRDEENK KSHNGAETTS LPPKTVFKDK VRRCSLGIFL
  1681  PRLPNKRNCS VTGIDDLEQI PADTTDINHL ETQPVSSKDS GIGSVAGKLN LSPSQYINEE
  1741  NLPVYPDEIN SSDSINIETE EKALIETYQK EISPYENKMG KTCNSQKRTW VQEEEDIHKE
  1801  KKIRKNEIKF SDTTQDREIF DHHTEEDIDK SANSVLIKNL SRTPSSCSSS LDSIKADGTS
  1861  LDFSTYRSSQ MESQFLRDTI CEESLREKLQ DGRITIREFF ILLQVHILIQ KPRQSNLPGN
  1921  FTVNTPPTPE DLMLSQYVYR PKIQIYREDC EARRQKIEEL KLSASNQDKL LVDINKNLWE
  1981  KMRHCSDKEL KAFGIYLNKI KSCFTKMTKV FTHQGKVALY GKLVQSAQNE REKLQIKIDE
  2041  MDKILKKIDN CLTEMETETK NLEDEEKNNP VEEWDSEMRA AEKELEQLKT EEEELQRNLL
  2101  ELEVQKEQTL AQIDFMQKQR NRTEELLDQL SLSEWDVVEW SDDQAVFTFV YDTIQLTITF
  2161  EESVVGFPFL DKRYRKIVDV NFQSLLDEDQ APPSSLLVHK LIFQYVEEKE SWKKTCTTQH
  2221  QLPKMLEEFS LVVHHCRLLG EEIEYLKRWG PNYNLMNIDI NNNELRLLFS SSAAFAKFEI
  2281  TLFLSAYYPS VPLPSTIQNH VGNTSQDDIA TILSKVPLEN NYLKNVVKQI YQDLFQDCHF
  2341  YH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KNL1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.61
Highest tissue expression: 16 nTPM

Expression across tissuesHPA

Tissue

testis: 16 nTPM
thymus: 6.9 nTPM
bone marrow: 4.9 nTPM
lymph node: 3.4 nTPM
tonsil: 3.2 nTPM
appendix: 1.7 nTPM

Single-cell type

early primary spermatocytes: 498 nCPM
monocyte progenitors: 211 nCPM
differentiating spermatogonia: 203 nCPM
erythrocyte progenitors: 142 nCPM
neutrophil progenitors: 125 nCPM
megakaryocyte progenitors: 120 nCPM

Immune cell

memory B-cell: 0.7 nTPM
naive B-cell: 0.5 nTPM
T-reg: 0.4 nTPM
myeloid DC: 0.3 nTPM
memory CD4 T-cell: 0.2 nTPM
basophil: 0.1 nTPM

Brain region

cerebral cortex: 1.5 nTPM
pons: 1.4 nTPM
thalamus: 1.3 nTPM
choroid plexus: 1.2 nTPM
cerebellum: 1 nTPM
white matter: 1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KNL1.

Disease | AllUniProt

Conditions KNL1 is implicated in, by any mechanism.

Microcephaly 4, primary, autosomal recessive (MCPH4) MIM:604321

Disease | GeneticClinVar

22 pathogenic / likely-pathogenic of 431 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Microcephaly 4, primary, autosomal recessive
Inborn genetic diseases
KNL1-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.31
gnomAD pLI: 0.78
DepMap mean gene effect: -0.9
DepMap dependency class: common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

acrosome assembly
attachment of spindle microtubules to kinetochore
cell division
homologous chromosome orientation in meiotic metaphase I
mitotic sister chromatid segregation
protein localization to kinetochore
regulation of mitotic cell cycle spindle assembly checkpoint
positive regulation of meiosis I spindle assembly checkpoint

Molecular functions

microtubule binding

Cellular components

Protein domainsUniProt · Pfam · InterPro

Kinetochore scaffold 1
Knl1, C-terminal RWD domain
KNL1 MELT repeat
Knl1 RWD C-terminal domain
MELT motif

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of KNL1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads KNL1 as an antibody target. Whether an autoantibody or antibody against KNL1 could matter depends on whether native KNL1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

KNL1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label KNL1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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