KIDINS220

Protein identityUniProt · HPA

UniProt accession

Q9ULH0

Gene

KIDINS220

Ensembl

ENSG00000134313

Chromosome

2

Canonical length

1771 aa

Protein class

Disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Vesicles,Cytosol

OverviewNCBI Gene

This gene encodes a transmembrane protein that is preferentially expressed in the nervous system where it controls neuronal cell survival, differentiation into exons and dendrites, and synaptic plasticity. The encoded protein interacts with membrane receptors, cytosolic signaling components, and cytoskeletal proteins, serving as a scaffold that mediates crosstalk between the neurotrophin pathway and several other intracellular signaling pathways. Aberrant expression of this gene is associated with the onset of various neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease. Naturally occurring mutations in this gene are associated with a syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

Canonical amino-acid sequenceUniProt

1771 residues, UniProt reviewed canonical sequence.

>Q9ULH0|KIDINS220
     1  MSVLISQSVI NYVEEENIPA LKALLEKCKD VDERNECGQT PLMIAAEQGN LEIVKELIKN
    61  GANCNLEDLD NWTALISASK EGHVHIVEEL LKCGVNLEHR DMGGWTALMW ACYKGRTDVV
   121  ELLLSHGANP SVTGLYSVYP IIWAAGRGHA DIVHLLLQNG AKVNCSDKYG TTPLVWAARK
   181  GHLECVKHLL AMGADVDQEG ANSMTALIVA VKGGYTQSVK EILKRNPNVN LTDKDGNTAL
   241  MIASKEGHTE IVQDLLDAGT YVNIPDRSGD TVLIGAVRGG HVEIVRALLQ KYADIDIRGQ
   301  DNKTALYWAV EKGNATMVRD ILQCNPDTEI CTKDGETPLI KATKMRNIEV VELLLDKGAK
   361  VSAVDKKGDT PLHIAIRGRS RKLAELLLRN PKDGRLLYRP NKAGETPYNI DCSHQKSILT
   421  QIFGARHLSP TETDGDMLGY DLYSSALADI LSEPTMQPPI CVGLYAQWGS GKSFLLKKLE
   481  DEMKTFAGQQ IEPLFQFSWL IVFLTLLLCG GLGLLFAFTV HPNLGIAVSL SFLALLYIFF
   541  IVIYFGGRRE GESWNWAWVL STRLARHIGY LELLLKLMFV NPPELPEQTT KALPVRFLFT
   601  DYNRLSSVGG ETSLAEMIAT LSDACEREFG FLATRLFRVF KTEDTQGKKK WKKTCCLPSF
   661  VIFLFIIGCI ISGITLLAIF RVDPKHLTVN AVLISIASVV GLAFVLNCRT WWQVLDSLLN
   721  SQRKRLHNAA SKLHKLKSEG FMKVLKCEVE LMARMAKTID SFTQNQTRLV VIIDGLDACE
   781  QDKVLQMLDT VRVLFSKGPF IAIFASDPHI IIKAINQNLN SVLRDSNING HDYMRNIVHL
   841  PVFLNSRGLS NARKFLVTSA TNGDVPCSDT TGIQEDADRR VSQNSLGEMT KLGSKTALNR
   901  RDTYRRRQMQ RTITRQMSFD LTKLLVTEDW FSDISPQTMR RLLNIVSVTG RLLRANQISF
   961  NWDRLASWIN LTEQWPYRTS WLILYLEETE GIPDQMTLKT IYERISKNIP TTKDVEPLLE
  1021  IDGDIRNFEV FLSSRTPVLV ARDVKVFLPC TVNLDPKLRE IIADVRAARE QISIGGLAYP
  1081  PLPLHEGPPR APSGYSQPPS VCSSTSFNGP FAGGVVSPQP HSSYYSGMTG PQHPFYNRPF
  1141  FAPYLYTPRY YPGGSQHLIS RPSVKTSLPR DQNNGLEVIK EDAAEGLSSP TDSSRGSGPA
  1201  PGPVVLLNSL NVDAVCEKLK QIEGLDQSML PQYCTTIKKA NINGRVLAQC NIDELKKEMN
  1261  MNFGDWHLFR STVLEMRNAE SHVVPEDPRF LSESSSGPAP HGEPARRASH NELPHTELSS
  1321  QTPYTLNFSF EELNTLGLDE GAPRHSNLSW QSQTRRTPSL SSLNSQDSSI EISKLTDKVQ
  1381  AEYRDAYREY IAQMSQLEGG PGSTTISGRS SPHSTYYMGQ SSSGGSIHSN LEQEKGKDSE
  1441  PKPDDGRKSF LMKRGDVIDY SSSGVSTNDA SPLDPITEED EKSDQSGSKL LPGKKSSERS
  1501  SLFQTDLKLK GSGLRYQKLP SDEDESGTEE SDNTPLLKDD KDRKAEGKVE RVPKSPEHSA
  1561  EPIRTFIKAK EYLSDALLDK KDSSDSGVRS SESSPNHSLH NEVADDSQLE KANLIELEDD
  1621  SHSGKRGIPH SLSGLQDPII ARMSICSEDK KSPSECSLIA SSPEENWPAC QKAYNLNRTP
  1681  STVTLNNNSA PANRANQNFD EMEGIRETSQ VILRPSSSPN PTTIQNENLK SMTHKRSQRS
  1741  SYTRLSKDPP ELHAAASSES TGFGEERESI L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KIDINS220 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

4

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

40 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KIDINS220.

Disease | AllUniProt

Conditions KIDINS220 is implicated in, by any mechanism.

• Spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) MIM:617296
• Ventriculomegaly and arthrogryposis (VENARG) MIM:619501

Disease | GeneticClinVar

58 pathogenic / likely-pathogenic of 1,175 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spastic paraplegia, intellectual disability, nystagmus, and obesity
• KIDINS220-related disorder
• Ventriculomegaly and arthrogryposis
• Inborn genetic diseases
• Cerebral palsy

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)

0.35

gnomAD pLI

0.07

gnomAD missense Z

2.26

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to nerve growth factor stimulus
• dendrite morphogenesis
• in utero embryonic development
• nerve growth factor signaling pathway
• positive regulation of neuron projection development

Molecular functions

• PDZ domain binding
• protein kinase regulator activity

Cellular components

• cytosol
• late endosome
• membrane
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Ankyrin repeat
• KAP family P-loop domain
• Sterile alpha motif/pointed domain superfamily
• Ankyrin repeat-containing domain superfamily
• Ankyrin repeat
• KAP family P-loop domain
• Ankyrin repeats (3 copies)
• Neurotrophin-activated signaling adaptor
• Kinase D-interacting substrate of 220 kDa-like, SAM domain
• Kinase D-interacting substrate of 220 kDa-like, SAM domain-like

KeywordsUniProt

• ANK repeat
• Endosome
• Hereditary spastic paraplegia
• Intellectual disability
• Membrane
• Neurodegeneration
• Neurogenesis
• Obesity
• Phosphoprotein
• Repeat
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of KIDINS220 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EPHA4
• ERKL
• NGFR
• NTRK1
• NTRK2
• NTRK3
• PRKD1
• RAPGEF2