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Symbol ALK contributors: mct/shn - updated : 14-11-2013
HGNC name anaplastic lymphoma receptor tyrosine kinase
HGNC id 427
Corresponding disease
ALCL ALK-positive anaplastic large-cell lymphoma
IMT inflammatory myofibroblastic tumor
NBL2 neuroblastoma
Location 2p23.2      Physical location : 29.415.640 - 30.144.432
Synonym name
  • anaplastic lymphoma kinase (Ki-1)
  • CD246 antigen
  • ALK tyrosine kinase receptor
  • TRK-fused gene-anaplastic lymphoma kinase fusion protein
  • mutant anaplastic lymphoma kinase
  • Synonym symbol(s) CD246, TFG/ALK, Ki-1, NBLST3
    TYPE functioning gene
    STRUCTURE 728.80 kb     29 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    MAPPING cloned Y linked N status confirmed
    Map pter - D2S392 - D2S170 - ALK - D2S2383 - D2S375 - cen
    Physical map
    FRCP1 GCKR 2p23.3-p23.2 glucokinase (hexokinase 4) regulatory protein DKFZp434G118 ZNF512 2p23 zinc finger protein 512 FLJ13646 2p23.3 hypothetical protein FLJ13646 XAB1 2p23.3 XPA binding protein 1 STAF65(gamma) 2pter-p25.1 SPTF-associated factor 65 gamma SLC4A1AP 2p23.3 solute carrier family 4 (anion exchanger), member 1, adaptor protein MRPL33 2p22 mitochondrial ribosomal protein L33 RBSK BRE 2p23.3 brain and reproductive organ-expressed (TNFRSF1A modulator) FOSL2 2p23-p22 FOS-like antigen 2 FLJ23306 2p23.3 hypothetical protein FLJ23306 LOC388937 2 similar to Phospholipase PLB PPP1CB 2p23 protein phosphatase 1, catalytic subunit, beta isoform SPY1 2p23.3 speedy FLJ20628 2p23.3 hypothetical protein FLJ20628 KIAA0007 2p23.3 KIAA0007 protein LOC388938 2 LOC388938 LOC165186 2p23.3 similar to RIKEN cDNA 4632412N22 gene LOC388939 2 similar to BC027072 protein FLJ21069 2p23.3 hypothetical protein FLJ21069 ALK 2p23 anaplastic lymphoma kinase (Ki-1) CGI-127 2p23.3 yippee protein LBH 2p23.3 likely ortholog of mouse limb-bud and heart gene FLJ37965 CAPN13 2p22-p21 likely ortholog of mouse limb-bud and heart gene
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 6222 176.3 1620 - 2008 18923524
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     mouthtongue  moderately
    Reproductivefemale systemovary  predominantly
     male systemtestis   
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    Text essentially and transiently expressed during development of the central and peripheral nervous system
  • two MAM domain
  • one tyrosine kinase catalytic domain
  • one LDL receptor class A domain
  • nine phosphotyrosine
  • conjugated GlycoP
    mono polymer homomer , dimer
    interspecies ortholog to Alk, Rattus norvegicus
    ortholog to Alk, Mus musculus
    ortholog to alk, Danio rerio
    ortholog to ALK, pan troglodytes
    intraspecies homolog to LTK
  • TYR protein kinases family
  • insulin receptor subfamily
  • CATEGORY protooncogene , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    text single-pass type I membrane protein
    basic FUNCTION
  • acting as an orphan receptor with a tyrosine-protein kinase activity
  • involved in the normal development and function of the nervous system
  • involved in activation of RAP1GDS1 that may contribute to cell proliferation and oncogenesis of neuroblastoma driven by gain-of-function mutant ALK receptors
  • critical player in neuroblastoma development
    text important role in brain development
    signaling signal transduction
    a component
  • N-glycosylated
  • homodimer, when bound to ligand
    small molecule nucleotide,
  • ATP
  • zinc could constitute an endogenous ligand of ALK in vertebrates
  • interacting with PHOX2B (PHOX2B drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target)
  • protein
  • CD30
  • Pleiotrophin, PTN
  • Jak3
  • Midkine, MK
  • ShcC
  • NIPA
  • Grb2, SOCS1, SOCS5, IRS4, Rho-GTPase-activating protein, RAB35, MAP kinase 1, MEK kinase 1,4 and 5, PKC, MLCK, EphA1, ephrinB, JNK kinase 2, cyclin G-associated kinase, meprin, PTPK, protein phosphatase 2 subunit, Hsp60 precursor, PLCitalic gamma1, Jak2, Jak3, Stat3, and IRS, lamin B1RAD17 homolog
  • ALK stimulates initiation of transcription of the MYCN gene
  • cell & other
    activated by zinc (activation is dependent of ALK tyrosine kinase activity and dimerization of the receptor but is independent of Src family kinase activity)
    Phosphorylated by PTN/RPTPbeta/zeta signaling pathway
    corresponding disease(s) IMT , ALCL , NBL2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion translocation    
    fused with SEC31L1, in a translocation t(2;4)(p23;q21), in an intraabdominal inflammatory myofibroblastic tumor
    tumoral   translocation    
    translocation t(2;5)(p23;q35),(see NPM1) in anaplastic nodal non Hodgkin lymphoma and B cell lymphoma
    tumoral   inversion    
    inv(2)(p23;q35)in anaplastic large-cell lymphoma
    tumoral fusion      
    with EML4 in non-small-cell lung cancer
    tumoral germinal mutation      
    in most hereditary neuroblastomas
    tumoral somatic mutation     gain of function
    activating mutations can be somatically acquired in neuroblastoma
    tumoral       gain of function
    in neuroblastoma
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments (ALK-specific kinase inhibitors might improve its clinical outcome)
  • SystemTypeDisorderPubmed
    ALK inhibitors may provide a means to control NSCLC in the latter population of patients
    identification of the downstream effector pathways controlled by ALK should pave the way for the rational design of ALK-inhibition therapies for the treatment of a subset of human cancers that harbor ALK aberrations
    germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for the neuroblastoma, lethal paediatric malignancy
    inhibition of ALK kinase activity results in anti-tumoural efficacy
  • Forced expression of wild-type ALK and Neuroblastoma-related constitutively active ALK mutants in cultures of proliferating immature sympathetic neurons results in a strong proliferation increase, whereas Alk knockdown and pharmacological inhibition of Alk activity decrease proliferation
  • in vivo inhibition of Alk signaling by virus-mediated shRNA knockdown of Alk and Midkine leads to strongly reduced sympathetic neuron proliferation