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ALK ALK receptor tyrosine kinase [ Homo sapiens (human) ]

Gene ID: 238, updated on 2-Nov-2024

Summary

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Official Symbol
ALKprovided by HGNC
Official Full Name
ALK receptor tyrosine kinaseprovided by HGNC
Primary source
HGNC:HGNC:427
See related
Ensembl:ENSG00000171094 MIM:105590; AllianceGenome:HGNC:427
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
ALK1; CD246; NBLST3
Summary
This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011]
Expression
Low expression observed in reference dataset See more
Orthologs
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Genomic context

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See ALK in Genome Data Viewer
Location:
2p23.2-p23.1
Exon count:
29
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (29192774..29921586, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (29236229..29965553, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (29415640..30144452, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105374386 Neighboring gene CLIP4 5' region CAGE-defined mid-level expression enhancer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11319 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11320 Neighboring gene uncharacterized LOC124907747 Neighboring gene CAP-Gly domain containing linker protein family member 4 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:29474025-29474526 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:29474527-29475026 Neighboring gene uncharacterized LOC101929386 Neighboring gene Sharpr-MPRA regulatory region 127 Neighboring gene uncharacterized LOC105374389 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:29729319-29729514 Neighboring gene Sharpr-MPRA regulatory region 9206 Neighboring gene NANOG hESC enhancer GRCh37_chr2:29827351-29827900 Neighboring gene RNA, 7SL, cytoplasmic 516, pseudogene Neighboring gene uncharacterized LOC124907748 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:30117944-30118493 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:30123496-30124120 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:30124121-30124745 Neighboring gene NANOG hESC enhancer GRCh37_chr2:30167172-30167673 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:30186510-30187010 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:30187011-30187511 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:30188897-30189398 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:30189399-30189898 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:30248848-30249348 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15532 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11321 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11322 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11323 Neighboring gene uncharacterized LOC105374414 Neighboring gene small nucleolar RNA, H/ACA box 10B Neighboring gene yippee like 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. Are there imaging characteristics associated with lung adenocarcinomas harboring ALK rearrangements? Halpenny DF, et al. Lung Cancer, 2014 Nov. PMID 25312988, Free PMC Article
  2. Detection of ALK protein expression in lung squamous cell carcinomas by immunohistochemistry. Wang J, et al. J Exp Clin Cancer Res, 2014 Dec 21. PMID 25527865, Free PMC Article
  3. Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer. Park G, et al. Endocr Relat Cancer, 2015 Feb. PMID 25527510
  4. ALK testing in lung adenocarcinoma: technical aspects to improve FISH evaluation in daily practice. Martin V, et al. J Thorac Oncol, 2015 Apr. PMID 25514802
  5. A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Chou A, et al. Am J Surg Pathol, 2015 May. PMID 25501013, Free PMC Article

See all (830) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.
    Title: Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.
  2. Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm.
    Title: Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm.
  3. Mucinous epidermoid carcinoma of the lung with ALK mutation: Case report and literature review.
    Title: Mucinous epidermoid carcinoma of the lung with ALK mutation: Case report and literature review.
  4. Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.
    Title: Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.
  5. [ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases].
    Title: [ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases].
  6. ALK upregulates POSTN and WNT signaling to drive neuroblastoma.
    Title: ALK upregulates POSTN and WNT signaling to drive neuroblastoma.
  7. Dissecting the role of ALK double mutations in drug resistance to lorlatinib with in-depth theoretical modeling and analysis.
    Title: Dissecting the role of ALK double mutations in drug resistance to lorlatinib with in-depth theoretical modeling and analysis.
  8. Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.
    Title: Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.
  9. Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).
    Title: Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).
  10. The acetylation of STAT3 at K685 attenuates NPM-ALK-induced tumorigenesis.
    Title: The acetylation of STAT3 at K685 attenuates NPM-ALK-induced tumorigenesis.
Submit: New GeneRIF Correction See all GeneRIFs (775)

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
Neuroblastoma, susceptibility to, 3
MedGen: C2751681 OMIM: 613014 GeneReviews: ALK-Related Neuroblastic Tumor Susceptibility
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2019-12-20)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2019-12-20)

ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 Nef and ALK show similar effects by increasing different cytokines/chemokines, such as IL-1beta, TNF-alpha, and RANTES, that may be relevant for HAD pathogenesis PubMed
nef Overexpression of HIV-1 Nef and ALK effect gelatinase activation in astrocytic glioma cells PubMed
nef HIV-1 Nef and ALK are capable of cumulatively influencing the MAP-K phosphorylation in astrocytic glioma cells PubMed
nef HIV-1 Nef and anaplastic lymphoma kinase (ALK) do not physically interact but ALK expression is upregulated by Nef in astrocytic glioma cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables heparin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein tyrosine kinase activity TAS
Traceable Author Statement
more info
  
enables receptor signaling protein tyrosine kinase activator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transmembrane receptor protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables transmembrane receptor protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transmembrane receptor protein tyrosine kinase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in adult behavior IEA
Inferred from Electronic Annotation
more info
  
involved_in cell surface receptor protein tyrosine kinase signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cell surface receptor protein tyrosine kinase signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in energy homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in hippocampus development IEA
Inferred from Electronic Annotation
more info
  
involved_in multicellular organism development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of lipid catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in neuron development TAS
Traceable Author Statement
more info
 PubMed 
involved_in peptidyl-tyrosine autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of dendrite development ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autophosphorylation TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of cell population proliferation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of dopamine receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in response to environmental enrichment IEA
Inferred from Electronic Annotation
more info
  
involved_in response to stress IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in swimming behavior IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in extracellular exosome HDA PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
ALK tyrosine kinase receptor
Names
CD246 antigen
anaplastic lymphoma receptor tyrosine kinase
mutant anaplastic lymphoma kinase
NP_001340694.1
NP_004295.2
XP_054197220.1

NCBI Reference Sequences (RefSeq)

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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.

Genomic

  1. NG_009445.1 RefSeqGene

    Range
    4956..733793
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_488

mRNA and Protein(s)

  1. NM_001353765.2 → NP_001340694.1  ALK tyrosine kinase receptor isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. The promoter and 5' terminal exon sequence is from an endogenous retroviral LTR (PMID: 26444240). The resulting isoform (2, also known as ALKATI) is shorter and has a distinct N-terminus, compared to isoform 1. The encoded protein is expressed in melanoma cells.
    Source sequence(s)
    LN864494
    Consensus CDS
    CCDS86828.1
    UniProtKB/TrEMBL
    A0A0K2YUJ3
    Related
    ENSP00000493203.1, ENST00000642122.1
    Conserved Domains (1) summary
    cd05036
    Location:41 → 317
    PTKc_ALK_LTK; Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase

  2. NM_004304.5 → NP_004295.2  ALK tyrosine kinase receptor isoform 1 precursor

    See identical proteins and their annotated locations for NP_004295.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    DA455128, EU788004, U62540
    Consensus CDS
    CCDS33172.1
    UniProtKB/Swiss-Prot
    A6P4T4, A6P4V4, Q4ZFX9, Q53QQ6, Q53RZ4, Q59FI3, Q9UM73, Q9Y4K6
    UniProtKB/TrEMBL
    B6D4Y1, B6D4Y2, B6D4Y3, B6D4Y5, B6D4Y6, B6D4Y7, B6D4Y8, D1MAM0, D1MAM1, D1MAM2, D1MAM3, D1MAM4, D1MAM5, F0UY65, F0UY66
    Related
    ENSP00000373700.3, ENST00000389048.8
    Conserved Domains (6) summary
    cd06263
    Location:480 → 631
    MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...
    smart00192
    Location:441 → 467
    LDLa; Low-density lipoprotein receptor domain class A
    cd05036
    Location:1109 → 1385
    PTKc_ALK_LTK; Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase
    pfam00629
    Location:480 → 636
    MAM; MAM domain, meprin/A5/mu
    pfam07714
    Location:1116 → 1383
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14670
    Location:987 → 1021
    FXa_inhibition; Coagulation Factor Xa inhibitory site

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_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    29192774..29921586 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_001738688.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    29236229..29965553 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341245.1 → XP_054197220.1  ALK tyrosine kinase receptor isoform X1

RNA

  1. XR_008486309.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UM73.3 GenPept UniProtKB/Swiss-Prot:Q9UM73

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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