Atlas of Genetics and Cytogenetics in Oncology and Haematology

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ARNT (aryl hydrocarbon receptor nuclear translocator)

Written2004-10Oliver Hankinson
UCLA Medical Center, Center for the Health Sciences, Box 951732,Los Angeles, CA 90095-1732, USA

(Note : for Links provided by Atlas : click)


Other aliasHIF-1b
LocusID (NCBI) 405
Atlas_Id 223
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at and ends at bp from pter
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ARNT (1q21.3) / ARNT (1q21.3)ARNT (1q21.3) / CRISPLD2 (16q24.1)ARNT (1q21.3) / CTSK (1q21.3)
ARNT (1q21.3) / ETV6 (12p13.2)ARNT (1q21.3) / F5 (1q24.2)ARNT (1q21.3) / MTRNR2L1 (17p11.2)
ARNT (1q21.3) / RIIAD1 (1q21.3)COL1A1 (17q21.33) / ARNT (1q21.3)ETV6 (12p13.2) / ARNT (1q21.3)
RRNAD1 (1q23.1) / ARNT (1q21.3)


Note The gene is about 65 kb in size and has 22 exons.
Transcription Five alternative transcriptional start sites have been identified, located from 27 to 147 nucleotides 5' to the ATG translational initiation codon. There are two alternative polyadenylation sites, giving rise to transcripts of about 2,600 and 4,200 nucleotides. The 45 nucleotide exon 5 is an alternative exon and is spliced out in approximately half of the transcripts. This proportion does not seem to vary much between different tissues.No observable effects on the resulting protein due to omission of exon 5 have been noted. A transcript of about 1,300 nucleotides is observed in some breast cancers and may be due to an alternative splicing event leading to elimination of the 3' end of the transcript.
Pseudogene No pseudogenes for ARNT are known.


  bHLH, basic helix-loop-helix domain; PAS, Per/ARNT/Sim homology domain; A and B, the two approximately 50 amino-acid degenerative direct repeats within the PAS domain; Q-rich, glutamine-rich transactivation domain.
Description The 87 kDa protein is comprised of 789 amino acids (if exon 5 is included) or 774 amino acids (if exon 5 is excluded).
Expression ARNT is expressed ubiquitously.
Localisation ARNT is a nuclear protein in most cell types, although it may also be located in the cytosol, particularly during embryogenesis.
Function ARNT serves as the dimerization partner for a number of other bHLH-PAS proteins, whose activity is modulated either by exogenous chemicals (the aryl hydrocarbon receptor ( AHR)), or by hypoxia (hypoxia inducible factors 1,2 and 3 alpha [HIF-1a, HIF-2a and HIF-3a), or which show restricted expression (e.g. SIM-1). The AHR/ARNT dimer activates transcription of several genes involved in metabolism of foreign chemicals, including CYP1A1, CYP1B1, and NADP(H): oxidoreductase ( NQO1). Transcriptional activation of these genes depends upon prior binding of AHR to xenobiotic ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and benzo(a)pyrene. The AHR/ARNT dimer and ARNT itself can also impact signaling by the eostrogen receptor. The HIF-1a (and 2a and 3a) proteins are stabilized and activated by hypoxia (and hypoglycemia) and activate transcription of several genes involved in adapting to these adverse conditions, including the genes for erythropoietin ( EPO), vascular endothelial growth factor ( VEGF), and a number of enzymes of glycolysis. Unlike the AHR/ARNT and HIF/ARNT dimers, the SIM-1/ARNT dimer is probably not conditionally regulated. The above dimers bind specific DNA sequences in the regulatory regions of the responsive genes. The half-site for ARNT is on the 3' side of the recognition sequence and is 5'-GTG-3'. The sequence of the other half of the binding site depends upon the identity of the dimerization partner. DNA binding of ARNT is mediated by its basic region. There is evidence that the PAS region may also be involved. Dimerization between ARNT and other bHLH-PAS proteins is mediated by their HLH and PAS regions. The transcriptional activation domain of ARNT is located towards its carboxy terminus. ARNT appears capable of binding the E-box sequence 5'-CACGTG-3', although the affinity of ARNT for itself appears relatively low and no genes responsive to the homodimer have been identified.

Homology Two ARNT-related genes, ARNT-2 and ARNT-3 (also called BMAL-1 or MOP3) have been identified. ARNT-2 is more restricted in expression than ARNT, but appears to dimerize with the same partner proteins as ARNT. ARNT-3 has a somewhat different dimerization potential than ARNT.


Germinal Several polymorphisms have been identified. None has shown an association with any disease.

Implicated in

Note Involved in a t(1;12)(q21;p13) translocation with EVT6 fusion in acute myeloblastic leukemia.
Disease Leukemia, Myelocytic, Acute AML-M2
Prognosis Unknown.
Hybrid/Mutated Gene Amino-terminal half of TEL fused to the complete coding sequence of ARNT except for its 8 amino-terminal amino acids. The reciprocal translocation probably contributes little if at all to the cancer phenotype.


Orientation of the heterodimeric aryl hydrocarbon (dioxin) receptor complex on its asymmetric DNA recognition sequence.
Bacsi SG, Reisz-Porszasz S, Hankinson O
Molecular pharmacology. 1995 ; 47 (3) : 432-438.
PMID 7700240
Recruitment of thyroid hormone receptor/retinoblastoma-interacting protein 230 by the aryl hydrocarbon receptor nuclear translocator is required for the transcriptional response to both dioxin and hypoxia.
Beischlag TV, Taylor RT, Rose DW, Yoon D, Chen Y, Lee WH, Rosenfeld MG, Hankinson O
The Journal of biological chemistry. 2004 ; 279 (52) : 54620-54628.
PMID 15485806
The basic helix-loop-helix-PAS protein ARNT functions as a potent coactivator of estrogen receptor-dependent transcription.
Brunnberg S, Pettersson K, Rydin E, Matthews J, Hanberg A, Pongratz I
Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (11) : 6517-6522.
PMID 12754377
Cloning of a factor required for activity of the Ah (dioxin) receptor.
Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA, Hankinson O
Science (New York, N.Y.). 1991 ; 252 (5008) : 954-958.
PMID 1852076
The Ah receptor nuclear translocator gene (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3.
Johnson B, Brooks BA, Heinzmann C, Diep A, Mohandas T, Sparkes RS, Reyes H, Hoffman E, Lange E, Gatti RA
Genomics. 1993 ; 17 (3) : 592-598.
PMID 8244375
Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt.
Keith B, Adelman DM, Simon MC
Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (12) : 6692-6697.
PMID 11381139
ARNT-deficient mice and placental differentiation.
Kozak KR, Abbott B, Hankinson O
Developmental biology. 1997 ; 191 (2) : 297-305.
PMID 9398442
Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT.
Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC
Nature. 1997 ; 386 (6623) : 403-407.
PMID 9121557
Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.
Ohtake F, Takeyama K, Matsumoto T, Kitagawa H, Yamamoto Y, Nohara K, Tohyama C, Krust A, Mimura J, Chambon P, Yanagisawa J, Fujii-Kuriyama Y, Kato S
Nature. 2003 ; 423 (6939) : 545-550.
PMID 12774124
Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT).
Reisz-Porszasz S, Probst MR, Fukunaga BN, Hankinson O
Molecular and cellular biology. 1994 ; 14 (9) : 6075-6086.
PMID 8065341
Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor.
Reyes H, Reisz-Porszasz S, Hankinson O
Science (New York, N.Y.). 1992 ; 256 (5060) : 1193-1195.
PMID 1317062
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.
Salomon-Nguyen F, Della-Valle V, Mauchauffe M, Busson-Le Coniat M, Ghysdael J, Berger R, Bernard OA
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (12) : 6757-6762.
PMID 10829078
Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene.
Scheel J, Hussong R, Schrenk D, Schmitz HJ
Journal of human genetics. 2002 ; 47 (5) : 217-224.
PMID 12032587
Genomic structure of the human Ah receptor nuclear translocator gene (hARNT).
Scheel J, Schrenk D
Human genetics. 2000 ; 107 (4) : 397-399.
PMID 11129342
A mutation in the aryl hydrocarbon receptor (AHR) in a cultured mammalian cell line identifies a novel region of AHR that affects DNA binding.
Sun W, Zhang J, Hankinson O
The Journal of biological chemistry. 1997 ; 272 (50) : 31845-31854.
PMID 9395531
DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins.
Swanson HI, Chan WK, Bradfield CA
The Journal of biological chemistry. 1995 ; 270 (44) : 26292-26302.
PMID 7592839
Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function.
Takagi S, Tojo H, Tomita S, Sano S, Itami S, Hara M, Inoue S, Horie K, Kondoh G, Hosokawa K, Gonzalez FJ, Takeda J
The Journal of clinical investigation. 2003 ; 112 (9) : 1372-1382.
PMID 14597763
The aryl hydrocarbon receptor nuclear transporter is modulated by the SUMO-1 conjugation system.
Tojo M, Matsuzaki K, Minami T, Honda Y, Yasuda H, Chiba T, Saya H, Fujii-Kuriyama Y, Nakao M
The Journal of biological chemistry. 2002 ; 277 (48) : 46576-46585.
PMID 12354770
Patent ductus venosus and dioxin resistance in mice harboring a hypomorphic Arnt allele.
Walisser JA, Bunger MK, Glover E, Harstad EB, Bradfield CA
The Journal of biological chemistry. 2004 ; 279 (16) : 16326-16331.
PMID 14764592
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
Wang GL, Jiang BH, Rue EA, Semenza GL
Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (12) : 5510-5514.
PMID 7539918
Aryl hydrocarbon (Ah) nonresponsiveness in estrogen receptor-negative MDA-MB-231 cells is associated with expression of a variant arnt protein.
Wilson CL, Thomsen J, Hoivik DJ, Wormke MT, Stanker L, Holtzapple C, Safe SH
Archives of biochemistry and biophysics. 1997 ; 346 (1) : 65-73.
PMID 9328285
The role of the aryl hydrocarbon receptor nuclear translocator (ARNT) in hypoxic induction of gene expression. Studies in ARNT-deficient cells.
Wood SM, Gleadle JM, Pugh CW, Hankinson O, Ratcliffe PJ
The Journal of biological chemistry. 1996 ; 271 (25) : 15117-15123.
PMID 8662957


This paper should be referenced as such :
Hankinson, O
ARNT (aryl hydrocarbon receptor nuclear translocator)
Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):305-307.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  t(1;12)(q21;p13) ETV6/ARNT
t(1;12)(q21;p13) ETV6/ARNT

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ]
  ARNT/RIIAD1 (1q21)
t(1;1)(q21;q23) RRNAD1/ARNT
t(1;1)(q21;q24) ARNT/F5

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)405
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 18 17:28:36 CEST 2018

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