Atlas of Genetics and Cytogenetics in Oncology and Haematology

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RARRES1 (retinoic acid receptor responder (tazarotene induced) 1)

Written2007-01Kwok-Wai Lo, Grace TY Chung
State Key Laboratory in Cancer in South China, Department of Anatomical and Cellular Pathology, Prinve of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

(Note : for Links provided by Atlas : click)


Alias (NCBI)TIG1
HGNC Alias symbTIG1
HGNC Alias namelatexin-like
HGNC Previous nameretinoic acid receptor responder (tazarotene induced) 1
LocusID (NCBI) 5918
Atlas_Id 42050
Location 3q25.32  [Link to chromosome band 3q25]
Location_base_pair Starts at 158696892 and ends at 158732457 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RARRES1.png]
Local_order Telomeric to MFSD1 and centromeric to GFM1 and LXN
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DDX24 (14q32.12) / RARRES1 (3q25.32)GFM1 (3q25.32) / RARRES1 (3q25.32)RARRES1 (3q25.32) / RARRES1 (3q25.32)
Note RARRES1 (retinoic acid receptor responder 1) is also known as TIG1 (Tazarotene-induced gene 1). The gene was initially identified as a target gene that was induced by the synthetic retinoid tazarotene (AGN 190168) in human skin raft cultures. It is upregulated by retinoic acid receptor specific but not by retinoid X receptor-specific retinoids.
As noted in the early published articles, the authors mentioned that RARRES1 (TIG1) is located at 3p12-13. The location was subsequently confirmed to be incorrect. UCSC Genome Browser on Human Mar. 2006 Assembly shows that the RARRES1 should be located between 3q25.32 and 3q25.33.


  Two transcript variants (isoform 1: NM_206963.1 and isoform 2: NM_002888.2) are shown. Black boxes represent the exons of RARRES1. CpG: location of CpG island.
Description The RARRES1 gene contains 6 exons and spans 35377 bases.
Transcription Two alternatively spliced transcripts were identified (isoform 1 and isoform 2). Exons 1 to 4 are common to both isoforms. Exon 5 and 6 are present in isoform 1 (NM_206963.1) only. The cDNA of isoform 1 is 1545 bp while isoform 2 is 886 bp.
Pseudogene No known pseudogenes


  The gray box indicates the single membrane-spanning hydrophobic region. Lataxin domain for 2 RARRES1 isoforms is shown as black box.
Description Called Retinoic acid receptor responder protein 1 (synonyms: Tazarotene-induced gene 1 protein/RAR-responsive protein TIG1); Two isoform, isoform 1 (NP_996846) and isoform 2 (NP_002879), produced by alternative splicing were reported. Isoforms 1 and 2 contain 294 and 228 amino acids respectively. Molecular weight of Isoform 1 is 33258 Da. The two isoforms show difference in the 3'end-region. RARRES1 is predicted to be a transmembrane protein with a small N-terminal intracellular regions, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal.
Expression High level of RARRES1 transcripts was detected in multiple tissues including prostate, heart, lung, liver, colon and small intestine. Expression of RARRES1 protein was demonstrated in colorectal tissues.
Localisation Based on the predicted amino acid sequence, RARRES1 is suspected to be a transmembrane protein. However, immunohistochemical analysis showed that RARRES1 protein localizes at the supranuclear regions of colorectal adenocarcinoma, adenoma and adjacent normal epithelial cells. The precise localization of RARRES1 protein needed to be further investigated.
Function RARRES1 was suggested to be a tumor suppressor of a variety of human cancers. Inactivation of RARRES1 is involved in the malignant progression of prostate cancer. Restoration of RARRES1 expression in malignant prostate cell lines led to a decrease of invasiveness and tumorigenicity in nude mice. It is speculated that RARRES1 may function as a cell adhesion molecule. Since the protein shows sequence similarity to Latexin, the only known mammalian carboxypeptidase inhibitor, RARRES1 may also have protease inhibitor activity and inhibit the degradation of extracellular matrix.
Homology RARRES1 belongs to the proteinase inhibitor I47 (latexin) family, its c-terminal region shows 30% sequence similarity with Latexin.


Note No germline or somatic mutation associated with disease is reported.

Implicated in

Entity A variety of human cancers
Note The association of RARRES1 with human cancer was first revealed by the subtractive differential gene display analysis of benign and malignant prostate cell lines. The gene was expressed in benign prostate cell lines and not in malignant ones. It is now considered as a putative tumor suppressor gene in a variety of human cancers although its function remains unclear. Its expression is commonly suppressed in prostate carcinoma, lung cancer, nasopharyngeal carcinoma, and leukemia by promoter hypermethylation. Restoring RARRES1 expression in prostate cancer cells resulted in decrease of in vitro invasiveness and in vivo tumorigenicity. RARRES1 also implicated in therapeutic effects of retinoic acid in psoriasis.
Disease prostate carcinoma, nasopharyngeal carcinoma, head and neck cancer, lung cancer, gastric carcinoma, colorectal adenocarcinoma, endometrial cancer, breast cancer, acute myeloid leukemia, Chronic myeloid leukemia.
Prognosis down-regulation of RARRES1 is significantly related with the late stage colorectal adenocarcinoma (Dukes's stage D). However, no difference in survival was found comparing patient with negative, weak and strong RARRES1 expression in tumors.
Cytogenetics No translocations and amplifications of this gene have been reported
Hybrid/Mutated Gene No hybrid gene involving RARRES1 has been described.


Note No breakpoints involving this gene have been described.


An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1.
Aagaard A, Listwan P, Cowieson N, Huber T, Ravasi T, Wells CA, Flanagan JU, Kellie S, Hume DA, Kobe B, Martin JL
Structure (London, England : 1993). 2005 ; 13 (2) : 309-317.
PMID 15698574
Molecular mechanisms of tazarotene action in psoriasis.
Duvic M, Nagpal S, Asano AT, Chandraratna RA
Journal of the American Academy of Dermatology. 1997 ; 37 (2 Pt 3) : S18-S24.
PMID 9270552
Ovocalyxin-32, a novel chicken eggshell matrix protein. isolation, amino acid sequencing, cloning, and immunocytochemical localization.
Gautron J, Hincke MT, Mann K, Panheleux M, Bain M, McKee MD, Solomon SE, Nys Y
The Journal of biological chemistry. 2001 ; 276 (42) : 39243-39252.
PMID 11493603
Purification of ovocalyxin-32, a novel chicken eggshell matrix protein.
Hincke MT, Gautron J, Mann K, Panhéleux M, McKee MD, Bain M, Solomon SE, Nys Y
Connective tissue research. 2003 ; 44 Suppl 1 : 16-19.
PMID 12952168
Tazarotene-induced gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity.
Jing C, El-Ghany MA, Beesley C, Foster CS, Rudland PS, Smith P, Ke Y
Journal of the National Cancer Institute. 2002 ; 94 (7) : 482-490.
PMID 11929948
Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma.
Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP
International journal of cancer. Journal international du cancer. 2005 ; 113 (3) : 386-392.
PMID 15455391
Is TIG1 a new tumor suppressor in prostate cancer?
Lotan R
Journal of the National Cancer Institute. 2002 ; 94 (7) : 469-470.
PMID 11929940
DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage.
Mizuiri H, Yoshida K, Toge T, Oue N, Aung PP, Noguchi T, Yasui W
Cancer science. 2005 ; 96 (9) : 571-577.
PMID 16128742
Microdissection, mRNA amplification and microarray: a study of pleural mesothelial and malignant mesothelioma cells.
Mohr S, Bottin MC, Lannes B, Neuville A, Bellocq JP, Keith G, Rihn BH
Biochimie. 2004 ; 86 (1) : 13-19.
PMID 14987796
Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin.
Nagpal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA
The Journal of investigative dermatology. 1996 ; 106 (2) : 269-274.
PMID 8601727
Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy.
Rosenbaum E, Hoque MO, Cohen Y, Zahurak M, Eisenberger MA, Epstein JI, Partin AW, Sidransky D
Clinical cancer research : an official journal of the American Association for Cancer Research. 2005 ; 11 (23) : 8321-8325.
PMID 16322291
DNA methylation of genes linked with retinoid signaling in gastric carcinoma: expression of the retinoid acid receptor beta, cellular retinol-binding protein 1, and tazarotene-induced gene 1 genes is associated with DNA methylation.
Shutoh M, Oue N, Aung PP, Noguchi T, Kuraoka K, Nakayama H, Kawahara K, Yasui W
Cancer. 2005 ; 104 (8) : 1609-1619.
PMID 16134180
Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia.
So K, Tamura G, Honda T, Homma N, Waki T, Togawa N, Nishizuka S, Motoyama T
Cancer science. 2006 ; 97 (11) : 1155-1158.
PMID 16952303
Discovery of epigenetically masked tumor suppressor genes in endometrial cancer.
Takai N, Kawamata N, Walsh CS, Gery S, Desmond JC, Whittaker S, Said JW, Popoviciu LM, Jones PA, Miyakawa I, Koeffler HP
Molecular cancer research : MCR. 2005 ; 3 (5) : 261-269.
PMID 15886297
Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma.
Tokumaru Y, Harden SV, Sun DI, Yamashita K, Epstein JI, Sidransky D
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (16) : 5518-5522.
PMID 15328191
Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue.
Wilson CL, Sims AH, Howell A, Miller CJ, Clarke RB
Endocrine-related cancer. 2006 ; 13 (2) : 617-628.
PMID 16728587
DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line.
Wood RJ, Tchack L, Angelo G, Pratt RE, Sonna LA
Physiological genomics. 2004 ; 17 (2) : 122-129.
PMID 14996990
RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma.
Wu CC, Shyu RY, Chou JM, Jao SW, Chao PC, Kang JC, Wu ST, Huang SL, Jiang SY
European journal of cancer (Oxford, England : 1990). 2006 ; 42 (4) : 557-565.
PMID 16426842
Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers.
Youssef EM, Chen XQ, Higuchi E, Kondo Y, Garcia-Manero G, Lotan R, Issa JP
Cancer research. 2004 ; 64 (7) : 2411-2417.
PMID 15059893
Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene.
Zhang J, Liu L, Pfeifer GP
Oncogene. 2004 ; 23 (12) : 2241-2249.
PMID 14691453
All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo.
Zirn B, Samans B, Spangenberg C, Graf N, Eilers M, Gessler M
Oncogene. 2005 ; 24 (33) : 5246-5251.
PMID 15897880


This paper should be referenced as such :
Chung, GTY ; Lo, KW
RARRES1 (retinoic acid receptor responder (tazarotene induced) 1)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):121-123.
Free journal version : [ pdf ]   [ DOI ]

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  GFM1/RARRES1 (3q25)

External links

HGNC (Hugo)RARRES1   9867
Entrez_Gene (NCBI)RARRES1    retinoic acid receptor responder 1
AliasesLXNL; PERG-1; TIG1
GeneCards (Weizmann)RARRES1
Ensembl hg19 (Hinxton)ENSG00000118849 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000118849 [Gene_View]  ENSG00000118849 [Sequence]  chr3:158696892-158732457 [Contig_View]  RARRES1 [Vega]
ICGC DataPortalENSG00000118849
Genatlas (Paris)RARRES1
Genetics Home Reference (NIH)RARRES1
Genomic and cartography
GoldenPath hg38 (UCSC)RARRES1  -     chr3:158696892-158732457 -  3q25.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RARRES1  -     3q25.32   [Description]    (hg19-Feb_2009)
GoldenPathRARRES1 - 3q25.32 [CytoView hg19]  RARRES1 - 3q25.32 [CytoView hg38]
genome Data Viewer NCBIRARRES1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK130079 AW514087 BC029640 BM919188 U27185
RefSeq transcript (Entrez)NM_002888 NM_206963
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RARRES1
Alternative Splicing GalleryENSG00000118849
Gene Expression Viewer (FireBrowse)RARRES1 [ Firebrowse - Broad ]
GenevisibleExpression of RARRES1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5918
GTEX Portal (Tissue expression)RARRES1
Human Protein AtlasENSG00000118849-RARRES1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP49788   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP49788  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP49788
Splice isoforms : SwissVarP49788
Domains : Interpro (EBI)Prot_inh_latexin    TAG1   
Domain families : Pfam (Sanger)Latexin (PF06907)   
Domain families : Pfam (NCBI)pfam06907   
Conserved Domain (NCBI)RARRES1
Blocks (Seattle)RARRES1
Human Protein Atlas [tissue]ENSG00000118849-RARRES1 [tissue]
Peptide AtlasP49788
IPIIPI00410240   IPI00410377   IPI00946313   
Protein Interaction databases
IntAct (EBI)P49788
Ontologies - Pathways
Ontology : AmiGOextracellular space  metalloendopeptidase inhibitor activity  negative regulation of cell proliferation  negative regulation of endopeptidase activity  integral component of membrane  extracellular exosome  
Ontology : EGO-EBIextracellular space  metalloendopeptidase inhibitor activity  negative regulation of cell proliferation  negative regulation of endopeptidase activity  integral component of membrane  extracellular exosome  
Atlas of Cancer Signalling NetworkRARRES1
Wikipedia pathwaysRARRES1
Orthology - Evolution
GeneTree (enSembl)ENSG00000118849
Phylogenetic Trees/Animal Genes : TreeFamRARRES1
Homologs : HomoloGeneRARRES1
Homology/Alignments : Family Browser (UCSC)RARRES1
Gene fusions - Rearrangements
Fusion : Fusion_HubDDX24--RARRES1    IFT80--RARRES1    RARRES1--RARRES1    RARRES1--RSRC1    RARRES1--TOMM70A   
Fusion : QuiverRARRES1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRARRES1 [hg38]
Exome Variant ServerRARRES1
GNOMAD BrowserENSG00000118849
Varsome BrowserRARRES1
Genomic Variants (DGV)RARRES1 [DGVbeta]
DECIPHERRARRES1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRARRES1 
ICGC Data PortalRARRES1 
TCGA Data PortalRARRES1 
Broad Tumor PortalRARRES1
OASIS PortalRARRES1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRARRES1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DRARRES1
Mutations and Diseases : HGMDRARRES1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RARRES1
DgiDB (Drug Gene Interaction Database)RARRES1
DoCM (Curated mutations)RARRES1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RARRES1 (select a term)
NCG6 (London) select RARRES1
Cancer3DRARRES1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry RARRES1
NextProtP49788 [Medical]
Target ValidationRARRES1
Huge Navigator RARRES1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA34228
Clinical trialRARRES1
canSAR (ICR)RARRES1 (select the gene name)
DataMed IndexRARRES1
PubMed34 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 17:58:57 CET 2021

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