TIMELESS Gene

Name timeless circadian clock
Description The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTIMELESS is a multifunctional protein originally identified through its role in the circadian clock in Drosophila and subsequently shown to be highly conserved in mammals. Although its function in the core oscillator remains debated, TIMELESS interacts with key clock components—such as cryptochrome and period proteins—and has been implicated in the regulation of sleep–wake cycles, mood, and seasonal behavior. Genetic association studies have linked polymorphisms in TIMELESS with major mood disorders, bipolar disorder, depression with sleep disturbances, and even alcohol abuse, supporting the concept that clock gene dysfunction may contribute to neuropsychiatric phenotypes and altered circadian timing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its circadian facets, TIMELESS is essential for maintaining genomic integrity through its pivotal roles at the DNA replication fork. It forms a stable complex with Tipin and associates with the replisome to facilitate efficient fork progression, mediate replication checkpoint responses, and promote proper phosphorylation of checkpoint kinases such as CHK1 and ATM/CHK2. In response to DNA damage—including UV‐induced lesions—TIMELESS cooperates with other replication and repair factors (for example, PARP1) to protect stalled forks and ensure accurate DNA synthesis, thereby preventing chromosome instability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTIMELESS further contributes to genome stability by regulating replication–termination processes, ensuring proper sister chromatid cohesion, and preserving telomere integrity. Its elevated expression in cancer cells appears to confer increased tolerance to oncogene‐induced replication stress, while its dysregulation is associated with tumor progression and adverse clinical outcome in several cancers—including prostate, lung, and breast carcinomas. Moreover, emerging evidence points to a role for TIMELESS in recognizing challenging DNA secondary structures (such as G-quadruplexes), thereby coordinating replication with DNA repair and chromosomal cohesion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Virginia Soria, Erika Martínez-Amorós, Geòrgia Escaramís, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2009.230"}], "href": "https://doi.org/10.1038/npp.2009.230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20072116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20072116"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Keziban Unsal-Kaçmaz, Thomas E Mullen, William K Kaufmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coupling of human circadian and cell cycles by the timeless protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.8.3109-3116.2005"}], "href": "https://doi.org/10.1128/MCB.25.8.3109-3116.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15798197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15798197"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "H A Mansour, J Wood, T Logue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2005.00147.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2005.00147.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16507006"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16507006"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jiajun Shi, Jacqueline K Wittke-Thompson, Judith A Badner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30714"}], "href": "https://doi.org/10.1002/ajmg.b.30714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18228528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18228528"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hader A Mansour, Michael E Talkowski, Joel Wood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bipolar Disord (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-5618.2009.00756.x"}], "href": "https://doi.org/10.1111/j.1399-5618.2009.00756.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19839995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19839995"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Leena Kovanen, Sirkku T Saarikoski, Jari Haukka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Alcohol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/alcalc/agq035"}], "href": "https://doi.org/10.1093/alcalc/agq035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20554694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20554694"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ani Englund, Leena Kovanen, Sirkku T Saarikoski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NPAS2 and PER2 are linked to risk factors of the metabolic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Circadian Rhythms (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1740-3391-7-5"}], "href": "https://doi.org/10.1186/1740-3391-7-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19470168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19470168"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Siddheshwar J Utge, Pia Soronen, Anu Loukola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0009259"}], "href": "https://doi.org/10.1371/journal.pone.0009259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20174623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20174623"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Louise K Sjöholm, Leena Kovanen, Sirkku T Saarikoski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLOCK is suggested to associate with comorbid alcohol use and depressive disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Circadian Rhythms (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1740-3391-8-1"}], "href": "https://doi.org/10.1186/1740-3391-8-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20180986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20180986"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "B Etain, S Jamain, V Milhiet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between circadian genes, bipolar disorders and chronotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chronobiol Int (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/07420528.2014.906445"}], "href": "https://doi.org/10.3109/07420528.2014.906445"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24716566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24716566"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Erik Engelen, Roel C Janssens, Kazuhiro Yagita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0056623"}], "href": "https://doi.org/10.1371/journal.pone.0056623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23418588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23418588"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Keziban Unsal-Kaçmaz, Paul D Chastain, Ping-Ping Qu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02190-06"}], "href": "https://doi.org/10.1128/MCB.02190-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17296725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17296725"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Anthony L Gotter, Christine Suppa, Beverly S Emanuel "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2006.10.097"}], "href": "https://doi.org/10.1016/j.jmb.2006.10.097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17141802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17141802"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Naoko Yoshizawa-Sugata, Hisao Masai "}, {"type": "b", "children": [{"type": "t", "text": "Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605596200"}], "href": "https://doi.org/10.1074/jbc.M605596200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17102137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17102137"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Adam R Leman, Chiaki Noguchi, Candice Y Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.057984"}], "href": "https://doi.org/10.1242/jcs.057984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20124417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20124417"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Si Xie, Oliver Mortusewicz, Hoi Tang Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2015.07.031"}], "href": "https://doi.org/10.1016/j.molcel.2015.07.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26344098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26344098"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Catharina Lavebratt, Louise K Sjöholm, Timo Partonen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PER2 variantion is associated with depression vulnerability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.31021"}], "href": "https://doi.org/10.1002/ajmg.b.31021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19693801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19693801"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Xiaoming Yang, Patricia A Wood, William J M Hrushesky "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.050237"}], "href": "https://doi.org/10.1074/jbc.M109.050237"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19996108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19996108"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Lauren M Young, Antonio Marzio, Pablo Perez-Duran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.09.017"}], "href": "https://doi.org/10.1016/j.celrep.2015.09.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26456830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26456830"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Yong Zhu, Richard G Stevens, Aaron E Hoffman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-0648"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-0648"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19934327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19934327"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Julien N Bianco, Valérie Bergoglio, Yea-Lih Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-08886-8"}], "href": "https://doi.org/10.1038/s41467-019-08886-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30796221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30796221"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Karla V Allebrandt, Maris Teder-Laving, Mahmut Akyol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLOCK gene variants associate with sleep duration in two independent populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2009.12.026"}], "href": "https://doi.org/10.1016/j.biopsych.2009.12.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20149345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20149345"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Danny Halim, Michael P Wilson, Daniel Oliver, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1620507114"}], "href": "https://doi.org/10.1073/pnas.1620507114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28292896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28292896"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Adam R Leman, Jayaraju Dheekollu, Zhong Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Timeless preserves telomere length by promoting efficient DNA replication through human telomeres."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.20810"}], "href": "https://doi.org/10.4161/cc.20810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22672906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22672906"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Leticia K Lerner, Sandro Holzer, Mairi L Kilkenny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Timeless couples G-quadruplex detection with processing by DDX11 helicase during DNA replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2019104185"}], "href": "https://doi.org/10.15252/embj.2019104185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32705708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32705708"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Alan Fu, Derek Leaderer, Tongzhang Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and epigenetic associations of circadian gene TIMELESS and breast cancer risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.20862"}], "href": "https://doi.org/10.1002/mc.20862"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22006848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22006848"}]}]}]}
Synonyms HTIM
Proteins TIM_HUMAN
NCBI Gene ID 8914
API
Download Associations
Predicted Functions View TIMELESS's ARCHS4 Predicted Functions.
Co-expressed Genes View TIMELESS's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View TIMELESS's ARCHS4 Predicted Functions.

Functional Associations

TIMELESS has 8,889 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 126 datasets.

Click the + buttons to view associations for TIMELESS from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of TIMELESS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of TIMELESS gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of TIMELESS gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TIMELESS gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TIMELESS gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of TIMELESS gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of TIMELESS gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of TIMELESS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with TIMELESS protein from the CCLE Cell Line Proteomics dataset.
CellMarker Gene-Cell Type Associations cell types associated with TIMELESS gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of TIMELESS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of TIMELESS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of TIMELESS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of TIMELESS gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
CM4AI U2OS Cell Map Protein Localization Assemblies assemblies containing TIMELESS protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of TIMELESS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing TIMELESS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing TIMELESS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing TIMELESS protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with TIMELESS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with TIMELESS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of TIMELESS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with TIMELESS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with TIMELESS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with TIMELESS gene/protein from the curated CTD Gene-Disease Associations dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with TIMELESS gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with TIMELESS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with TIMELESS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with TIMELESS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with TIMELESS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at TIMELESS gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of TIMELESS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of TIMELESS gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing TIMELESS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with TIMELESS gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with TIMELESS gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of TIMELESS gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with TIMELESS gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing TIMELESS from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of TIMELESS gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of TIMELESS gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of TIMELESS gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of TIMELESS gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of TIMELESS gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of TIMELESS gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving TIMELESS gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving TIMELESS gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving TIMELESS gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing TIMELESS protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing TIMELESS protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing TIMELESS protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by TIMELESS gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by TIMELESS gene from the curated GO Molecular Function Annotations 2023 dataset.
GTEx eQTL 2025 SNPs regulating expression of TIMELESS gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of TIMELESS gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of TIMELESS gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with TIMELESS gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with TIMELESS gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Disease Associations diseases associated with TIMELESS gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with TIMELESS gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of TIMELESS gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of TIMELESS gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of TIMELESS gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of TIMELESS protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for TIMELESS from the curated Hub Proteins Protein-Protein Interactions dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with TIMELESS gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by TIMELESS gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for TIMELESS protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of TIMELESS gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of TIMELESS gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of TIMELESS gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEA Substrates of Kinases kinases that phosphorylate TIMELESS protein from the curated KEA Substrates of Kinases dataset.
Kinase Library Serine Threonine Kinome Atlas kinases that phosphorylate TIMELESS protein from the Kinase Library Serine Threonine Atlas dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of TIMELESS gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of TIMELESS gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with TIMELESS gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of TIMELESS gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of TIMELESS gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of TIMELESS gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of TIMELESS gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
LOCATE Curated Protein Localization Annotations cellular components containing TIMELESS protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain TIMELESS protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by TIMELESS gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting TIMELESS gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of TIMELESS gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by TIMELESS gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Cancer Gene Co-expression Modules co-expressed genes for TIMELESS from the MSigDB Cancer Gene Co-expression Modules dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of TIMELESS gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of TIMELESS gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing TIMELESS protein recovered by IP-MS from the NURSA Protein Complexes dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for TIMELESS from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of TIMELESS gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of TIMELESS gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving TIMELESS protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving TIMELESS protein from the Wikipathways PFOCR 2024 dataset.
PID Pathways pathways involving TIMELESS protein from the PID Pathways dataset.
Reactome Pathways 2024 pathways involving TIMELESS protein from the Reactome Pathways 2024 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of TIMELESS gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of TIMELESS gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TIMELESS gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at TIMELESS gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of TIMELESS gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of TIMELESS gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of TIMELESS gene from the RummaGEO Gene Perturbation Signatures dataset.
Sanger Dependency Map Cancer Cell Line Proteomics cell lines associated with TIMELESS protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of TIMELESS gene from the Sci-Plex Drug Perturbation Signatures dataset.
SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Drugs drug perturbations changing phosphorylation of TIMELESS protein from the SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Drugs dataset.
SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Protein Ligands ligand (protein) perturbations changing phosphorylation of TIMELESS protein from the SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Protein Ligands dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of TIMELESS gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of TIMELESS gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of TIMELESS gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of TIMELESS gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of TIMELESS gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of TIMELESS protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of TIMELESS protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of TIMELESS protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with TIMELESS protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with TIMELESS protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2024 pathways involving TIMELESS protein from the WikiPathways Pathways 2024 dataset.