Affinage

CLPTM1L

Lipid scramblase CLPTM1L · UniProt Q96KA5

Length
538 aa
Mass
62.2 kDa
Annotated
2026-06-09
70 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLPTM1L (CRR9) is a multipass integral endoplasmic reticulum membrane protein whose core biochemical activity is lipid scramblase: a genome-wide CRISPR screen identified it as the major scramblase required for efficient GPI-anchored protein biosynthesis, facilitating cytosol-to-lumen lipid translocation across the ER membrane (PMID:35344438), and it participates in a non-canonical GPI-anchoring route that selectively controls surface display of specific GPI-anchored proteins (CD109, CD59, MELTF, MICA*008) through interaction with a free form of PIG-T, an interaction that HCMV US9 antagonizes during infection (PMID:37389656). Beyond this membrane-biogenesis role, CLPTM1L is a determinant of tumor cell survival and chemoresistance: it physically interacts with PI3K and is essential for Ras-induced AKT phosphorylation and anchorage-independent growth, while regulating Bcl-xL through an AKT-independent route (PMID:22675468, PMID:24366883). Under ER stress, including gemcitabine treatment, CLPTM1L relocalizes to the cell surface where its extracellular loop engages GRP78/BiP and p110α to sustain AKT signaling and drive chemoresistance, a node that anti-CLPTM1L antibodies can block (PMID:26939707, PMID:30468251). CLPTM1L can also translocate to the nucleus after irradiation and act as a transcriptional co-activator of estrogen receptor β via an LXXLL motif, inducing CDC25A, c-Jun and BCL2 to confer radioresistance (PMID:32943060), and in nasopharyngeal carcinoma it interacts with ERLIN2 to stabilize SREBP1 against ubiquitination and elevate fatty acid levels (PMID:40550808). In microglia, its scramblase activity drives ferroptosis downstream of an ERK5–NFATC4 transcriptional axis, contributing to ischemic white matter damage (PMID:41512030). Earlier reports placed CLPTM1L at mitochondria and at centrosomes via non-muscle myosin II, where its dysregulation induced aneuploidy (PMID:23300716, PMID:24648346).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 Medium

    Establishing that CRR9/CLPTM1L is a novel conserved multi-transmembrane protein and linking it to cisplatin-induced apoptosis defined the gene as a modulator of drug-induced cell death.

    Evidence 5'RACE cDNA cloning, Northern blot, and transfection with cisplatin sensitivity readout in 2008 ovarian cells

    PMID:11162647

    Open questions at the time
    • No molecular mechanism for the apoptosis link
    • Subcellular localization not yet defined
    • Transfection-overexpression phenotype only
  2. 2012 Medium

    Loss-of-function and rescue experiments showed CLPTM1L acts upstream of Bcl-xL to restrain apoptosis, converting an associative drug-sensitivity link into a defined anti-apoptotic pathway.

    Evidence RNAi knockdown with cisplatin/camptothecin apoptosis assays, Bcl-xL Western blot, and exogenous Bcl-xL rescue in lung tumor cells; separate work localized CLPTM1L-EGFP to mitochondria by fractionation and MitoTracker co-staining with caspase-9/3-7 activation

    PMID:22675468 PMID:23300716

    Open questions at the time
    • How CLPTM1L controls Bcl-xL levels is unresolved
    • Mitochondrial localization later contrasted with ER findings
    • Single lab
  3. 2013 High

    Mechanistic dissection of Ras-driven transformation placed CLPTM1L on the PI3K–AKT survival axis, showing it physically binds PI3K and is required for Ras-induced AKT phosphorylation.

    Evidence RNAi knockdown, transformation/anoikis assays, CLPTM1L–PI3K co-immunoprecipitation, pAKT Western blot, and rescue with constitutively active AKT or Bcl-xL

    PMID:24366883

    Open questions at the time
    • Direct vs indirect nature of the PI3K interaction not structurally defined
    • Bcl-xL regulation shown AKT-independent but its route unknown
  4. 2014 Medium

    ER localization plus an AP-MS interaction with non-muscle myosin II implicated CLPTM1L in cytokinesis and genome stability, broadening its role beyond survival signaling.

    Evidence Immunofluorescence, overexpression growth assays in vitro and xenograft, domain-deletion mutagenesis, affinity purification/mass spectrometry, and aneuploidy assays in pancreatic cancer cells

    PMID:24648346

    Open questions at the time
    • NMM-II interaction not reciprocally validated beyond AP-MS
    • Centrosomal function not linked to scramblase activity
    • Reconciliation with mitochondrial localization absent
  5. 2016 Medium

    Demonstrating cell-surface exposure of CLPTM1L and its gemcitabine-induced binding to p110α revealed a targetable surface node sustaining AKT and chemoresistance.

    Evidence Monoclonal antibody development, flow cytometry for surface CLPTM1L, CLPTM1L–p110α co-IP, pAKT Western blot, anchorage-independent growth, and lung/pancreatic xenograft antibody treatment

    PMID:26939707

    Open questions at the time
    • Mechanism of ER-to-surface trafficking not defined here
    • Single lab antibody reagents
  6. 2019 Medium

    ER stress was identified as the trigger for surface relocalization, where the CLPTM1L extracellular loop engages GRP78 to drive chemoresistance, and CLPTM1L was placed downstream of miR-182 in survival control.

    Evidence CLPTM1L–GRP78 and CLPTM1L–PI3Kα co-IP, surface relocalization imaging, extracellular-loop mutagenesis, antibody inhibition; separately, luciferase reporter validation of miR-182 targeting CRR9 with re-expression rescue in laryngeal carcinoma

    PMID:30468251 PMID:31519771

    Open questions at the time
    • Structural basis of extracellular-loop–GRP78 binding unknown
    • How ER stress drives trafficking mechanistically unresolved
  7. 2020 High

    Identification of an LXXLL motif and irradiation-induced nuclear translocation established a transcriptional co-activator function for CLPTM1L on ERβ target genes, explaining radioresistance.

    Evidence GST pull-down and co-IP (direct ERβ binding via LXXLL), ChIP, luciferase reporters, confocal imaging of nuclear translocation, iTRAQ/microarray, shRNA, and xenograft irradiation models in NSCLC

    PMID:32943060

    Open questions at the time
    • How a multipass ER membrane protein accesses the nucleus is unexplained
    • Relationship between nuclear and scramblase roles unknown
  8. 2021 Medium

    Extracellular vesicle transfer experiments showed CLPTM1L confers chemoresistance in trans via its ectodomain, extending its role to intercellular communication and serum biomarker potential.

    Evidence Exosome isolation and functional transfer, anti-CLPTM1L antibody inhibition, orthotopic isograft and patient-derived xenograft models, and serum detection in ovarian carcinoma

    PMID:33654182

    Open questions at the time
    • Mechanism by which exosomal CLPTM1L acts on recipient cells undefined
    • Single lab
  9. 2022 High

    An unbiased genome-wide CRISPR screen defined the long-sought core biochemical activity of CLPTM1L: a lipid scramblase facilitating cytosol-to-lumen translocation required for GPI biosynthesis.

    Evidence Genome-wide CRISPR screen, functional GPI biosynthesis assays, and transmembrane topology characterization (eight putative TM domains)

    PMID:35344438

    Open questions at the time
    • Lipid substrate specificity not fully defined
    • Link between scramblase activity and cancer survival functions not bridged
    • No high-resolution structure
  10. 2023 High

    Defining a non-canonical GPI-anchoring pathway through a free form of PIG-T explained how CLPTM1L selectively controls a subset of GPI-anchored proteins and how a viral protein hijacks this for immune evasion.

    Evidence CRISPR KO cell lines, flow cytometry of GPI-anchored protein surface expression, CLPTM1L–PIG-T co-IP, and HCMV US9 infection assays

    PMID:37389656

    Open questions at the time
    • Why only specific GPI-anchored proteins depend on CLPTM1L unknown
    • Structural basis of CLPTM1L–PIG-T interaction undefined
  11. 2025 Medium

    In nasopharyngeal carcinoma, CLPTM1L was shown to control lipid metabolism by stabilizing SREBP1 via ERLIN2, with KLF1 driving its transcription, connecting CLPTM1L to fatty acid metabolism.

    Evidence CLPTM1L–ERLIN2 co-IP, ubiquitination assay, KLF1 ChIP on the CLPTM1L promoter, siRNA knockdown, SREBP1 rescue, and in vivo tumor models

    PMID:40550808

    Open questions at the time
    • Whether SREBP1 stabilization depends on scramblase activity unknown
    • Direct vs indirect block of SREBP1 ubiquitination unresolved
  12. 2026 Medium

    Linking Clptm1l scramblase activity to ferroptosis downstream of ERK5–NFATC4 in microglia connected its lipid-handling function to a pathological cell-death program in ischemic white matter damage.

    Evidence Animal white-matter-damage models, genetic and pharmacological ERK5 inhibition, NFATC4 phosphorylation analysis, ferroptosis assays, and cognitive testing

    PMID:41512030

    Open questions at the time
    • Lipid species scrambled to promote ferroptosis not identified
    • Generalizability beyond microglia unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CLPTM1L's single ER-membrane scramblase activity mechanistically gives rise to its diverse PI3K/AKT survival, surface GRP78, nuclear ERβ co-activator, and SREBP1-stabilizing roles remains unresolved.
  • No structure of the channel or its substrate-binding pockets
  • No unifying model linking scramblase activity to signaling/nuclear functions
  • Conflicting localizations (mitochondria, ER, surface, nucleus, centrosome) not reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1 GO:0140110 transcription regulator activity 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Partners
ERLIN2ESR2GRP78MYH9PIG-TPIK3CA

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CRR9 (CLPTM1L) encodes a novel transmembrane protein with multiple transmembrane-like domains, conserved at the C-terminus with human CLPTM1 and homologs in Drosophila and C. elegans. Transfection of CRR9 into cisplatin-sensitive 2008 cells increased sensitivity to cisplatin, indicating CRR9 is associated with cisplatin-induced apoptosis rather than cisplatin resistance per se. Full-length cDNA cloning by 5'RACE, Northern blot, transfection assay with cisplatin sensitivity readout Biochemical and biophysical research communications Medium 11162647
2012 CLPTM1L knockdown in lung tumor cells increased cisplatin- and camptothecin-induced apoptosis proportional to knockdown level, and significantly decreased Bcl-xL protein accumulation. Exogenous Bcl-xL expression rescued sensitization to apoptosis upon CLPTM1L knockdown, placing CLPTM1L upstream of Bcl-xL in the anti-apoptotic pathway. RNAi knockdown, apoptosis assays (cisplatin/camptothecin), Western blot for Bcl-xL, rescue experiment with exogenous Bcl-xL PloS one Medium 22675468
2012 CLPTM1L protein localizes to mitochondria, as demonstrated by co-localization of CLPTM1L-EGFP with the mitochondrial marker MitoTracker and enrichment in mitochondrial versus plasma membrane protein fractions. Knockdown increased cisplatin sensitivity and activated caspase-9 and caspase-3/7. Subcellular fractionation, CLPTM1L-EGFP fluorescence imaging with MitoTracker co-staining, immunohistochemistry, RNAi knockdown, caspase activity assays PloS one Medium 23300716
2013 CLPTM1L is required for Ras-induced lung tumorigenesis: RNAi depletion of CLPTM1L inhibited morphological transformation by H-RasV12 or K-RasV12, anchorage-independent growth, and anoikis resistance. Mechanistically, CLPTM1L physically interacts with phosphoinositide 3-kinase (PI3K) and is essential for Ras-induced AKT phosphorylation. Bcl-xL is regulated by CLPTM1L independently of AKT. Constitutively active AKT or Bcl-xL rescued the transformed phenotype in CLPTM1L-depleted cells. RNAi knockdown, transformation assays (morphology, soft-agar colony formation, anoikis), co-immunoprecipitation (CLPTM1L–PI3K interaction), Western blot for pAKT and Bcl-xL, rescue experiments with constitutively active AKT and Bcl-xL Cancer research High 24366883
2014 CLPTM1L localizes to the endoplasmic reticulum membrane (consistent with multiple predicted transmembrane domains) as shown by immunofluorescence. Overexpression promoted pancreatic cancer cell growth in vitro and in vivo, and this was abrogated by deletion of two hydrophilic domains. Affinity purification/mass spectrometry identified an interaction between CLPTM1L and non-muscle myosin II (NMM-II); the two proteins co-localized in the cytoplasm and, after DNA damage, at centrosomes. Overexpression of CLPTM1L and depletion of NMM-II both induced aneuploidy, suggesting CLPTM1L interferes with NMM-II function in cytokinesis. Immunofluorescence localization, overexpression growth assays (in vitro and xenograft), domain deletion mutagenesis, affinity purification + mass spectrometry, co-localization imaging, aneuploidy assays Cancer research Medium 24648346
2016 CLPTM1L is exposed at the tumor cell surface and can be targeted there. Anti-CLPTM1L monoclonal antibodies inhibited surface accumulation of CLPTM1L, reduced Akt phosphorylation, inhibited anchorage-independent growth, and decreased chemotherapeutic resistance in lung and pancreatic tumor cells. Gemcitabine promoted a physical interaction between CLPTM1L and PI3K p110α in pancreatic cells, which was blocked by anti-CLPTM1L antibodies. In vivo, anti-CLPTM1L treatment inhibited growth of lung and pancreatic adenocarcinoma xenografts. Monoclonal antibody development, flow cytometry for surface CLPTM1L, co-immunoprecipitation (CLPTM1L–p110α), Akt phosphorylation Western blot, anchorage-independent growth assay, xenograft in vivo treatment Molecular cancer therapeutics Medium 26939707
2019 Under ER stress (including gemcitabine treatment), CLPTM1L relocalizes to the cell surface and interacts with GRP78/BiP and PI3K-alpha (p110α). This interaction and surface relocalization is induced by ER stress. The extracellular loop of CLPTM1L is required for gemcitabine resistance and for interaction with GRP78. Inhibition of CLPTM1L with antibodies abrogated GRP78-mediated chemoresistance, anchorage-independent growth, and Akt phosphorylation. Co-immunoprecipitation (CLPTM1L–GRP78 and CLPTM1L–PI3Kα), surface relocalization imaging, extracellular loop deletion/mutagenesis, anti-CLPTM1L antibody functional inhibition, anchorage-independent growth assay, Akt phosphorylation Western blot International journal of cancer Medium 30468251
2019 miR-182 directly targets CRR9 (CLPTM1L) mRNA in laryngeal squamous cell carcinoma cells. Luciferase reporter assay confirmed CRR9 as a direct downstream target of miR-182. Reintroduction of CRR9 reversed miR-182-induced growth inhibition and apoptosis, placing CRR9 downstream of miR-182 in cell survival regulation. Luciferase reporter assay (miR-182 target validation), RT-qPCR and Western blot for CRR9, MTT proliferation assay, Annexin V apoptosis assay, rescue experiment with CRR9 re-expression, in vivo mouse tumor model Bioscience reports Medium 31519771
2020 CLPTM1L acts as a transcriptional co-activator of estrogen receptor β (ERβ) in NSCLC cells by directly interacting with ERβ through an LXXLL nuclear receptor-binding motif. Irradiation induced translocation of CLPTM1L from the cytoplasm into the nucleus. CLPTM1L co-activated ERβ target genes CDC25A, c-Jun, and BCL2. ERβ silencing was sufficient to block CLPTM1L-enhanced radioresistance, and CLPTM1L shRNA combined with irradiation inhibited xenograft tumor growth. Chromatin immunoprecipitation, luciferase reporter gene assay, co-immunoprecipitation, GST pull-down assay (direct interaction via LXXLL motif), immunofluorescence/confocal microscopy (nuclear translocation), iTRAQ proteomics, cDNA microarray, shRNA knockdown, xenograft in vivo model Cell communication and signaling High 32943060
2021 Extracellular vesicle (exosomal) CLPTM1L from cisplatin-resistant ovarian carcinoma cell lines confers cisplatin resistance in trans to drug-sensitive parental cell lines in an ectodomain-dependent fashion. CLPTM1L is present in extracellular vesicle fractions of tumor culture supernatants and in patient serum, increasing upon chemotherapy treatment. Anti-CLPTM1L biologics inhibited both cell-autonomous and intercellular (exosomal) chemoresistance, and re-sensitized resistant cells in orthotopic isograft and patient-derived xenograft models. Exosome isolation and functional transfer assay, anti-CLPTM1L monoclonal antibody inhibition, orthotopic isograft and patient-derived xenograft in vivo models, serum detection of extracellular CLPTM1L NPJ precision oncology Medium 33654182
2022 CLPTM1L is the major lipid scramblase required for efficient glycosylphosphatidylinositol (GPI) biosynthesis in the ER membrane. A genome-wide CRISPR screen identified CLPTM1L as required for GPI biosynthesis. CLPTM1L is an integral membrane protein with eight putative transmembrane domains that facilitates cytosol-to-lumen lipid translocation across the ER membrane, enabling efficient GPI-anchored protein biosynthesis. Genome-wide CRISPR screen, functional GPI biosynthesis assays, characterization of transmembrane topology Proceedings of the National Academy of Sciences of the United States of America High 35344438
2023 CLPTM1L is a component of a non-canonical GPI-anchoring pathway. CLPTM1L is required for surface expression of specific GPI-anchored proteins (CD109, CD59, MELTF, MICA*008) but not others (ULBP2, ULBP3). CLPTM1L's function depends on its interaction with a free form of PIG-T (normally part of the GPI transamidase complex). The HCMV protein US9 inhibits CLPTM1L–PIG-T interaction, thereby downregulating CLPTM1L-dependent GPI-anchored proteins including MICA*008 and MELTF during infection. CRISPR/KO cell lines, flow cytometry for GPI-anchored protein surface expression, co-immunoprecipitation (CLPTM1L–PIG-T interaction), viral infection assays with HCMV US9 The Journal of cell biology High 37389656
2025 CLPTM1L interacts with the lipid raft-associated protein ERLIN2 to cooperatively stabilize SREBP1 protein by inhibiting its ubiquitination, thereby upregulating intracellular free fatty acid levels in NPC cells. The transcription factor KLF1 directly binds the CLPTM1L promoter and drives its transcriptional activation. Knockdown of ERLIN2 or SREBP1 inhibited NPC proliferation and migration synergistically with CLPTM1L depletion; SREBP1 overexpression rescued the inhibitory effects of CLPTM1L and ERLIN2 knockdown. Co-immunoprecipitation (CLPTM1L–ERLIN2 interaction), ubiquitination assay, ChIP assay (KLF1 binding to CLPTM1L promoter), transcriptome analysis, siRNA knockdown, rescue overexpression experiments, in vivo tumor models Cell death & disease Medium 40550808
2026 In microglia, Clptm1l functions as a lipid scramblase involved in ferroptosis downstream of the ERK5–NFATC4 signaling axis. ERK5-mediated phosphorylation of NFATC4 activates Clptm1l transcription, promoting microglial ferroptosis (oxidative stress and lipid peroxidation) that drives ischemic white matter damage. Pharmacological and genetic inhibition of ERK5 reduced Clptm1l-dependent ferroptosis and improved cognitive outcomes. Animal models of white matter damage, genetic and pharmacological ERK5 inhibition, NFATC4 phosphorylation analysis, Clptm1l expression measurement, ferroptosis assays (lipid peroxidation, oxidative stress), cognitive behavioral testing Proceedings of the National Academy of Sciences of the United States of America Medium 41512030

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nature genetics 516 19151717
2011 A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nature genetics 262 22037553
2001 A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochemical and biophysical research communications 127 11162647
2013 Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China. PloS one 106 23555636
2012 Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PloS one 92 22675468
2014 Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. Human molecular genetics 91 25027329
2009 The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis 91 19465454
2011 Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. Journal of medical genetics 64 21617256
2013 CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis. Cancer research 61 24366883
2014 CLPTM1L promotes growth and enhances aneuploidy in pancreatic cancer cells. Cancer research 54 24648346
2012 CLPTM1L is overexpressed in lung cancer and associated with apoptosis. PloS one 50 23300716
2015 A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 48 26545403
2013 Genetic variations in TERT-CLPTM1L locus are associated with risk of lung cancer in Chinese population. Molecular carcinogenesis 45 23908149
2010 Genetic variations in TERT-CLPTM1L genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis 42 20802237
2010 No association between TERT-CLPTM1L single nucleotide polymorphism rs401681 and mean telomere length or cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 40 20570912
2019 CLPTM1L/CRR9 ectodomain interaction with GRP78 at the cell surface signals for survival and chemoresistance upon ER stress in pancreatic adenocarcinoma cells. International journal of cancer 34 30468251
2016 Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma. Scientific reports 32 27185198
2013 Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer--a case-control study in a Chinese population. Lung cancer (Amsterdam, Netherlands) 32 23433592
2021 Targeted biologic inhibition of both tumor cell-intrinsic and intercellular CLPTM1L/CRR9-mediated chemotherapeutic drug resistance. NPJ precision oncology 30 33654182
2014 Genetic polymorphisms of TERT and CLPTM1L, cooking oil fume exposure, and risk of lung cancer: a case-control study in a Chinese non-smoking female population. Medical oncology (Northwood, London, England) 29 25037574
2014 Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk. Human genetics 29 25487306
2022 Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 28 35344438
2020 Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length. Environment international 25 32380304
2013 Significant association of 5p15.33 (TERT-CLPTM1L genes) with lung cancer in Chinese Han population. Experimental lung research 24 23368278
2012 TERT-CLPTM1L polymorphism rs401681 contributes to cancers risk: evidence from a meta-analysis based on 29 publications. PloS one 24 23226346
2011 The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema. The European respiratory journal 24 21622582
2018 The interaction effects of polycyclic aromatic hydrocarbons exposure and TERT- CLPTM1L variants on longitudinal telomere length shortening: A prospective cohort study. Environmental pollution (Barking, Essex : 1987) 23 30097281
2013 Genetic variations in TERT-CLPTM1L genes and risk of lung cancer in Chinese women nonsmokers. PloS one 22 23738012
2014 Multigene pathway-based analyses identify nasopharyngeal carcinoma risk associations for cumulative adverse effects of TERT-CLPTM1L and DNA double-strand breaks repair. International journal of cancer 21 24615621
2014 Genetic variations in TERT-CLPTM1L genes and risk of lung cancer in a Chinese population. Asian Pacific journal of cancer prevention : APJCP 21 24761905
2018 rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations. Carcinogenesis 20 29939218
2013 No association of XRCC1 and CLPTM1L polymorphisms with non-small cell lung cancer in a non-smoking Han Chinese population. Asian Pacific journal of cancer prevention : APJCP 20 24175795
2012 Fine-mapping of a region of chromosome 5p15.33 (TERT-CLPTM1L) suggests a novel locus in TERT and a CLPTM1L haplotype are associated with glioma susceptibility in a Chinese population. International journal of cancer 20 22213090
2016 Novel Anti-CRR9/CLPTM1L Antibodies with Antitumorigenic Activity Inhibit Cell Surface Accumulation, PI3K Interaction, and Survival Signaling. Molecular cancer therapeutics 19 26939707
2014 Association between CLPTM1L polymorphisms (rs402710 and rs401681) and lung cancer susceptibility: evidence from 27 case-control studies. Molecular genetics and genomics : MGG 19 24907075
2016 The identification of two regulatory ESCC susceptibility genetic variants in the TERT-CLPTM1L loci. Oncotarget 18 26716642
2014 Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer: a case-control study in northeast Chinese male population. Medical oncology (Northwood, London, England) 18 24861918
2017 A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus. NPJ genomic medicine 17 28781888
2017 Genetic polymorphisms in the TERT-CLPTM1L region and lung cancer susceptibility in Chinese males. Oncology letters 17 28789383
2014 TERT-CLPTM1L Rs401681 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population. PloS one 16 25007268
2014 CLPTM1L genetic polymorphisms and interaction with smoking and alcohol drinking in lung cancer risk: a case-control study in the Han population from northwest China. Medicine 16 25526467
2016 Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations. Oncotarget 15 26621837
2014 Correlation of CLPTM1L polymorphisms with lung cancer susceptibility and response to cisplatin-based chemotherapy in a Chinese Han population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 25155038
2014 Polymorphisms of TERT and CLPTM1L and the risk of hepatocellular carcinoma in Chinese males. Asian Pacific journal of cancer prevention : APJCP 13 25339005
2022 Cumulative Evidence for Relationships Between Multiple Variants in the TERT and CLPTM1L Region and Risk of Cancer and Non-Cancer Disease. Frontiers in oncology 12 35847915
2016 The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma. Journal of oral science 12 28025427
2014 A genetic sequence variant (GSV) at susceptibility loci of 5p15.33 (TERT-CLPTM1L) is associated with survival outcome in locally advanced and metastatic non-small-cell lung cancer (NSCLC). Lung cancer (Amsterdam, Netherlands) 12 24679952
2015 Genetic variations in the TERT and CLPTM1L gene region and gastrointestinal stromal tumors risk. Oncotarget 11 26372813
2012 Molecular characterization of chromosomal band 5p15.33: a recurrent breakpoint region in mantle cell lymphoma involving the TERT-CLPTM1L locus. Leukemia research 11 23137523
2020 CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells. Cell communication and signaling : CCS 10 32943060
2013 A microduplication of 5p15.33 reveals CLPTM1L as a candidate gene for cleft lip and palate. European journal of medical genetics 10 23395979
2016 CLPTM1L polymorphism as a protective factor for lung cancer: a case-control study in southern Chinese population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 8 26852039
2011 Absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes in a large multicohort study: the HALCyon programme. Aging cell 8 21332924
2014 Association between CLPTM1L-TERT rs401681 polymorphism and risk of pancreatic cancer: a meta-analysis. Clinical and experimental medicine 7 25284078
2023 CLPTM1L expression predicts recurrence of patients with intermediate‑ and high‑risk stage IB‑IIB cervical cancer undergoing radical hysterectomy followed by TP as adjuvant chemotherapy. Oncology letters 6 37545614
2021 CLPTM1L Is a Novel Putative Oncogene Promoting Tumorigenesis in Oral Squamous Cell Carcinoma. Cell transplantation 6 34586883
2019 MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9. Bioscience reports 6 31519771
2019 Polymorphisms of the TERT-CLPTM1L Gene Are Associated with Pharynx-Larynx Cancer. DNA and cell biology 5 31429604
2017 CLPTM1L gene rs402710 (C > T) and rs401681 (C > T) polymorphisms associate with decreased cancer risk: a meta-analysis. Oncotarget 4 29254260
2015 CLPTM1L polymorphism and lung cancer risk. International journal of clinical and experimental medicine 4 26064290
2014 Decreased risk of developing lung cancer in subjects carrying the CLPTM1L rs401681 (G>A) polymorphism: evidence from a meta-analysis. Genetics and molecular research : GMR 3 24634236
2014 Genetic variant in CLPTM1L confers reduced risk of lung cancer: a replication study in Chinese and a meta-analysis. Asian Pacific journal of cancer prevention : APJCP 3 25422207
2023 CLPTM1L is a GPI-anchoring pathway component targeted by HCMV. The Journal of cell biology 2 37389656
2020 TERT-rs33963617 and CLPTM1L-rs77518573 reduce the risk of non-small cell lung cancer in Chinese population. Gene 2 31935503
2025 CLPTM1L interacts with ERLIN2 to stabilize SREBP1 and drive tumorigenesis in nasopharyngeal carcinoma. Cell death & disease 1 40550808
2024 Association of rs401681 (C > T) and rs402710 (C > T) polymorphisms in the CLPTM1L region with risk of lung cancer: a systematic review and meta-analysis. Scientific reports 1 39349641
2023 Exploring the Relationship between CLPTM1L-MS2 Variants and Susceptibility to Bladder Cancer. Genes 1 38254939
2015 Association of CRR9 locus with elevated risk of squamous cell carcinoma and basal cell carcinoma. International journal of clinical and experimental medicine 1 26064272
2026 Erk5-mediated microglial ferroptosis drives ischemic white matter damage via the Nfatc4-Clptm1l axis. Proceedings of the National Academy of Sciences of the United States of America 0 41512030
2019 Assessing a single SNP located at TERT/CLPTM1L multi-cancer risk region as a genetic modifier for risk of pancreatic cancer and melanoma in Dutch CDKN2A mutation carriers. Familial cancer 0 31203567

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