| Name | retinoic acid early transcript 1L |
| Description | RAET1L belongs to the RAET1 family of major histocompatibility complex (MHC) class I-related genes, which are located within a 180-kb cluster on chromosome 6q24.2-q25.3. The REAT1 genes encode glycoproteins that contain extracellular alpha-1 and alpha-2 domains, but they lack the membrane proximal Ig-like alpha-3 domain. Most RAET1 glycoproteins are anchored to the membrane via glycosylphosphatidylinositol (GPI) linkage (Radosavljevic et al., 2002 [PubMed 11827464]).[supplied by OMIM, Mar 2008] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRAET1L (also known as ULBP6) is a recently characterized, functional member of the RAET1/ULBP family, which serves as a ligand for the activating immunoreceptor NKG2D on natural killer and T-cells. Initial studies demonstrated that RAET1L has a more restricted expression profile than other NKG2D ligands, being detected in specific contexts such as human papillomavirus‐positive cervical carcinoma cell lines and following human cytomegalovirus infection. Moreover, viral immune evasion factors such as UL16 can interact with RAET1L, retaining it intracellularly and thereby modulating its cell surface availability and capacity to induce NK-cell mediated killing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic analyses have revealed that RAET1L is a polymorphic locus, although in some populations its coding regions show a relatively low frequency of nonsynonymous changes. Surveys in distinct ethnic cohorts have documented a handful of single nucleotide polymorphisms in RAET1L, highlighting its variability compared to other NKG2D ligand genes, while further studies have identified allelic variants with notable functional consequences. In particular, one major allele bearing an arginine-to-leucine substitution yields an exceptionally high affinity for NKG2D, leading to strong competitive binding that suppresses NKG2D-mediated cell activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, polymorphisms within the RAET1L gene appear to hold significant immunological relevance. Analysis of transplant cohorts has linked the presence of a specific protective RAET1L*02 allele with improved relapse-free and overall survival following allogeneic stem cell transplantation, implicating RAET1L in the regulation of alloreactive immune responses. In parallel, computational assessments of non-synonymous SNPs in RAET1L suggest that deleterious variants may compromise its interaction with NKG2D, potentially impairing immuno-surveillance against cancer and infections. These findings collectively emphasize the role of RAET1L as not only a mediator of NK-cell activation but also a potential biomarker and therapeutic target in immune modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert A Eagle, James A Traherne, James R Hair, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ULBP6/RAET1L is an additional human NKG2D ligand."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.200939502"}], "href": "https://doi.org/10.1002/eji.200939502"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19658097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19658097"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amornrat V Romphruk, Arunrat Romphruk, Taeko K Naruse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms of NKG2D ligands: diverse RAET1/ULBP genes in northeastern Thais."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunogenetics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00251-009-0394-7"}], "href": "https://doi.org/10.1007/s00251-009-0394-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19688209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19688209"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ayman Antoun, Shirley Jobson, Mark Cook, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single nucleotide polymorphism analysis of the NKG2D ligand cluster on the long arm of chromosome 6: Extensive polymorphisms and evidence of diversity between human populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humimm.2010.02.018"}], "href": "https://doi.org/10.1016/j.humimm.2010.02.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20219610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20219610"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jianmin Zuo, Carrie R Willcox, Fiyaz Mohammed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A disease-linked "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ULBP6"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D ligand binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aai8904"}], "href": "https://doi.org/10.1126/scisignal.aai8904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28559451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28559451"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ayman Antoun, Dhruti Vekaria, Rafik A Salama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The genotype of RAET1L (ULBP6), a ligand for human NKG2D (KLRK1), markedly influences the clinical outcome of allogeneic stem cell transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjh.12072"}], "href": "https://doi.org/10.1111/bjh.12072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23025544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23025544"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Opeyemi S Soremekun, Mahmoud E S Soliman "}, {"type": "b", "children": [{"type": "t", "text": "From genomic variation to protein aberration: Mutational analysis of single nucleotide polymorphism present in ULBP6 gene and implication in immune response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comput Biol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.compbiomed.2019.103354"}], "href": "https://doi.org/10.1016/j.compbiomed.2019.103354"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31302457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31302457"}]}]}]}
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| Synonyms | ULBP6 |
| Proteins | RET1L_HUMAN |
| NCBI Gene ID | 154064 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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RAET1L has 1,542 functional associations with biological entities spanning 8 categories (molecular profile, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 58 datasets.
Click the + buttons to view associations for RAET1L from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of RAET1L 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 RAET1L gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of RAET1L gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of RAET1L gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of RAET1L gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing RAET1L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing RAET1L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with RAET1L 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 RAET1L 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 RAET1L gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with RAET1L gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Disease Associations | diseases associated with RAET1L gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by RAET1L gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Curated Gene-Disease Association Evidence Scores 2025 | diseases involving RAET1L gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores | diseases associated with RAET1L gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with RAET1L 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 RAET1L 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 RAET1L 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 RAET1L gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at RAET1L 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 RAET1L gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of RAET1L gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GAD Gene-Disease Associations | diseases associated with RAET1L gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with RAET1L gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with RAET1L 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 RAET1L from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of RAET1L 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 RAET1L gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving RAET1L gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving RAET1L gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing RAET1L protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing RAET1L protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by RAET1L gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of RAET1L gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of RAET1L gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with RAET1L gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of RAET1L 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 RAET1L 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 RAET1L gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of RAET1L gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with RAET1L gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for RAET1L protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of RAET1L gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of RAET1L gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways 2026 | pathways involving RAET1L protein from the KEGG Pathways 2026 dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of RAET1L gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of RAET1L gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain RAET1L protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of RAET1L gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| Reactome Pathways 2024 | pathways involving RAET1L protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of RAET1L gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at RAET1L gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of RAET1L gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of RAET1L gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of RAET1L gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of RAET1L protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with RAET1L 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 RAET1L protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
