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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RAET1G
retinoic acid early transcript 1G
Chromosome 6 · 6q25.1
NCBI Gene: 353091Ensembl: ENSG00000203722.9HGNC: HGNC:16795UniProt: Q6H3X3
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
natural killer cell lectin-like receptor bindingplasma membranepositive regulation of natural killer cell cytokine productionprotein bindingneoplasmhepatocellular carcinomapsoriasishereditary spastic paraplegia
✦AI Summary

RAET1G (retinoic acid early transcript 1G) is an NKG2D ligand that activates natural killer cell immunity. RAET1G encodes a class I-like MHC-related glycoprotein with structural features distinct from other ULBP family members 1. The protein exists as two isoforms: a full-length transmembrane form (RAET1G1) primarily retained intracellularly, and a truncated soluble form (RAET1G2) that can be secreted 2. RAET1G binds weakly to the NKG2D receptor compared to related ULBP2, with differential binding determined by a single amino acid substitution in the alpha2 domain 3. This reduced avidity results in less efficient NKG2D downregulation and NK cell degranulation 3. RAET1G is broadly expressed across tissues but shows particularly elevated expression in epithelial cancers and inflammatory conditions like celiac disease 2. Post-translational modification can generate a GPI-anchored isoform at the cell surface 4. Clinically, RAET1G expression exhibits opposing prognostic significance: in cervical cancer, elevated RAET1G expression correlates with shorter disease-free survival 5. RAET1G exists with population-specific polymorphisms that show linkage disequilibrium with other RAET1 genes 67. As an NKG2D ligand, RAET1G participates in immune surveillance of stressed, transformed, and pathogen-infected cells 8.

Sources cited
1
RAET1G binds weakly to NKG2D due to amino acid substitution in alpha2 domain, resulting in less efficient NK degranulation
PMID: 19424970
2
RAET1G shows genetic polymorphisms and linkage disequilibrium with other RAET1 genes in Thai populations
PMID: 20522206
3
RAET1G exists as two isoforms with different cellular localization and function; full-length form retained intracellularly, truncated form secreted
PMID: 19223974
4
RAET1G is a transmembrane NKG2D ligand with population-specific polymorphisms in exons 2 and 3
PMID: 19688209
5
RAET1G is one of eight human NKG2D ligands serving as mechanism to detect cellular stress, infection, and transformation
PMID: 26041808
6
RAET1G expression correlates with shorter disease-free survival in cervical cancer patients
PMID: 25510288
7
RAET1G undergoes post-translational C-terminal cleavage and can be modified to GPI-anchored form at cell surface
PMID: 20304922
8
RAET1G is a transmembrane NKG2D ligand with class I-like alpha1 and alpha2 domains, capable of binding NKG2D and human CMV protein UL16
PMID: 15240696
Disease Associationsⓘ20
neoplasmOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
psoriasisOpen Targets
0.01Suggestive
hereditary spastic paraplegiaOpen Targets
0.01Suggestive
Henoch-Schoenlein purpuraOpen Targets
0.01Suggestive
papillary thyroid carcinomaOpen Targets
0.01Suggestive
cervical cancerOpen Targets
0.01Suggestive
small cell lung carcinomaOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
cervical squamous intraepithelial neoplasiaOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
celiac diseaseOpen Targets
0.00Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.00Suggestive
Invasive Breast CarcinomaOpen Targets
0.00Suggestive
sarcomaOpen Targets
0.00Suggestive
cervical intraepithelial neoplasiaOpen Targets
0.00Suggestive
lung carcinomaOpen Targets
0.00Suggestive
colorectal cancerOpen Targets
0.00Suggestive
colorectal neoplasmOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MICBProtein interaction100%KLRK1Protein interaction100%KLRC4-KLRK1Protein interaction100%RAET1LProtein interaction80%RAET1EProtein interaction76%ULBP3Shared pathway67%
Tissue Expression6 tissues
Ovary
100%
Lung
42%
Heart
27%
Liver
21%
Brain
10%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
RAET1GMICBKLRK1KLRC4-KLRK1RAET1LRAET1EULBP3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q6H3X3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.16LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.60–1.16]
RankingsWhere RAET1G stands among ~20K protein-coding genes
  • #13,501of 20,598
    Most Researched23
  • #12,079of 17,882
    Most Constrained (LOEUF)1.16
Genes detectedRAET1G
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Differential NKG2D binding to highly related human NKG2D ligands ULBP2 and RAET1G is determined by a single amino acid in the alpha2 domain.
PMID: 19424970
Eur J Immunol · 2009
1.00
2
Linkage disequilibrium of polymorphic RAET1 genes in Thais.
PMID: 20522206
Tissue Antigens · 2010
0.90
3
Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
PMID: 19223974
PLoS One · 2009
0.80
4
Polymorphisms of NKG2D ligands: diverse RAET1/ULBP genes in northeastern Thais.
PMID: 19688209
Immunogenetics · 2009
0.70
5
NKG2D Receptor and Its Ligands in Host Defense.
PMID: 26041808
Cancer Immunol Res · 2015
0.60