RAET1E

Chr 6

retinoic acid early transcript 1E

Also known as: LETAL, N2DL-4, NKG2DL4, RAET1E2, RL-4, ULBP4, bA350J20.7

NCBI Gene: 135250ENSG00000164520UniProt: Q8TD07

This gene belong to the RAET1 family, which consists of major histocompatibility complex (MHC) class I-related genes located in a cluster on chromosome 6q24.2-q25.3. This and RAET1G protein differ from other RAET1 proteins in that they have type I membrane-spanning sequences at their C termini rather than glycosylphosphatidylinositol anchor sequences. This protein functions as a ligand for NKG2D receptor, which is expressed on the surface of several types of immune cells, and is involved in innate and adaptive immune responses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2011]

58
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RAET1E
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 35 VUS of 58 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.69LOEUF
pLI 0.000
Z-score -0.09
OE 1.03 (0.63–1.69)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.02Z-score
OE missense 0.99 (0.86–1.15)
138 obs / 138.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.03 (0.63–1.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.86–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 10 / 9.7Missense obs/exp: 138 / 138.8Syn Z: 0.68

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS35
Likely Benign4
19
Pathogenic
35
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
0
0
0
VUS
0
31
4
0
35
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total03523058

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RAET1E · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Immunoprognostic model of lung adenocarcinoma and screening of sensitive drugs.
Liang P et al.·Sci Rep
2022Functional
Transcriptomic analysis of micropapillary high grade T1 urothelial bladder cancer.
Bowden M et al.·Sci Rep
2020
MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer.
Cho H et al.·BMC Cancer
2014
Identification and validation of immune-related gene signature models for predicting prognosis and immunotherapy response in hepatocellular carcinoma.
Liu Z et al.·Front Immunol
2024Functional
Regulation of NKG2D ligand gene expression.
Eagle RA et al.·Hum Immunol
2006
Construction of a prediction model for hepatocellular carcinoma based on machine learning and its prognostic characteristics.
Wang J et al.·Medicine (Baltimore)
2025Functional
Exome analysis reveals differentially mutated gene signatures of stage, grade and subtype in breast cancers.
Li Y et al.·PLoS One
2015
V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.
Valls Serón M et al.·Acta Neuropathol Commun
2016
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.
Antoun A et al.·Hum Immunol
2010
The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients.
Ren S et al.·Stem Cell Res Ther
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools