RAET1G

Chr 6

retinoic acid early transcript 1G

Also known as: ULBP5

NCBI Gene: 353091ENSG00000203722UniProt: Q6H3X3

This gene encodes a member of the major histocompatibility complex (MHC) class I family of proteins. Although the encoded protein includes C-terminal transmembrane and cytoplasmic domains, proteolytic processing results in the removal of these domains and subsequent tethering to the plasma membrane by a glycosylphosphatidylinositol (GPI)-anchor. The encoded protein is one of several related ligands of the natural killer group 2, member D (NKG2D) receptor, which functions as an activating receptor in innate and adaptive immunity. This gene is present in a gene cluster on chromosome 6. [provided by RefSeq, Jul 2015]

69
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RAET1G
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 47 VUS of 69 total submissions

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.
1.38LOEUF
pLI 0.000
Z-score 0.64
OE 0.80 (0.48–1.38)
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.
-0.32Z-score
OE missense 1.07 (0.95–1.21)
189 obs / 176.8 exp
Tolerant

Tolerant to missense variation

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.0.80 (0.48–1.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.95–1.21)
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.1.26
0≤1.21.6
LoF obs/exp: 9 / 11.3Missense obs/exp: 189 / 176.8Syn Z: -1.73

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS47
Likely Benign3
19
Pathogenic
47
VUS
3
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
43
4
0
47
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total04623069

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

View in ClinVar →

Protein Context — Lollipop Plot

RAET1G · 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
Linkage disequilibrium of polymorphic RAET1 genes in Thais.
Rareongjai S et al.·Tissue Antigens
2010
Polymorphisms of NKG2D ligands: diverse RAET1/ULBP genes in northeastern Thais.
Romphruk AV et al.·Immunogenetics
2009
NKG2D Receptor and Its Ligands in Host Defense.
Lanier LL·Cancer Immunol Res
2015Review
Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
Eagle RA et al.·PLoS One
2009
Differential NKG2D binding to highly related human NKG2D ligands ULBP2 and RAET1G is determined by a single amino acid in the alpha2 domain.
Wittenbrink M et al.·Eur J Immunol
2009
Post-translational modification of the NKG2D ligand RAET1G leads to cell surface expression of a glycosylphosphatidylinositol-linked isoform.
Ohashi M et al.·J Biol Chem
2010
MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer.
Cho H et al.·BMC Cancer
2014
Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D.
Bacon L et al.·J Immunol
2004
RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity.
Cao W et al.·J Biol Chem
2007
Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes.
Shin S et al.·Cancer Genomics Proteomics
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools