ULBP2

Chr 6

UL16 binding protein 2

Also known as: ALCAN-alpha, N2DL2, NKG2DL2, RAET1H

NCBI Gene: 80328ENSG00000131015UniProt: Q9BZM5

This gene encodes a major histocompatibility complex (MHC) class I-related molecule that binds to the NKG2D receptor on natural killer (NK) cells to trigger release of multiple cytokines and chemokines that in turn contribute to the recruitment and activation of NK cells. The encoded protein undergoes further processing to generate the mature protein that is either anchored to membrane via a glycosylphosphatidylinositol moiety, or secreted. Many malignant cells secrete the encoded protein to evade immunosurveillance by NK cells. This gene is located in a cluster of multiple MHC class I-related genes on chromosome 6. [provided by RefSeq, Jul 2015]

75
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ULBP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 52 VUS of 75 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.
1.85LOEUF
pLI 0.000
Z-score -0.73
OE 1.26 (0.80–1.85)
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.
-1.36Z-score
OE missense 1.34 (1.18–1.53)
168 obs / 125.0 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.1.26 (0.80–1.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.34 (1.18–1.53)
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.1.05
0≤1.21.6
LoF obs/exp: 12 / 9.6Missense obs/exp: 168 / 125.0Syn Z: -0.25

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS52
Likely Benign2
Benign2
19
Pathogenic
52
VUS
2
Likely Benign
2
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
48
4
0
52
Likely Benign
0
1
0
1
2
Benign
0
2
0
0
2
Total05123175

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

View in ClinVar →

Protein Context — Lollipop Plot

ULBP2 · 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
Machine learning-based diagnostic and prognostic models for breast cancer: a new frontier on the clinical application of natural killer cell-related gene signatures in precision medicine.
Fang Y et al.·Front Immunol
2025Functional
ULBP2 Promotes Tumor Progression by Suppressing NKG2D-Mediated Anti-Tumor Immunity.
Yamane K et al.·Int J Mol Sci
2025
Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis.
Li K et al.·Cancer Immunol Immunother
2009
ITGA1, the alpha 1 subunit of integrin receptor, is a novel marker of drug-resistant senescent melanoma cells in vitro.
Słaby J et al.·Arch Toxicol
2025
Plasma proteins and herpes simplex virus infection: a proteome-wide Mendelian randomization study.
Fu C et al.·Virus Genes
2025
PDT-regulated immune gene prognostic model reveals tumor microenvironment in colorectal cancer liver metastases.
Xu J et al.·Sci Rep
2025Functional
Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses.
D'Angelo A et al.·PLoS One
2023Meta-analysis
Natural killer cell-mediated shedding of ULBP2.
Wang R et al.·PLoS One
2014
UCA1 Inhibits NKG2D-mediated Cytotoxicity of NK Cells to Breast Cancer.
Yin JY et al.·Curr Cancer Drug Targets
2024
NKG2D ligands mediate immunosurveillance of senescent cells.
Sagiv A et al.·Aging (Albany NY)
2016
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