ULBP1

Chr 6

UL16 binding protein 1

Also known as: N2DL-1, NKG2DL1, RAET1I

NCBI Gene: 80329ENSG00000111981UniProt: Q9BZM6

The protein encoded by this gene is a ligand of natural killer group 2, member D (NKG2D), an immune system-activating receptor on NK cells and T-cells. Binding of the encoded ligand to NKG2D leads to activation of several signal transduction pathways, including those of JAK2, STAT5, ERK and PI3K kinase/Akt. Also, in cytomegalovirus-infected cells, this ligand binds the UL16 glycoprotein and is prevented from activating the immune system. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

86
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ULBP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 53 VUS of 86 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.
1.52LOEUF
pLI 0.000
Z-score 0.30
OE 0.90 (0.56–1.52)
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.
-1.22Z-score
OE missense 1.31 (1.15–1.49)
162 obs / 123.7 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.0.90 (0.56–1.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.31 (1.15–1.49)
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.1.36
0≤1.21.6
LoF obs/exp: 10 / 11.1Missense obs/exp: 162 / 123.7Syn Z: -1.93

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
VUS53
Likely Benign8
Benign7
18
Pathogenic
53
VUS
8
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
0
0
0
VUS
0
49
4
0
53
Likely Benign
0
7
0
1
8
Benign
1
4
0
2
7
Total16022386

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

View in ClinVar →

Protein Context — Lollipop Plot

ULBP1 · 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
Designs of NKG2D-based immunotherapeutics for cancer.
Han J et al.·Front Immunol
2025Review
Xenogeneic transplantation and tolerance in the era of CRISPR-Cas9.
Cowan PJ et al.·Curr Opin Organ Transplant
2019Review
MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer.
Cho H et al.·BMC Cancer
2014
Natural killer cell-mediated shedding of ULBP2.
Wang R et al.·PLoS One
2014
B7H6 is the predominant activating ligand driving natural killer cell-mediated killing in patients with liquid tumours: evidence from clinical, in silico, in vitro, and in vivo studies.
Lee S et al.·EBioMedicine
2024Cohort
Investigation and verification of the clinical significance and perspective of natural killer group 2 member D ligands in colon adenocarcinoma.
Ruan GT et al.·Aging (Albany NY)
2021
The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity.
Lança T et al.·Blood
2010
Expression of NKG2D ligands is downregulated by β-catenin signalling and associates with HCC aggressiveness.
Cadoux M et al.·J Hepatol
2021
NK cells limit the synergistic anti-tumor effect of PD-1 inhibition and βγ-biased IL-2.
Jiang H et al.·Int J Biol Macromol
2025
[An immunological approach to acute myeloid leukaemia].
González B et al.·An Pediatr (Barc)
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cyclosporin A indirectly suppresses NK cells activity in renal microvascular inflammation by inducing ubiquitination-dependent degradation of ULBP1.
Ma J et al.·Int Immunopharmacol
2026
Temozolomide and the PARP Inhibitor Niraparib Enhance Expression of Natural Killer Group 2D Ligand ULBP1 and Gamma-Delta T Cell Cytotoxicity in Glioblastoma.
Jones AB et al.·Cancers (Basel)
2024🔓 Open Access
The HHV-6B U20 glycoprotein binds ULBP1, masking it from recognition by NKG2D and interfering with natural killer cell activation.
Weaver GC et al.·Front Immunol
2024🔓 Open Access
Dynamics of Soluble Forms of the Immune Checkpoint Components PD-1/PD-L1/B7-H3, CD314/ULBP1, and HLA-G in Peripheral Blood of Melanoma Patients Receiving Blockers of Programmed Cell Death Protein PD-1.
Gershtein ES et al.·Bull Exp Biol Med
2023Cohort
Immune ULBP1 is Elevated in Colon Adenocarcinoma and Predicts Prognosis.
Ruan GT et al.·Front Genet
2022🔓 Open Access
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