ULBP3

Chr 6

UL16 binding protein 3

Also known as: N2DL-3, NKG2DL3, RAET1N

NCBI Gene: 79465ENSG00000131019UniProt: Q9BZM4

The protein encoded by this gene is one of several related ligands of the KLRK1/NKG2D receptor, which is found in primary NK cells. Binding of these ligands to the receptor activates several signal transduction pathways, including the JAK2, STAT5, and ERK pathways. The encoded protein is expressed solubly and on the surface of many tumor cells, making it potentially an important target for therapeutics. [provided by RefSeq, Nov 2015]

56
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ULBP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 35 VUS of 56 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 -0.89
OE 1.29 (0.85–1.85)
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.
-0.44Z-score
OE missense 1.11 (0.97–1.27)
148 obs / 133.7 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.1.29 (0.85–1.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.97–1.27)
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.0.99
0≤1.21.6
LoF obs/exp: 14 / 10.8Missense obs/exp: 148 / 133.7Syn Z: 0.03

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
VUS35
Likely Benign3
18
Pathogenic
35
VUS
3
Likely 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
34
1
0
35
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total03619156

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

View in ClinVar →

Protein Context — Lollipop Plot

ULBP3 · 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
Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma.
Wirsching HG et al.·JCI Insight
2019
A monoclonal antibody against human UL16-binding protein 3.
Mao C et al.·Hybridoma (Larchmt)
2012
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
Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies.
Gilhar A et al.·Autoimmun Rev
2016Review
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
Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients.
Akbar S et al.·Front Immunol
2023Cohort
Investigating the susceptibility of treatment-resistant oesophageal tumours to natural killer cell-mediated responses.
Mylod E et al.·Clin Exp Med
2023
Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study.
Lee GH et al.·Yonsei Med J
2021
Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease.
Fernández-Soto D et al.·Front Immunol
2024
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