UBN1

Chr 16

ubinuclein 1

Also known as: VT, VT4

NCBI Gene: 29855ENSG00000118900UniProt: Q9NPG3

Cellular senescence is a hallmark of tumor suppression and tissue aging. Senescent cells contain domains of heterochromatin, called senescence-associated heterochromatin foci (SAHF), that repress proliferation-promoting genes. The protein encoded by this gene binds to proliferation-promoting genes and is required for SAHF formation, enhancing methylation of histone H3. [provided by RefSeq, Oct 2016]

48
ClinVar variants
27
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— UBN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 8 VUS of 48 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.21LOEUF
pLI 1.000
Z-score 5.89
OE 0.10 (0.05–0.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
-0.79Z-score
OE missense 1.09 (1.02–1.16)
691 obs / 635.0 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.0.10 (0.05–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (1.02–1.16)
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.1.24
0≤1.21.6
LoF obs/exp: 5 / 49.9Missense obs/exp: 691 / 635.0Syn Z: -3.14

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS8
Likely Benign4
Benign9
26
Pathogenic
1
Likely Pathogenic
8
VUS
4
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
1
0
0
1
VUS
0
0
8
0
8
Likely Benign
0
0
0
4
4
Benign
0
3
1
5
9
Total0435948

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

View in ClinVar →

Protein Context — Lollipop Plot

UBN1 · 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
UBINUCLEIN 1; UBN1
MIM #609771 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prioritization of predisposition genes for familial non-medullary thyroid cancer by whole-genome sequencing.
Srivastava A et al.·Eur J Endocrinol
2025
Structural insights into the interaction of Hir2 and Hpc2 in the yeast Hir histone chaperone complex.
Tseng CH et al.·Structure
2025
Identification of an ubinuclein 1 region required for stability and function of the human HIRA/UBN1/CABIN1/ASF1a histone H3.3 chaperone complex.
Tang Y et al.·Biochemistry
2012
Placing the HIRA histone chaperone complex in the chromatin landscape.
Pchelintsev NA et al.·Cell Rep
2013
Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex.
Rai TS et al.·Mol Cell Biol
2011Functional
HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding.
Vogt A et al.·J Biol Chem
2024
HIRA contributes to zygote formation in mice and is implicated in human 1PN zygote phenotype.
Smith R et al.·Reproduction
2021
Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.
Ray-Gallet D et al.·Nat Commun
2018Functional
A Molecular Prospective for HIRA Complex Assembly and H3.3-Specific Histone Chaperone Function.
Ricketts MD et al.·J Mol Biol
2017Review
Ubinuclein, a novel nuclear protein interacting with cellular and viral transcription factors.
Aho S et al.·J Cell Biol
2000
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