UBN1

Chr 16

ubinuclein 1

Also known as: VT, VT4

NCBI Gene: 29855 ENSG00000118900 UniProt: Q9NPG3 OMIM: 609771

The protein encoded by UBN1 regulates chromatin assembly and formation of senescence-associated heterochromatin foci that repress proliferation-promoting genes. Mutations cause autosomal dominant intellectual disability with microcephaly and seizures, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.21), indicating that haploinsufficiency is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— UBN1

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic of 45 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

-0.79Z-score

OE missense 1.09 (1.02–1.16)

691 obs / 635.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.21)

0≤0.351.4

Missense OE?1.09 (1.02–1.16)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 5 / 49.9Missense obs/exp: 691 / 635.0Syn Z: -3.14

This gene — mechanism propensity

0.3097th %ile

GOF

0.2796th %ile

LOF

0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

Likely Benign4

Benign9

Likely Pathogenic

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	0	0	0	0
Likely Benign	0	0	4	4
Benign	3	1	5	9
Total	4	1	9	14

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap UBN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →