UBP1

Chr 3

upstream binding protein 1

Also known as: LBP-1B, LBP-1a, LBP1A, LBP1B, TFCP2L5

NCBI Gene: 7342 ENSG00000153560 UniProt: Q9NZI7

The protein functions as a transcriptional activator that regulates RNA polymerase II transcription, including modulation of alpha-globin gene expression in erythroid cells and repression of HIV-1 transcription. UBP1 is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.088), suggesting that mutations would likely cause severe developmental phenotypes. However, no specific genetic disorders have been definitively associated with UBP1 mutations in current databases.

ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of viral transcription and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.09

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 5.39

OE 0.00 (0.00–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.99Z-score

OE missense 0.52 (0.45–0.59)

155 obs / 300.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.09)

0≤0.351.4

Missense OE?0.52 (0.45–0.59)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 0 / 33.8Missense obs/exp: 155 / 300.7Syn Z: 0.88

Background carrier burden — how many people carry a rare variant somewhere in UBP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

469 rare PASS variants

Rare truncating (LoF)

1 in 5,500

60 rare PASS variants

Rare synonymous (reference)

1 in 210

233 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UBP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 6,700
South Asian	~43k	1 in 160	1 in 6,100
Remaining (unassigned)	~30k	1 in 140	1 in 980
European (Finnish)	~27k	1 in 570	1 in 2,400
Admixed American	~22k	1 in 210	≈ 1 in 11,000
African / African American	~21k	1 in 200	≈ 1 in 10,000
East Asian	~20k	1 in 290	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 450	none seen
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓