UPB1

Chr 22AR

beta-ureidopropionase 1

Also known as: BUP1

NCBI Gene: 51733ENSG00000100024UniProt: Q9UBR1

This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Beta-ureidopropionase deficiencyMIM #613161
AR
350
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UPB1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 167 VUS of 350 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.
1.26LOEUF
pLI 0.000
Z-score 0.63
OE 0.86 (0.60–1.26)
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.
-0.87Z-score
OE missense 1.16 (1.05–1.29)
261 obs / 224.5 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.0.86 (0.60–1.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.16 (1.05–1.29)
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.1.19
0≤1.21.6
LoF obs/exp: 19 / 22.2Missense obs/exp: 261 / 224.5Syn Z: -1.42

ClinVar Variant Classifications

350 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic20
VUS167
Likely Benign71
Benign11
Conflicting23
49
Pathogenic
20
Likely Pathogenic
167
VUS
71
Likely Benign
11
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
42
0
49
Likely Pathogenic
6
2
12
0
20
VUS
4
91
69
3
167
Likely Benign
0
4
28
39
71
Benign
0
0
6
5
11
Conflicting
—23
Total179715747341

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

View in ClinVar →

Protein Context — Lollipop Plot

UPB1 · 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

Beta-ureidopropionase deficiency

MIM #613161

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The relationship between beta-ureidopropionase deficiency due to UPB1 variants and human phenotypes is uncertain.
Righetti S et al.·Mol Genet Metab
2022
β-Ureidopropionase deficiency due to novel and rare UPB1 mutations affecting pre-mRNA splicing and protein structural integrity and catalytic activity.
Dobritzsch D et al.·Mol Genet Metab
2022
Contribution of the β-ureidopropionase (UPB1) gene alterations to the development of fluoropyrimidine-related toxicity.
Fidlerova J et al.·Pharmacol Rep
2012
Impact of DPYD, DPYS, and UPB1 gene variations on severe drug-related toxicity in patients with cancer.
Yokoi K et al.·Cancer Sci
2020Cohort
Clinical and genetic analysis of 7 Chinese patients with β-ureidopropionase deficiency.
Fang Y et al.·Medicine (Baltimore)
2019Cohort
An exome array study of the plasma metabolome.
Rhee EP et al.·Nat Commun
2016
Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma.
Kunicka T et al.·BMC Cancer
2016
Clinical efficacy and gene chip expression analysis of Shenzhu Guanxin recipe granules in patients with intermediate coronary lesions.
Xiao J et al.·J Tradit Chin Med
2024Cohort
Identification of a novel synonymous mutation in the human β -Ureidopropionase Gene UPB1 affecting pre-mRNA splicing.
Meijer J et al.·Nucleosides Nucleotides Nucleic Acids
2013Case report
ß-ureidopropionase deficiency: phenotype, genotype and protein structural consequences in 16 patients.
van Kuilenburg AB et al.·Biochim Biophys Acta
2012Cohort
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