UPB1

Chr 22AR

beta-ureidopropionase 1

Also known as: BUP1

NCBI Gene: 51733 ENSG00000100024 UniProt: Q9UBR1 OMIM: 606673

Beta-ureidopropionase catalyzes the final step in pyrimidine degradation, converting N-carbamoyl-beta-alanine to beta-alanine, ammonia, and carbon dioxide. Mutations cause beta-ureidopropionase deficiency, an autosomal recessive disorder associated with N-carbamyl-beta-amino aciduria and neurological abnormalities. The gene shows low constraint to loss-of-function variation (pLI near zero), consistent with recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.261 OMIM phenotype

Clinical Summary— UPB1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

22 unique Pathogenic / Likely Pathogenic· 123 VUS of 254 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.87Z-score

OE missense 1.16 (1.05–1.29)

261 obs / 224.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.60–1.26)

0≤0.351.4

Missense OE?1.16 (1.05–1.29)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 19 / 22.2Missense obs/exp: 261 / 224.5Syn Z: -1.42

This gene — mechanism propensity

0.6162th %ile

GOF

0.5661th %ile

LOF

0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

254 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic9

VUS123

Likely Benign70

Benign10

Conflicting21

Pathogenic

Likely Pathogenic

123

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	2	0	13
Likely Pathogenic	7	2	0	0	9
VUS	5	94	21	3	123
Likely Benign	0	4	27	39	70
Benign	0	0	5	5	10
Conflicting	—				21
Total	23	100	55	47	246

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 99) ClinVar copy-number / structural variants overlap UPB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →